REVIEW

Annual review of selected scientific literature: A report of the ]]

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Committee on Scientific Investigation of the American Academy

of Restorative Dentistry
David R. Cagna, DMD, MS,a Terence E. Donovan, DDS,b James R. McKee, DDS,c Frederick Eichmiller, DDS,d
James E. Metz, DDS,e Riccardo Marzola, DDS,f Kevin G. Murphy, DDS, MS,g and
Matthias Troeltzsch, MD, DMD, PhDh,i

PROSTHODONTICS ABSTRACT
The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers
The 2022 professional litera­ this review of the 2022 dental literature to briefly touch on several topics of interest to modern
ture pertinent to the clinical restorative dentistry. Each committee member brings discipline-specific expertise in their subject
practice of prosthodontics areas that include (in order of the appearance in this report): prosthodontics; periodontics, alveolar
was voluminous and well bone, and peri-implant tissues; dental materials and therapeutics; occlusion and temporomandibular
disorders; sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery;
beyond the capacity for any
and dental caries and cariology. The authors focused their efforts on reporting information likely
single article to encompass. to influence the daily dental treatment decisions of the reader with an emphasis on innovations,
That said, the attempt is new materials and processes, and future trends in dentistry. With the tremendous volume of
made here to identify a literature published daily in dentistry and related disciplines, this review cannot be
broad distribution of reports comprehensive. Instead, its purpose is to update interested readers and provide valuable
that will permit dental clin­ resource material for those willing to subsequently pursue greater detail on their own. Our
icians, academicians, scien­ intent remains to assist colleagues in navigating the tremendous volume of newly minted
information produced annually. Finally, we hope that readers find this work helpful in managing
tists, dental students, and
patients. (J Prosthet Dent 2023;130:453-532)
dental residents a glimpse
into the developments, trends, and innovations im­ dentures, conventional fixed prosthodontics, general
pacting the practice of modern prosthodontics. implant prosthodontic considerations, implant re­
Therefore, important articles strategically selected movable prosthodontics, implant fixed prosthodon­
from the review of well over 50 professional journals tics, and prosthodontic materials.
were included to update readers in 8 categories: In addition to articles selected for detailed review, many
general prosthodontic considerations, conventional excellent narrative reviews, systematic reviews, meta-ana­
complete dentures, conventional removable partial lyses, and helpful clinical descriptive reports were also

Declarations of interest: The authors have no interests to declare.

a
Professor, Associate Dean, Chair, and Residency Director, Department of Prosthodontics, University of Tennessee Health Sciences Center College of Dentistry, Memphis,
Tenn.
b
Professor, Department of Comprehensive Oral Health, University of North Carolina School of Dentistry, Chapel Hill, NC.
c
Private practice, Restorative Dentistry, Downers Grove, Ill.
d
Vice President and Science Officer (Emeritus), Delta Dental of Wisconsin, Stevens Point, Wis.
e
Private practice, Restorative Dentistry, Columbus, Ohio.
f
Private practice, Prosthodontics, Ferrara, Italy.
g
Associate Clinical Professor, Department of Periodontics, University of Maryland College of Dentistry, Baltimore, Md.
h
Private practice, Oral, Maxillofacial, and Facial Plastic Surgery, Ansbach, Germany.
i
Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilian University of Munich
(LMU), Munich, Germany.

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454
published, addressing issues important to the practice of
prosthodontics. Although it is impractical to provide a de­
tailed analysis of this entire body of information, the se­
lected articles are listed here, by topic area, for the reader’s
convenience and consumption: anatomy and physiology,1,2
bruxism,3-5 conventional complete dentures,6 conventional
fixed prosthodontics,7-14 conventional removable partial
dentures,15-18 dental hygiene,19 dental wear,20-22 digital
dentistry and artificial intelligence,23-28 digital dentistry de­
sign and manufacturing,29-37 endo-restorative dentistry,38-42
esthetics,43-46 evidence-based dentistry,47,48 implant com­
plications,49-56 implant esthetics,57 implant fixed prostho­
dontics,58-63 implant removable prosthodontics,64-67 implant
surgery,68,69 implant treatment planning,70-73 im­
pressions,74-77 material science,78-83 maxillofacial prosthe­
tics,84-88 mechanics/biomechanics,89-91 occlusion, jaw
relations, and articulation,92-95 osseointegration,96,97 pa­
thology, disease, and disorders,98-106 pediatric restorative
dentistry,107,108 peri-implant tissues,109-116 periodontics-re­
storative dentistry,117 pharmacology,118-123 sleep-related
breathing disorders,124 TMD and orofacial pain,125-129 and
miscellaneous prosthodontic-related topics.130-134
In January 2022, the Journal of Prosthetic Dentistry
published the first edition of JPD Digital: A Multimedia
Resource. This innovative video resource expands exposure
to important prosthodontic topics across multiple media
platforms. High-quality video presentations were made
freely available. This resource is exceptional and should be
visited by all interested readers. Topics included subtractive
manufacturing of conventional complete dentures,135 digital
workflows for printed surgical guides,136 maxillofacial
prosthetics,137 robot-assisted dental implant surgery,138 di­
gital workflows for complete arch implant therapy,139 digital
shade calibration,140 fixed prosthodontic workflows,141 the
removal of integrated dental implants,142 and cone beam
computed tomography.143
Four articles of interest will be considered before
venturing into categorical reviews. The first two articles
address our attempts to better appreciate the complex
psychological factors involved with routinely managing
prosthodontic patients.
The loss of any body part can be associated with
psychological morbidity, decreased well-being, and body
image disturbance. This morbidity is demonstrated in
dentistry as patients experience two potentially traumatic
events, edentulism and wearing complete dentures.
Kudsi et al144 investigated the psychological morbidities
associated with tooth loss despite treatment with tech­
nically successful dentures to better understand specific
etiologic factors contributing to this loss of well-being.
This cross-sectional questionnaire-based study
compared the psychologic and functional status of 2
patient groups: individuals with tooth loss who wore
optimal-quality removable complete dentures (denture
group; n=70) and those with tooth loss who did not
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Volume 130 Issue 4
wear dentures (control group; n=68). The initial ques­
tionnaire assessed the psychological impact of tooth loss
and denture wear. A second questionnaire assessed
personality traits, including anxiety, depression, stress,
body image impairment, and functional difficulties.
The results indicated a significant difference in body
image dissatisfaction between the groups (χ2=7.72;
P=.005). The denture group had a 5.75-times higher
probability than the control group of suffering from body
image disturbance. Older patients were predicted to
have 75% less likelihood of body image disturbance
(OR=.25), and men were expected to have up to 70%
less disorder (OR=.3) than women. As for psychological
morbidities, participants in both groups presented with
somatic symptoms related to depression (15.7%) and
anxiety (7.8%), nearly double that expected in the gen­
eral population. Furthermore, participants complaining
about body image impairment were more likely to have
higher neuroticism scores (OR=3.64).
The authors concluded that tooth loss and the pro­
vision of technically sound conventional complete den­
tures could be associated with body image
dissatisfaction and psychological morbidity. They sug­
gested that providing patient-centered care, rather than
simply managing dental problems, is paramount before
extracting teeth and providing restorative therapy.
An opinion piece authored by Garg and Klineberg145
reviewed edentulism and currently available treatment
options. The capacity to function with conventional
complete dentures varies with patient adaptability and
psychological acceptance of the treatment. In part, sa­
tisfaction with conventional removable prostheses varies
due to available dental implant options. Quality-of-life
studies have suggested the advantages of implant
therapy, particularly concerning improved function and
esthetics. Osseoperception (sensorimotor feedback from
peri-implant tissues) may enhance function with im­
plant treatment. It is recognized that tooth loss and the
loss of periodontal mechanoreceptors have a detri­
mental effect on jaw motor control even after implant
treatment. Despite this limitation, the authors suggested
oral rehabilitation with or without implants improves
function and esthetics and helps maintain psychosocial
and cognitive health.
The last two articles of interest will only be briefly
mentioned here. Interested readers are encouraged to
review these publications directly. Armijo-Olivo et al146
provided a clinical significance review in rehabilitation
research. Given the limitations of statistical significance
in delivering meaningful results for practicing clin­
icians, the clinical-based interpretations of research
outcomes and the report of clinical relevance in inter­
vention trials should be a priority. The authors re­
commended using distribution-based, anchor-based,
and opinion-based reporting methods. Implementation
Cagna et al
October 2023
of research results in clinical practice should be an
objective.
Finally, Mikelis et al147 reviewed the literature to
address publication bias in dentistry's randomized con­
trolled trials (RCTs). Without going into detail here, their
findings indicated that many dental journals are biased
in the preferential publication of outcomes considered
“successful” and statistically significant. In addition,
clinical trial registration (a formal standardized declara­
tion of the methodology and outcomes under in­
vestigation) was routinely lacking. Finally, published
reports from countries in Asia and from other non-
European or non-American countries were associated
with statistically significant primary outcomes.
The publication of research findings from dental
RCTs is driven by the beliefs of authors, reviewers, and
editors regarding what is interesting, attractive, sig­
nificant, and essential to their readers. In contrast,
publication strategies based on transparent and valid
experimental design, methodology, and reporting seem
less critical.
General prosthodontics
Personal and professional management of periodontally
compromised teeth is challenging. The decision of when
and if periodontally compromised teeth should be
treated or extracted is complex on many levels. Clinical
decisions are too often based on the dentist’s experience,
training, or the patient’s personal preference and so­
cioeconomic status rather than on sound clinical scien­
tific evidence and known risk factors.
Using a systematic approach to assess existing lit­
erature on the subject, the focused population, inter­
vention, control, outcome (PICO) question posed by
Sarafidou et al148 was, “Concerning biological, func­
tional, esthetic, and technical complications, does the
extraction and prosthodontic replacement of period­
ontally compromised teeth yield better outcomes when
compared to tooth preservation using periodontal
treatment and regenerative therapy?”
A systematic search was conducted for studies re­
porting a minimum of 5-year follow-up, with outcomes
based on clinical and radiographic data and the incidence
of tooth and implant loss. Only RCTs, cohort studies, and
case series with prospective designs were included.
The initial search identified 1080 articles. Further
screening yielded 24 publications for inclusion in this
systematic review. Twenty studies reported on the
treatment provided for natural teeth, including non­
surgical and surgical periodontal therapy with or
without regeneration procedures. Three studies involved
extracting periodontally compromised teeth, implant
placement with or without bone and soft tissue aug­
mentation, and restoration with fixed prostheses. Only 1
Cagna et al
455
study directly compared the two treatment modalities.
In addition, there were 11 RCTs and 13 prospective in­
vestigations.
The results indicated a survival rate range of 81.8% to
100% for the natural tooth group and 94.8% to 100% for
the extraction/implant group. In addition, 76.09% of the
implant-supported restorations were complication-free
over the follow-up period, while 86.83% of the natural
tooth-supported restorations survived without compli­
cation. Failure rates were similar in both study groups,
including 68 (4.79%) implants and 32 (4.48%) teeth lost
during the follow-up period.
Unfortunately, protocol heterogeneity prohibited
meta-analysis. Additionally, the potential for risk of
bias149 was determined to be high or unclear in many of
the included studies, particularly concerning perfor­
mance bias and allocation concealment.
The authors concluded that, in periodontitis-sus­
ceptible patients, both treatment modalities present high
survival rates. Applying bone regeneration techniques
followed by rigorous maintenance improves the long-
term prognosis of periodontally involved teeth.
Therefore, appropriate management of natural teeth can
offer a viable alternative for several years before ex­
traction and implant replacement. More well-designed
RCTs are needed to permit definite conclusions on this
subject.
Computer-aided design and computer-aided manu­
facturing (CAD-CAM) methods affect the clinical out­
comes of single crowns produced using digital workflows.
These restorations are often designed and manufactured
using chairside digital workflows. However, little is
known about the digital restoration accuracy created by
dentists with varying clinical and CAD experience levels
within a chairside workflow. Therefore, No-Cortes et al150
sought to compare the accuracy of single crown digital
design between dentists with different levels of CAD and
clinical prosthodontics expertise.
This in vitro study involved 2 dental study casts con­
taining 12 teeth prepared for single crowns (3 in the
anterior maxilla, 4 in the posterior maxilla, and 5 in the
posterior mandible). The casts were scanned and saved as
standard tessellation language (STL) files, then exported
to a CAD software program (Meshmixer, Autodesk). Four
dentists (2 clinicians trained in prosthodontics and 2 ex­
perts in CAD) completed digital crown designs on all
prepared teeth. The resulting designs were compared
with the STL files representing the original teeth before
preparations to assess 3D deviations. The surface devia­
tions of the digital crowns developed by both groups were
statistically compared (α=.05).
The total median 3D deviation was 0.10 mm (range:
0.03 mm to 0.61 mm) for the clinician group and 0.14 mm
(range: 0.07 mm to 0.58 mm) for the CAD group. The
clinician group developed smaller total 3D (P=.021) and
THE JOURNAL OF PROSTHETIC DENTISTRY
456
cervical margin (P=.001) deviations. There were no dif­
ferences between groups for the distal, mesial, or occlusal
surfaces (P>.05). However, the CAD group
(9.75 ±2.12 minutes) completed the digital designs faster
than the clinician group (14.69 ±4.33 minutes) (P=.001).
Within the limitations of this in vitro investigation,
the findings suggested that postgraduate training in
prosthodontics and clinical experience have a more
significant impact on the accuracy of digital contour
development for single crowns than CAD experience,
particularly related to the restoration's cervical aspects.
CAD experience permits faster digital contour develop­
ment. Finally, the authors indicated that CAD-CAM
technologies should be considered tools for enhancing
the predictability of therapies that follow the same
principles of tooth morphology and clinical prostho­
dontics used in conventional workflows.
Because of the emphasis placed on esthetics in
modern dental practice, increasing the predictability of
achieving appropriately dimensioned anterior restora­
tions is of great interest. However, while several dental
proportions have been suggested, the best restorative
anterior tooth dimensions or proportions remain un­
clear. To address this issue, Akl et al151 systematically
reviewed and compared three commonly used ratios,
including the golden proportion,152 golden percen­
tage,153 and recurring esthetic dental (RED) propor­
tion,154 to determine which if any, can be used to
provide predictable esthetic clinical outcomes.
Briefly, the golden proportion is a repeated ratio
(1:0.618) of maxillary anterior tooth widths from a
frontal view. The golden percentage uses arithmetic al­
terations of the golden proportion to bring greater
dominance to the maxillary central incisors. The pro­
posed golden percentages are 25% for the central in­
cisor, 15% for the lateral incisor, and 10% for the canine
unilaterally. The RED proportion indicates that the
widths of anterior teeth, as viewed from the front,
should remain proportionally consistent moving from
the dental midline distally.
A search of the dental literature on the subject be­
tween 1973 and 2020 returned 1031 articles. Following
critical evaluation of these articles and appraisal for
bias,155,156 54 were included in the review.
The results indicated that natural tooth proportions
vary substantially between populations, geographic lo­
cations, age groups, and sex. None of the included studies
supported a specific mathematical formula to be used as a
standardized guide for predictable esthetic success.
Within the limitations of this review, the authors
concluded that while the golden proportion may be
present between the central to lateral incisors in some
individuals, it is rarely present between the lateral in­
cisor and the canine. Although none of the proportions
investigated yield predictable esthetic success, the
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Volume 130 Issue 4
golden percentage may be a reasonable starting point if
the percentages are adjusted on a patient-by-patient
basis. Ultimately, generalized esthetic ideals do not fit
well within a mathematical formula. All are open to
clinicians’ and patients’ interpretations, preferences, and
subjectivity.
A second similar systematic review157 investigated
the quality and outcome of studies into maxillary ante­
rior tooth proportions to see if geographically specific
esthetic dental proportion ratios are appropriate. Ex­
isting evidence hints at the need for racially corrected
dental proportion ratios. If true, population-specific
dental gauges, grids, and software programs could be
developed from racially descriptive scientific data.
An electronic literature search initially identified 73
articles published from 1978 to 2020. After applying
exclusion criteria and quality assessment,158 16 full-text
articles were retained for systematic review. Each study's
general characteristics, outcomes, and quality were re­
viewed and analyzed systematically.
The geographic distribution of the selected article
revealed 12 articles from Asia, 2 from Continental
Europe, and 2 from the United Kingdom. Results dis­
agreed with the classic golden percentage theory for
maxillary anterior tooth width in pleasing smiles.
Classical golden percentage values of 25%, 15%, and
10% for the central incisor, lateral incisor, and canine
teeth were unreliable. The mean percentage widths re­
ported were 22.285 ±0.619 for the maxillary right central
incisor, 15.175 ±0.454 for the maxillary right lateral in­
cisor, 12.201 ±0.670 for the maxillary right canine,
22.285 ±0.619 for the maxillary left central incisor,
15.175 ±0.454 for the maxillary left lateral incisor, and
12.201 ±0.670 for the maxillary left canine.
The authors concluded that the classic golden per­
centage theory could not be used to develop an esthe­
tically pleasing smile design. However, its anterior
maxillary dental width ratios could be adjusted for the
race and ethnicity of the patient to produce a meaningful
aid to restorative dentistry.
Regardless of the profession’s desire to provide our
patients with high-quality, evidence-based dental
healthcare information, the reality is that most patients
visit the internet to obtain ready access to their dental
questions. Therefore, using multiple quality assessment
tools, Alshehri et al159 evaluated the readability and
quality of online patient-oriented information among
common prosthodontic search areas.
Commonly used prosthodontic keywords (veneers,
crowns, bridges, and implants) were used with two
online search engines (Google and Yahoo). The study
samples included the first 50 websites listed by each
search engine for each keyword that fell within specified
criteria. Websites targeting dentists were excluded. Each
website’s information quality was evaluated by using the
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October 2023
DISCERN questionnaire and the Health on the Net
(HON) criteria. Readability assessment was performed
using the Flesch-Kinkaid Reading Grade Level (FKRGL)
and the Flesch Reading Ease Score (FRES). The dentists
making assessments were calibrated until assessment
homogeneity was demonstrated.
Once duplicate sites had been eliminated, 225 web­
sites met the study’s inclusion criteria. Sample sites were
evenly distributed on the keywords “crowns” and
“bridges,” while “implants” was mentioned most often
and “veneers” least often. The median score for the
DISCERN instrument indicated generally poor in­
formation quality on the websites sampled. A significant
difference was found between the educational and
commercial websites in quality and readability.
Commercial websites appeared to have inferior in­
formation quality than educational websites, while
commercial and educational sites were difficult to read.
Websites containing the keyword “implants” were the
most difficult to read, followed by “veneers,” “crowns,”
and then “bridges.”
The authors concluded that internet-based health
information for routine prosthodontic therapy is gen­
erally difficult to read and of poor quality. Therefore, the
specialty of prosthodontics may be well-served to es­
tablish, optimize visibility, and promote websites that
provide reliable, high-quality, and readily accessible in­
formation about common prosthodontic interventions.
Furthermore, patient education about trusted online
resources under the supervision of qualified individuals
is essential.
Errors in location and 3-dimensional orientation of a
maxillary cast in the articulator can affect subsequent
dental restoration esthetics, the direction of the man­
dibular path of closure, and occlusal function. The Kois
Dento-Facial Analyzer (KDFA, Panadent Corp) posi­
tions maxillary casts in the articulator to evaluate and
treat patients. However, more independent information
is needed to determine if the KDFA should be con­
sidered an evidence-based alternative to conventional
means for mounting maxillary casts. To investigate this
matter, Thompson et al160 compare maxillary casts
mounted using the KDFA with casts mounted using
either an average axis facebow (PFM or Panadent Pana-
Mount Facebow; Panadent Corp) or a kinematic axis
facebow (KA or Axi-Path III Recorder; Panadent Corp).
Three maxillary irreversible hydrocolloid impressions
and resulting gypsum casts were made of 15 partici­
pants. One cast from each study participant was
mounted in an articulator (PCH; Panadent Corp) using
the KDFA, PMF, and KA. The use of these instruments
followed the manufacturer’s instructions. Standardized
photographs (frontal and lateral perspectives) of each
mounting were made. The condylar center-to-incisor
distance, occlusal plane, and incisal plane angles were
Cagna et al
457
measured. Statistical evaluation of resulting distances
and angles was accomplished.
Results indicated that the KDFA positioned the
maxillary cast at a significantly lower angle for occlusal
plane angle than PMF and KA (P<.001). For condylar
center-to-incisor distance, the KDFA and PMF cast
mountings resulted in greater distances than the KA
mountings (P=.01). No significant differences were
found for incisal plane angle resulting from maxillary
casts mounted using the KDFA, KA, or PMF
methods (P=.16).
The authors concluded that any opinion on the
clinical significance of these findings is speculative. This
study compared a relatively new system for mounting
maxillary casts to methods used for over 100 years.
Currently, a method that simultaneously records the
transverse horizontal axis and facilitates physical cast
orientation in a suitable esthetic reference position does
not exist. Digital processes may soon unravel this con­
undrum and provide an accurate and readily applicable
solution.
Conventional removable complete prosthodontics
Treating edentulism effectively, efficiently, and eco­
nomically with conventional complete dentures will
remain an essential dental procedure for the foresee­
able future. Various complete denture techniques have
been developed over the years, and several different
occlusal schemes have been recommended. While
previous studies have examined efficiency and sa­
tisfaction among occlusal scheme groups, few have
related outcomes to edentulous maxillary and man­
dibular anatomy. Grech et al161 compared patient-
reported outcomes among 3 distinct complete denture
occlusal schemes to edentulous jaw anatomic classi­
fications using a RCT design.
A total of 60 edentulous patients (mean age 68.1 ±11.1
years; age range 34 to 93 years; 34 men and 26 women)
received new complete dentures fabricated using different
occlusal schemes: balanced (simultaneous anterior and
posterior occlusal contacts in excursive movements), lin­
gualized (maxillary palatal cusp contacts with mandibular
occlusal surfaces during centric and all eccentric posi­
tions), or monoplane (posterior cuspless teeth set to a flat
plane) articulation. Demographic variables, bone ridge
quantity, number of required post-placement prosthesis
adjustments, and satisfaction (Denture Satisfaction
Questionnaire or DSQ) and quality of life (QoL) (General
Oral Health Assessment Index or GOHAI) at 1, 2, 4, 8,
12, and 52 weeks. The bone ridge quantity classification
was divided into two groups according to the Lekholm
and Zarb162 classification. Classes A, B, and C were
considered good to moderately good ridges, and classes
D and E were poor ridges.
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458
The results indicated no statistical differences in the
distribution of demographic variables (age, sex, years
edentulous, and age of existing dentures) or bone ridge
classifications among occlusal scheme groups. Similarly,
there were no statistical differences in ridge classifica­
tions, DSQ, and GOHAI values among groups for both
jaws (P>.05) over the follow-up period. However, each
group presented significant improvements in DSQ and
GOHAI scores over the course of follow-up (P<.001).
Additionally, significantly fewer denture adjustments
were required in the lingualized occlusal scheme group
compared to the other groups (P=.034).
Within the limitations of this clinical study, the au­
thors concluded that the occlusal scheme for conven­
tional complete dentures did not influence patient-
reported subjective outcomes, and no occlusal scheme
preference was observed for the different ridge classifi­
cations identified. However, fewer post-placement ad­
justments were associated with using the lingualized
occlusal scheme.
Edentulism affects oral and systemic health, and the
lack of proper food intake can adversely impact nutri­
tional status. Felix Gomez et al163 matched extensive
electronic dental record and electronic health record
(EDR-EHR) data sources to retrospectively assess the
nutritional profiles of denture wearers compared to non-
denture wearers. They assessed nutritional biomarkers
from complete blood count (CBC), comprehensive me­
tabolic profile (CMP), basic metabolic profile (BMP),
lipid and thyroid panel tests, anthropometrics (weight,
height, and body mass index or BMI), demographics,
and the presence of dental insurance. Authors indicated
that lab-value studies on nutritional biomarkers in
serum and urine samples in the EHR and linking with
EDR data had not been reported previously.
A case group (denture wearers) included matched
EDR-EHR data on patients who received conventional
removable partial, complete, and implant-supported
denture therapy between January 2010 and December
2018. A control group (non-denture wearers) group
did not receive denture therapy over the same time.
For qualified patients, EDRs were matched with EHRs
based on lab report availability within 2 years of re­
ceiving dentures. Nutritional biomarkers of interest
were complete blood count, comprehensive and basic
metabolic profile, lipid and thyroid panels. Of interest
was the rate of change over time (slope) of nutritional
biomarkers before and after receiving denture pros­
theses and the differences between dentures and
controls.
The final cohort included 10 481 individuals (55%
female) with matched EDR-EHR data, including 3519
denture wearers (mean age 57 ±10 years) and 6962
controls (mean age 56 ±10 years). Data assessment for
denture wearers indicated decreased serum albumin
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Volume 130 Issue 4
(P=.002), calcium (P=.039), and creatinine (P<.001). In
addition, hemoglobin (Hb) decreased during the ob­
servation (P<.001). In the case group, edentulous pa­
tients displayed significant decreases in serum albumin,
creatinine, and blood urea nitrogen (BUN) but increases
in estimated glomerular filtration rate (eGFR). Partially
edentulous patients revealed decreased total cholesterol
(P=.018), and TSH (P=.004) and BUN (P<.001) in­
creased. Individuals edentulous in one jaw (maxilla or
mandible) demonstrated decreased BUN and eGFR.
Denture wearers showed decreased serum albumin and
protein (P=.008) and serum calcium (P=.001) compared
with controls. Controls showed increased Hb (P=.035)
during and following the index period.
The authors concluded that nutritional biomarkers
vary among denture wearers. Using matched EDR-EHR
data can help determine denture patients' nutritional
profiles. Providing nutritional counseling from such data
analysis during denture placement may improve overall
health.
Conventional complete dentures remain a popular
treatment choice regardless of the perceived benefits of
implant-supported complete arch prostheses. In situa­
tions where complete denture retention and stability are
insufficient, denture adhesives are often recommended
to enhance prosthesis performance and patient psy­
chological well-being. To qualify the scientific basis for
such recommendations, Florêncio Costa et al164 sys­
tematically reviewed the literature to investigate the
influence of denture adhesives on conventional com­
plete denture masticatory performance.
A search of available literature on the topic initially
yielded 1338 articles, of which only 6 met the inclusion
criteria and entered the objective analysis. All included
studies were crossover RCTs and included bimaxillary
edentulous individuals. All studies evaluated masticatory
performance using a comminution and sieve method.
The Cochrane quality assessment tool149 was used to
determine the risk of bias and demonstrated a high rate
of “uncertain” assessments.
Overall findings indicated a positive effect of dental
adhesives on the masticatory performance of study
participants wearing complete dentures. However, the
authors pointed out that the limitations of this sys­
tematic review include the heterogeneity of study
methodologies and the high percentage of unclear risk
of bias. The need for more well-designed clinical trials
on this topic was suggested. From a clinical perspective,
caution was recommended in the prolonged use of
denture adhesives since systemic complications related
to the abusive use of zinc-containing materials have
been reported. Additionally, the authors indicate that
patients using adhesives should be evaluated periodi­
cally to avoid the continuous use of poorly fitting com­
plete dentures.
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October 2023
In a second similar systematic review of denture
adhesive use with conventional complete dentures in
bimaxillary edentulous patients, Lemos et al165 con­
sidered potential benefits in denture retention and sta­
bility, patient-reported outcomes measures, and
masticatory performance.
An initial search of related literature produced 3107
articles, of which 13 (12 crossover RCTs and 1 multi­
center RCT without crossover) met inclusion criteria and
entered the review. A total of 516 individuals partici­
pated in the included studies with a mean age of 65.54
years (range: 51.41 to 76.6 years). The Cochrane colla­
boration tool149 was used to analyze the risk of bias. The
grading quality of evidence and strength of re­
commendations (GRADE) tool was used to assess the
certainty of the evidence.166
Findings indicated a significant improvement in the
retention and stability, patient-reported outcomes
measures, and masticatory performance when denture
adhesive was used in conventional complete dentures
compared with no denture adhesive use. Most studies
presented a low risk of bias, but the certainty of the
evidence was classified as low to moderate. While newly
developed denture adhesives were reported to be pro­
mising, authors cautioned that additional high-quality
studies are needed to confirm these results.
Historically, the removal of conventional complete
dentures during nocturnal sleep has been recommended
to avoid soft tissue damage associated with continuous
(denture stomatitis, traumatic ulcerations, irritation hy­
perplasia, and so on). However, removing complete
dentures with concurrent mandibular closure at night
may reduce face height and upper airway volume. An
associated increase in the apnea-hypopnea index (AHI)
for individuals with OSA would be detrimental.
Sleeping without conventional complete dentures
has been reported to induce adverse effects on cardior­
espiratory functions in edentulous patients with OSA.
To clarify this issue, Uyar et al167 conducted a clinical
study assessing the impact of nocturnal complete den­
ture wear on cardiorespiratory stability as measured
using pulse oximetry (PO).
Thirty age and BMI-matched edentulous patients
were enrolled (12 women and 18 men). The first noc­
turnal pulse oximetry (FNPO) recordings were made on 3
different nights while participants slept without dentures
(WOD). Oxygen desaturation index (ODI), total re­
spiratory event (TRE), basal peripheral oxygen saturation
(B-SpO2), time ≤88% saturation (T88), average low per­
ipheral oxygen saturation (AL-SpO2), total pulse event
(TPE), average pulse rate (APR), and heart rate variability
index (HRVI), were obtained. According to the ODI
scores, participant status was qualified as normal
(ODI<5), mild (5<ODI<15), moderate (15<ODI<30), or
severe (ODI>30). Ne conventional complete dentures
Cagna et al
459
were fabricated. After 1 month of acclimation, the second
nocturnal pulse oximetry (SNPO) recordings were made
on 3 different nights while the participants wore dentures
(WD). Similar PO data were obtained. A comparison of
mean PO values obtained WOD and WD were ana­
lyzed (α=.05).
The results revealed significant differences between
WOD and WD values for TRE (P=.01), ODI (P=.001),
AL-SpO2 (P=.006), TPE (P=.001), and HRVI (P=.001)
parameters. PO parameters improved significantly for
participants who wore complete dentures nocturnally.
Specifically, the ODI scores of 22 individuals decreased
under WD condition, whereas 1 remained the same, and
increases were seen for 7 participants. The significance
of the improvements in the WD parameters increased
with the severity of OSA.
The authors concluded that significant improvements
were observed in substantial cardiorespiratory para­
meters, such as the ODI and HRVI, for participants
wearing nocturnal dentures. Additionally, until well-
designed studies with more participants are published
and a consensus is reached: clinicians can use PO to
establish a regimen for the nocturnal usage of dentures.
The authors cautioned that continuous complete den­
ture wear is not recommended. It is important to remind
patients that wear their complete dentures at night to
remove them during the day for prescribed periods.
Conventional removable partial prosthodontics
Changes in edentulous ridge morphology due to re­
sorptive processes are likely with continued wear of
removable partial denture (RPD) despite appropriate
personal and professional management. The popular
theory relates functional loading forces on the prosthesis
to ridge changes over time, necessitating denture base
reline. Unfortunately, accurate assessment of expected
functional loading can be challenging. One diagnostic
feature that may be useful in predicting occlusal loading
forces is the gonial angle (GAO) measured on lateral
cephalograms. While cephalograms are infrequently
used in most practices, panoramic radiographs are more
common and present similar gonial angular geometry.
Wada et al168 reported investigating the association
between GAO and reline frequency in RPD wearers.
A total of 65 patients (32 men, 33 women; median
age: 66.5 years; age range: 61.3 to 71.8) who recently
received distal extension base RPDs (26 maxillary, 39
mandibular) were enrolled in the study. Age, sex, number
of remaining teeth, remaining opposing teeth, and sup­
porting RPD abutments were recorded. The GAOs on
panoramic radiographs were defined as the angle formed
by the inferior and posterior borders of the mandible.
The necessity for denture base relining was determined
by guidelines set forth by the Japan Prosthodontic
THE JOURNAL OF PROSTHETIC DENTISTRY
460
Society. Calculating the time interval between reline
events (mean number of days between denture insertion
and the first or subsequent relines) indicated the rapidity
of ridge resorption.
The results indicated that the median relining in­
terval was 533.3 days, and the median GAO was 123
degrees. A significant positive correlation existed be­
tween the mean relining interval and GAO (rs=.335;
P=.006). The number of remaining opposing teeth (rs=-
0.187; P=.137) and RPD abutment supports (rs=-0.214;
P=.087) exhibited weak negative correlations with mean
relining interval. Multivariate analysis showed that GAO
was a significant explanatory variable for the mean re­
lining interval.
The authors concluded that the need to reline distal
extension base RPDs might occur quicker after pros­
thesis placement and more often in patients with rela­
tively small GAOs. Therefore, practitioners should
assess GAOs on panoramic radiographs and consider
that the relationship between GAO and potential oc­
clusal force generation may affect reline frequency when
distal extension base RPDs are worn.
The CAD-CAM opportunities for RPD framework
fabrication are relatively new to the digital dentistry
landscape. Possible advantages on the CAD side include
improved planning with geometric analysis tools, auto­
mated determination of paths of placement and re­
moval, practical assessment and control of abutment
undercut areas, and ease of design archiving for future
retrieval and framework re-manufacturing when ne­
cessary. On the CAM side, additive and subtractive
fabrication options incorporating various materials are
possible. However, consensus on indications and clinical
performance of digitally designed and manufactured
RPD frameworks is lacking. To address this shortfall,
Pordeus et al169 developed a systematic review and
meta-analysis evaluating CAD-CAM RPD framework
manufacturing and clinical performance.
The authors completed a comprehensive search of
the literature extending to September 2019. Their PICO
question was, "Do CAD-CAM frameworks perform si­
milarly to those fabricated using conventional techni­
ques?" The meta-analysis included clinical and in vitro
studies that measured internal fit discrepancy of the
CAD-CAM frameworks evaluated using the Effect Size
and Test of Null (2-Tail: Z-value and P-value) with a
95% confidence interval. Clinical and in vitro studies
were selected and analyzed separately.
The initial search identified 358 publications, of
which only 15 articles (7 in vitro studies, 2 clinical stu­
dies, and 6 clinical reports) entered the review. For the
clinical studies, quantitative analysis on a sample of 25
participants indicated a mean occlusal rest fit dis­
crepancy of 184.91 µm (95% CI: 152.6 µm to 217.15 µm)
and heterogeneity (I2) of 0%. Clinical data considered
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that frameworks were acceptable for the continuity of
treatment.
The dominant materials used were cobalt chromium
(Co-Cr) and polyetheretherketone (PEEK). Studies in­
vestigating Co-Cr reported that the frameworks required
adjustments. In addition, the indirect technique (stereo­
lithographic resin pattern + conventional metal casting)
was time-consuming, and selective laser melting (SLM)
can be costly. PEEK structures have been more widely
accepted because of improved esthetics. Quantitative data
(mean fit accuracy of rests) from the in vitro studies re­
vealed that the additive manufacturing technique
(2.006 mm; 95% CI: -2.021 to 6.032 mm; P=.329) was not
significantly different from the indirect technique
(0.026 mm; 95% CI: -0.042 to 0.093 mm; P=.455).
However, significant heterogeneity was observed be­
tween analyses (I2=98.402, random-effects model).
The authors indicated that clinical studies and in
vitro research on CAD-CAM RPD frameworks are still
sparse. However, preliminary findings indicate a similar
fit between digital and conventional methods, while
PEEK offers some esthetic advantages because of the
color of the framework. Although beyond this report,
the authors suggested that the software program used
and the level of experience of the operator may influence
RPD quality. Overall, using CAD-CAM technology for
manufacturing RPD frameworks is a suitable option.
To delve further into the digital manufacturing of
RPD frameworks, Peng et al170 reported on an in vitro
investigation looking at the trueness of SLM-fabricated
RPD frameworks made from Co-Cr and titanium-alu­
minum-vanadium (Ti-6Al-4V) alloys, compared with
frameworks fabricated using the traditional lost-wax
casting process.
A digital scan of a Kennedy class II (modification 2)
mandible model, prepared to receive an RPD, was
made. An RPD framework was digitally designed, and
the virtual RPD framework was exported as an STL file
labeled CRF (CAD reference framework). Two groups
of frameworks were fabricated using SLM from the
CRF, a Co-Cr (SLM-Co-Cr, n=6) group and a Ti-6Al-
4V (SLM-Ti-6Al-4V, n=6). A control group of frame­
works was made using stereolithography resin pat­
terns subjected to traditional lost-wax casting (CA-Co-
Cr, n=6). At completion, 18 RPD frameworks were
digitally scanned and labeled CEF (CAD experimental
frameworks). Each CEF was then superimposed on the
CRF and evaluated for discrepancies using a 3D ana­
lysis software program to determine differences in
trueness among groups (α=.05).
The results indicated that the control (CA-Co-Cr)
group displayed the greatest discrepancy compared to the
reference (CRF) scans. Significant differences were found
between the control and SLM-fabricated groups (P=.03
for SLM-Co-Cr, and P=.016 for SLM-Ti-6Al-4V). No
Cagna et al
October 2023
significant difference was found between the SLM-Co-Cr
and SLM-Ti-6Al-4V experimental groups (P=.787).
The authors concluded that SLM-fabricated RPD
frameworks with either alloy exhibited greater trueness
than traditionally fabricated frameworks. However, also
noted was the need to detect the gap distance between
the master model and the RPD frameworks’ fitting
surfaces. The present study only considered overall
discrepancies between framework scans. Further studies
in this area are warranted.
Using chemical soaking solutions to help disinfect
RPDs may supplement the mechanical removal of debris
and biofilm. Unfortunately, while some soaking solu­
tions are effectively antibacterial, they also pose dis­
advantages, including alteration of acrylic resin color,
metal alloy corrosion, oral cytotoxicity, unpleasant taste,
and skin irritation. Recently, a vinegar-hydrogen per­
oxide mixture was reported to be effective in eliminating
Candida albicans and Staphylococcus aureus from denture
base acrylic resin, with an action comparable to sodium
hypochlorite or peracetic acid.171 However, the effects of
this mixture on the Co-Cr alloy of RPD frameworks
remain unknown. To evaluate potentially detrimental
effects, Feldmann et al172 investigated the surface
roughness, Knoop microhardness, surface free energy,
and wettability of a Co-Cr alloy when exposed to a vi­
negar-hydrogen peroxide mixture.
Fifty cast Co-Cr alloy specimens were immersed for
900 minutes (simulating 3 months of 10 min/day im­
mersion) in the following fluids (n=10 each): distilled
water, 0.5% sodium hypochlorite, 3% hydrogen peroxide
+water dilution (1:1 ratio), white-wine vinegar+water
dilution (1:1 ratio), and vinegar+hydrogen peroxide
mixture (1:1 ratio). Physical properties were measured
with single blinding before and after immersions, and
subsequent data were statistically analyzed (α=.05).
Results indicated that the vinegar+hydrogen per­
oxide mixture did not affect the surface roughness or
Knoop microhardness of the Co-Cr alloy specimens.
However, 0.5% sodium hypochlorite significantly in­
creased surface roughness (P=.004) and decreased mi­
crohardness (P=.048). In addition, surface free energy
and wettability increased after immersions, regardless of
solution type (P<.001).
Based on these findings, the authors concluded that
the vinegar-hydrogen peroxide mixture investigated did
not adversely affect the surface properties of the RPD
framework Co-Cr alloy, while the 0.5% sodium hypo­
chlorite negatively affected surface roughness and
Knoop microhardness. Therefore, as a soaking solution
for RPD disinfection, the vinegar-hydrogen peroxide
mixture shows promise because it is as effective in
eliminating C. albicans and S. aureus as sodium hypo­
chlorite171 and does not have deleterious effects on
metal surfaces as demonstrated here.
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461
Conventional fixed prosthodontics
While the popularity of monolithic zirconia restorations
has increased substantially over the past decade, long-
term evidence supporting this restoration's clinical per­
formance and durability remains scarce. Still needed are
clinical studies with follow-up data longer than 5 years,
clinical randomized trials, and success rate indications
over the medium and long term. To address these issues,
Leitão et al173 conducted a systematic review and meta-
analysis to evaluate the survival rate, biological compli­
cations, technical complications, and clinical behavior of
single monolithic zirconia crowns supported by teeth
and manufactured using CAD-CAM technology.
A focused research question was defined through the
population, intervention, comparison, outcomes, and
time (PICOT) format,174,175 “In an adult population, do
monolithic zirconia restorations on natural teeth de­
monstrate superior survival and clinical performance
during a minimum 3-month follow-up?” Extensive
electronic and manual literature searching initially
identified 1074 articles, of which 9 entered the sys­
tematic review. Published between 2014 and 2019, these
articles included 1 RCT, 3 prospective cohort clinical
trials, 1 prospective observational case series, 2 retro­
spective clinical trials, 1 retrospective observational
clinical trial, and 1 retrospective observational case series
(55.6% prospective; 44.4% retrospective).
This review included 594 participants (average age:
49.1 years; 238 men, 316 women) and 1657 single-tooth
restorations (22.2% anterior, 88.9% posterior) with a
mean exposure time of 1.07 years and a follow-up period
between 0.3 and 2.1 years. All studies showed a moderate
level of quality with associated moderate risk of bias
(Newcastle-Ottawa Scale or NOS) and 91-100% survival
rates (SR). Bleeding on probing (BOP) averaged 29.12%.
Marginal integrity was highly successful for the ob­
servation periods, except for 1 study that reported bruxers
with a 31.60% SR. Failures and fractures were observed in
3 studies. No statistical correlation existed between the
survival rate and the type of cementation (P=.730) or the
average years of follow-up (P=.454). There was high
heterogeneity (Cochran Q Test) between studies for SR
(I2=92.49%; Q=81.518) and the relationship between SR
and BOP (I2=93.74%; Q=79.672).
Limitations of this systematic review related to poor
methodology standardization, a reduced number of
studies and controlled protocols, high heterogeneity,
limited clinical follow-up periods, and a limited number
of acceptable studies reporting SRs for monolithic zir­
conia restorations. Nevertheless, the authors concluded
that monolithic zirconia might be considered a reason­
able single-restoration option, particularly for posterior
teeth. Additional clinical research is needed and should
include RCTs. These clinical trials must involve large
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462
patient samples and long follow-up periods to docu­
ment clinical effects reliably.
Fixed prosthodontic treatment is clinically challen­
ging and may harm the pulp and periodontal tissues.
Thermal injury, chemical insult, and pre-existing tooth
conditions can eventually affect abutment tooth vitality.
Evidence related to the failure of fixed prosthodontic
restorations solely based on endodontic deterioration is
currently inadequate. Kohli et al176 completed a sys­
tematic review to identify the incidence of pulp necrosis
and periapical changes among vital teeth serving as
abutments for single crowns and fixed partial den­
tures (FPDs).
The PICO question developed was, “What is the
success rate of prosthesis based on the maintenance of
pulpal vitality of abutment teeth, compared to failure
due to incidence of pulpal necrosis or periapical changes
in patients receiving crown or FPD treatment on vital
abutment teeth?” An electronic and manual search of
the literature through 2021 was accomplished. The
search targeted clinical and radiographic crown or FPD
failures involving vital permanent teeth over a minimum
of 12 months of follow-up. Study quality was assessed
using the Newcastle-Ottawa Quality Assessment Scale
(NOS) for cohort studies. The meta-analysis involved a
random effects model, and publication bias was assessed
using funnel plots.
The initial search yielded 5835 articles, eventually
producing 20 studies for the SR systematic review and 7
studies for the meta-analysis. All included studies were
high quality (NOS scores between 6 and 9).
The meta-analysis included a total of 2247 patients.
Nine studies examined FPDs, 4 studies involved crowns
only, and 7 studies followed both crowns and FPDs. A
total of 2290 FPDs, 3368 single crowns, and approxi­
mately 6667 vital teeth were evaluated. Most studies
included both men and women. The clinical follow-up
times ranged from 2 to 25 years.
The meta-analyses showed no significant differences
in the incidence of pulp vitality loss or pulp necrosis
through clinical and radiographic examination with
follow-up periods of 5 years (P<.001; 95% CI: 0.96-1.00;
I2=77.84%), 10 years (P<.001; 95% CI: 0.88-0.95;
I2=93.59%), 15 years (P<.001; 95% CI: 0.92-0.96;
I2=94.83%), and 20 years (P<.001; 95% CI: 0.94-0.96;
I2=95.01%). Moderate to substantial heterogeneity be­
tween studies was noted at all time points. Since a
minimum number of studies are required to assess
publication bias, this was only possible at the 10-year
follow-up period. Here, publication bias was observed.
More studies with large sample sizes are required to
verify these results.
The authors concluded that favorable clinical and
radiographic success rates (92 to 98%) could be expected
for follow-up periods between 5 and 20 years. This
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Volume 130 Issue 4
explains the low incidence of pulpal necrosis or peria­
pical lesions involving these initially vital and healthy
fixed prosthodontic abutments. However, future high-
quality RCTs involving larger patient populations are
required for confirmation since only observational stu­
dies were considered in this report.
As the desires of both patients and practitioners for
metal-free fixed prosthodontic solutions increase, ex­
tensive, high-quality, long-duration clinical research
must establish a firm scientific foundation for the pro­
fession to stand on. Matta et al177 conducted a pro­
spective clinical trial to evaluate three- and four-unit
posterior zirconia FPDs veneered with feldspathic por­
celain after 10 years of clinical use.
The present study is a continuation of previously
published data for ceramic FDPs evaluated after 3
years178 and 5 years179 of clinical service. Here, clinical
evaluation (restoration condition and stability) of 15
FPDs (7 maxilla; 8 mandible) after 10 years of function is
reported. The FPDs were fabricated using feldspathic
ceramic-veneered, 3-yttria-stabilized, tetragonal zirco­
nium dioxide frameworks. Restorations replaced one or
two missing teeth with spans ranging from 12 to 19 mm.
The data collection was based on modified California
Dental Association (CDA) criteria and included, for ex­
ample, the anatomic form, shade, surface texture, mar­
ginal integrity, proximal contacts, occlusion, finish line
placement, endodontic status, caries status, plaque ac­
cumulation, BOP, pocket depths, functionality, esthetics,
and complications. In addition, restoration success and
survival rates were calculated.
Results revealed that these ceramic FPDs demon­
strated excellent biocompatibility and color reproduc­
tion. The success rate of the FDPs evaluated was
determined by the success of the veneering ceramic, and
ceramic chipping was considered a failure of the re­
storations. Since chipping was detected in 40% of the
prostheses, accounting for the largest share of all ob­
served complications, the restoration success rate was
60%. The survival rate was 88.2%, as 2 of the restora­
tions were lost.
The authors concluded that this ceramic concept for
posterior FDPs achieved satisfactory results after 10
years. The main problem was chipping, a generally re­
cognized concern with this material combination over
time. Otherwise, the FPDs were characterized by ex­
cellent esthetics and biocompatibility. Monolithic zir­
conia is another ceramic option which circumvents the
risk of chipping. However, long-term clinical studies are
increasingly needed for this monolithic alternative to
make conclusive statements regarding this application's
durability and clinical utility.
To appropriately manage excessive tooth wear, con­
sideration must be given to the complex etiology of the
problem, as well as several challenging materials and
Cagna et al
October 2023
mechanical aspects of potential restorative approaches.
Unfortunately, evidence on this clinical issue is sparse,
and recommendations are generally limited to clinical
experience and authoritative opinions. To facilitate the
needed evidence basis, Hammoudi et al180 conducted a
RCT comparing the clinical performance, longevity, and
success rate of crowns made of different popular ceramic
materials, pressed lithium disilicate (LD, IPS e.max-
Press; Ivoclar AG) and translucent zirconia (TZ, BruxZir
Solid Zirconia, 3Y-TZP; Glidewell Laboratories), for the
restoration of extensively worn dentitions.
Sixty-two participants with extensive tooth wear (17
women, 45 men; mean age 44.8 years; range 25-63
years) entered a single-center, double-blind, RCT con­
ducted from 2012 to 2018. Most of the participants
sought treatment for esthetic reasons (83.9%), pro­
gressive tooth wear (59.7%), tooth hypersensitivity
(38.7%), and masticatory problems (24.2%). Individuals
were placed into 2 relatively well-defined, albeit over­
lapping, chemical and mechanical clusters based on
perceived primary wear etiologies. Participants were
then randomized into experimental groups (32 in LD
group; 30 in TZ group) and received 713 crowns (362 LD
crowns; 351 TZ crowns; 342 anterior; 371 posterior).
Crowns were luted to preparations with chamfer finish
lines using 10-methacryloyloxydecyl dihydrogen phos­
phate-based self-etching adhesive cement (Panavia
F2.0; Kuraray Noritake Dental Inc). The restorations
were clinically evaluated on average 14, 31, 39, 54, and
65 months after placement according to modified United
States Public Health Service (USPHS) criteria.
After observation of up to 6 years, the survival rate
for both crown types was 99.7%. One LD crown was lost
after 1 year (loss of retention), and 1 TZ crown was lost
after 3 years (tooth fracture). The success rates were
similar (LD=98.6%; TZ=99.1%). Reasons for failures
included apical lesion development, ceramic fractures, or
crown re-cementation. Color assessment at baseline was
significantly different, with a better match for LD (84.8%
Alfa, 15.2% Bravo) than for TZ crowns (36.5% Alfa,
63.5% Bravo), including TZ crowns with veneered por­
celain (P<.001). Secondary caries and cracks were not
observed. A post hoc clinical performance analysis in­
dicated no significant differences for patients with pri­
marily mechanical or chemical etiologies for extensive
tooth wear.
The authors concluded that they observed no dif­
ferences between the ceramic crowns investigated
related to long-term success or clinical performance,
except that LD crowns were rated as more esthetic.
Both LD and TZ crowns used to restore extensive
tooth wear showed promising survival rates of 99.7%
over 6 years of follow-up. The authors also com­
mented that bulk fracture did not occur, despite sev­
eral thin restorations (0.6 mm to 1.0 mm). For patients
Cagna et al
463
with extensive tooth wear, resin-bonded, less in­
vasive, high-strength ceramic crowns may be bene­
ficial. Key to differential material selection for this
challenging patient population may be the improved
esthetic appearance of LD.
General implant prosthodontics
When natural teeth are lost, the associated mechan­
oreceptors in the periodontal ligaments (PDLs) no
longer participate in modulating oral motor functions
such as mastication and speech. Following dental im­
plant placement, low peri-implant nerve fiber density
and the lack of PDL receptors make it difficult for pa­
tients to perceive mastication forces and passive occlusal
loading. The absence of sensory-mitigated implant
overload can have adverse biological and mechanical
consequences.
The phenomenon of osseoperception (the ability to
perceive tactile sensation via mechanoreception in the
peri-implant environment) has been suggested. To in­
vestigate this phenomenon, Song et al181 systematically
reviewed available literature. Their PICO question was,
“Can neurosensory innervation be restored following
dental implant treatment, and what factors may affect its
restoration?”.
A literature search extending to June 2021 initially
yielded 1667 articles. The application of exclusion
criteria rendered 22 publications eligible to enter the
review. Both human and animal studies were con­
sidered. The quality of experimental methods was
assessed using the Cochrane risk of bias tool for
human studies149 and the SYRCLE risk of bias tool for
animal studies.182 All reports were non-randomized
and retrospective in design (low level of evidence),
focusing on post-treatment oral sensory function or
peri-implant innervation. Fourteen articles used psy­
chophysical assessment (active or passive tactile
function), 5 articles performed histology (nerve fibers
in peri-implant tissues), and 3 articles evaluated
neurophysiology (cortical plasticity).
The psychophysical evidence demonstrated the re­
duced tactile function of implants. Interocclusal sensi­
bility thresholds were 5 (active threshold) and 50
(passive threshold) times higher for implants than nat­
ural teeth, although implant restorations were more
sensitive than conventional prostheses. Patient age, sex,
time of implantation, implant properties, and prosthesis
time in function did not influence the outcome.
Neurophysiology revealed evidence of cortical plasticity
following dental implant placement. The histological
evidence demonstrated myelinated nerve fibers in the
peri-implant tissues, with immediate implant placement
and loading showing significant effects on peri-implant
re-innervation.
THE JOURNAL OF PROSTHETIC DENTISTRY
464
The authors concluded that evidence exists to sup­
port an osseoperception phenomenon for restoring a
sensory feedback pathway following dental implant re­
habilitation. The authors suggested that the presence of
adjacent natural teeth appears to assist the recovery of
sensory function, with immediate implant placement
and loading protocols facilitating the presence of neu­
rosensory fiber in peri-implant tissues. Periosteal re­
ceptors may compensate for the loss of PDL
mechanoreceptors following tooth extraction and im­
plant placement. Post-implant placement cortical plas­
ticity might reinforce the osseoperception phenomenon.
Further studies are needed.
Peri-implantitis is significantly associated with dental
implant failure. A primary etiologic factor and the target
of preventive and corrective therapy is biofilm formation
on dental implant components. Compared with titanium
components, the reduced tendency for biofilm accumu­
lation has been a suggested advantage of zirconia (Zir)
implant components. To consider available evidence on
the influence of implant abutment material on biofilm
formation in the oral environment, Del Rey et al183 re­
ported on a systematic review of the literature. The fo­
cused PICO question was, “Is the oral biofilm formed on
ceramic, metal, or polymer abutment materials different
from the biofilm formed on titanium (Ti) or Ti-alloy
abutment surfaces in clinical or in situ conditions?”.
A thorough literature search, extending to 2020, and
the application of rigorous exclusion criteria resulted in
the identification of 10 clinical (8 quasi-RCTs, 1 RCT, 1
prospective cohort) and 9 in situ studies (7 within-sub­
ject design, 2 crossover design) that were included in
this review. Primary outcomes consisted of microbial
counts/profile, cell viability, and biofilm coverage/thick­
ness, while clinical parameters were considered sec­
ondary outcomes. Meta-analysis was not performed due
to heterogeneity across studies involving study designs,
experimental methods, and outcome metrics.
The risk of bias was assessed by Rob 2184 and RO­
BINS-I185 tools. For RCTs and crossover trials, 2 reports
were judged to raise some concern, and 1 was at low risk
of bias. For non-randomized clinical and in situ reports,
all studies were considered at moderate risk of bias.
A total of 972 abutments were reported, covering the
following abutment materials: 461 Ti or Ti-alloy, 392 Zir,
40 alumina, 40 gold-platinum alloy, 16 cobalt chromium
alloy, 15 polytetrafluoroethylene (PTFE), and 8 gold
alloy. Six of the 10 clinical studies (60%) and 4 of the 9 in
situ studies (44%) found no qualitative or quantitative
microbiologic differences between tested materials.
When significant differences were detected, conflicting
results were reported. However, clinical outcomes were
consistent with healthy conditions for all investigated
materials.
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Volume 130 Issue 4
The authors concluded that evidence is insufficient to
support a relevant microbiologic difference in the biofilm
formed under oral conditions on alternative abutment
materials compared to standard Ti and Ti-alloy surfaces.
It was noted that in situ studies and polymicrobial
analyses tended to demonstrate significant differences
between materials. The authors suggested that a mi­
crobiologic basis for implant abutment material selection
should only be used once reliable evidence becomes
available.
While the use of implant-assisted prostheses in the
restoration of edentulous mandibles is generally con­
sidered an improvement compared to conventional
complete dentures, a consensus based on patient pre­
ferences for overdentures or fixed prostheses is limited.
The intent of a systematic review and meta-analysis
reported by Borges et al186 was to compare the patient-
reported outcome measures or PROMs (QoL and sa­
tisfaction) and clinical outcomes (survival rate, probing
depth or PD, and marginal bone loss or MBL) associated
with implant-supported overdentures and implant-
supported fixed prostheses in edentulous mandibles.
A literature search for RCTs and non-randomized
clinical trials (N-RCTs) extended to September 2020.
After applying exclusion criteria and full-text assess­
ment, 10 studies (5 RCTs, 5 NRCTs) entered the quali­
tative and quantitative synthesis. The risk of bias was
assessed by the revised Cochrane risk of bias tool for
RCTs (RoB 2184) and N-RCT (ROBINS-I185). Quality
assessment of included RCTs revealed a high risk of bias
in 4 of the 5 studies. Assessment of NRCTs revealed a
high risk of bias in 3 of the 5 reports and a moderate risk
of bias in the remaining 2 studies. Data sets for oral
health-related quality of life (OHRQoL), satisfaction,
survival rate, implant PD, and MBL were measured and
assessed.
Results indicated that fixed prostheses showed sig­
nificantly higher QoL when compared with over­
dentures for 3 of the 6 domains of OHRQoL, including
functional limitation (P<.001), physical disability
(P=.001), and physical pain (P=.003). In addition, the
prostheses were associated with similar QoL for han­
dicap (P=.13), psychological disability (P=.31), and social
disability (P=.82).
When compared with overdentures, fixed prostheses
were associated with improved satisfaction in comfort
(P=.02), ease of mastication (P<.001), retention (P<.001),
and stability (P<.001) domains. Only ease of cleaning
presented greater satisfaction for the overdenture group
(P<.001), and ease of speaking (P=.29) and esthetics
(P=.38) were similar between groups. In addition, pa­
tients preferred fixed implant-supported prostheses for
the overall OHRQoL score (P=.01) and the overall sa­
tisfaction score (P=.01).
Cagna et al
October 2023
Clinical parameters did not differ statistically (P>.05)
between prosthesis types. For overdentures, the number
of implants that survived was 416 out of 427; for fixed
prostheses, the number was 299 out of 402.
The authors concluded that the patient-reported
outcomes measures for OHRQoL and satisfaction de­
monstrated a tendency for patients to prefer fixed im­
plant-supported prostheses to implant overdentures.
However, clinical assessment based on implant survival
rate, MBL, and PD indicated that overdentures are no
less efficient than fixed prostheses.
Several implant impression studies were published in
2022 that are worth consideration. The first is an over­
view of available systematic reviews and meta-analyses
(SRMAs). Gaikwad and coauthors187 argued that avail­
able evidence presents conflicting data that risks mis­
leading clinicians. Therefore, their objective was to
summarize SRMAs and determine the evidence-based
effectiveness of impression techniques. Their focused
research question was, “What is the difference in accu­
racy, clinical time efficiency, and patient preference
among different impression techniques for implant-
supported prostheses in edentulous and partially eden­
tulous patients.”
A comprehensive literature search extending to
April 2021 initially yielded 328 SRMAs. After applying
exclusion criteria and full-text analysis, 28 articles
involving 42 clinical trials and 203 laboratory studies
remained for systematic assessment. Most of these
articles were published between 2016 and 2021; none
were Cochrane systematic reviews. Meta-analyses
were performed in 8, and a network meta-analysis in 1
of the included reviews. In 17 of the SRMAs, the as­
sessment of the risk of bias in the primary reports was
not accomplished. The methodologic quality of the
SRMAs included here was determined using the R-
AMSTAR tool, and the degree of overlap of primary
studies was assessed.188
Results indicated that digital implant impression
techniques (DIITs) were compared with conventional
implant impression techniques (CIITs) in 22 reviews,
different DIITs were compared in 3 reviews, and dif­
ferent CIITs were compared in 9 reviews. Overall, the
methodologic quality was moderate (mean: 26.7 ±5.5)
with a slight overlap of primary studies (CCA; 5.23%).
The authors’ conclusions based on the findings were
as follows: (1) DIITs are more accurate than CIITs in
partially edentulous arches with ≤3 implants; (2) mul­
tiple implant edentulous DIITs are not accurate, (3)
DIITs are more time efficient and preferred by patients;
(4) similar accuracy was achieved with direct and in­
direct CIITs in partially edentulous arches with ≤3 im­
plants; (5) direct splinted CIITs are more accurate in
edentulous arches with multiple implants than non­
splinted techniques; and (6) cautious interpretation of
Cagna et al
465
these results is required due to moderate methodologic
quality and slight overlap of primary studies.
The authors suggested the need for studies that
follow strict guidelines and robust methodologies to
substantiate these findings and provide strong evidence
to direct clinical procedures. In addition, new clinical
instruments to measure implant impression accuracy are
needed.
Not included in the Gaikwad et al report was an in
vitro investigation reported by Lyn et al189 that com­
pared the trueness of implant scans acquired using an
intraoral scanner (IOS) with a conventional splinted
open-tray impression technique and to determine the
influence of different evaluation methods (best-fit al­
gorithm with absolute linear deviation) on accuracy as­
sessment.
A mandibular edentulous acrylic resin master model
included 8 implants evenly distributed around the arch.
Open-format STL data sets (1 laboratory scanner re­
ference file, 10 IOS files, and 10 digitized conventional
impression files) were imported to a metrology software
program. Five groups of scanning ranges were used to
simulate different clinical situations (2 unilateral pos­
terior implants, 3 unilateral posterior implants, 4 anterior
implants, 6 anterior implants, and 8 evenly distributed
implants). Two evaluation methods (the best-fit algo­
rithm and the absolute linear deviation) were used to
describe the trueness values. In addition, the impact of
different scanning/impression methods, scanning
ranges, and evaluation methods were assessed.
The results indicated that the trueness of the implant
impressions was significantly affected by different
scanning or impression methods (P<.001), evaluation
methods (P<.001), and scanning ranges (P<.001). Using
the best-fit algorithm, digital scans resulted in sig­
nificantly greater deviations than conventional im­
pressions for cross-arch implant distributions (4 anterior
implants, 6 anterior implants, and 8 evenly distributed
implants). Using the absolute linear deviation method,
significantly reduced accuracy was seen with larger im­
plant distributions (6 anterior implants and 8 evenly
distributed implants). Using the absolute linear devia­
tion method resulted in higher inaccuracy scores when
compared with the best-fit algorithm in most situations.
The authors concluded that scanning or impression
methods, scanning ranges, and evaluation methods af­
fected the trueness of scans/impressions involving mul­
tiple implants. Digital scans were less true than
conventional splinted open-tray impressions for expanded
cross-arch implant distributions. The authors caution that
precision, the other important parameter of accuracy be­
sides trueness, was not evaluated in this study.
Finally, Alpkılıç et al190 compared the trueness and
precision of 4 IOSs and conventional splinted open-tray
implant impressions (SOCI) using an in vitro protocol
THE JOURNAL OF PROSTHETIC DENTISTRY
466
with mandibular models replicating 4 different clinical
scenarios: missing right-side posterior teeth with 3 im­
plants evenly distributed in the space (Model A); missing
anterior teeth with 3 implants evenly distributed in the
space (Model B); missing right-side posterior and all
anterior teeth with 5 implants evenly distributed in the
space (Model C); and edentulous arch with 7 implants
evenly distributed between second molar sites (Model
D). Each experimental model was scanned with a high-
resolution desktop scanner (Solutionix C500, MEDIT)
and the aid of PEEK scan bodies. The resulting STL files
were archived for reference.
Each model was scanned 10 times using 4 different
IOSs (Aadva IOS, GC; CS 3600, Carestream; TRIOS 3,
3Shape A/S; and Emerald, Planmeca). As recommended
in recent literature, a single scan path was used for all
scans. The splinted open-tray polyvinyl siloxane (PVS)
technique was used for conventional impressions.
Impressions were cast in gypsum and subsequently di­
gitized for comparison. Trueness and precision were
evaluated using the digital superimposition of scanned
data (Geomajic Studio 2012; Geomajic) and statistical
assessment (α=.05).
The results indicated that the truest impressions of
Models A and B were made using the Aadva IOS, fol­
lowed by the CS 3600 IOS, the PVS conventional
technique, the TRIOS 3 IOS, and the Emerald IOS. For
Model C, the truest impressions were made with the CS
3600 IOS, followed by the Aadva IOS, PVS conventional
technique, TRIOS 3 IOS, and Emerald IOS. For eden­
tulous Model D, the truest impressions were made using
the Aadva IOS, followed by the CS 3600 IOS, PVS
conventional technique, Emerald IOS, and TRIOS 3 IOS
(P<.05). There were no significant differences in preci­
sion between groups for Models A, B, and C (P>.05).
However, the PVS conventional impression technique
showed lower precision values than other groups in
Model D (P<.05).
Given the limitation of this in vitro protocol, the
authors concluded that, for the partially edentulous
scenarios investigated, IOSs are as true and precise as
the conventional PVS technique, except for the poorly
performing Emerald IOS. However, the trueness of IOSs
was unfavorable in the edentulous scenario investigated.
Therefore, the authors suggested that a digital scanning
technique using IOSs for complete arch edentulous
implant recording cannot be recommended at present.
Implant removable prosthodontics
Routine implant overdenture hygiene practice includes
brushing the prosthesis to facilitate debris removal.
Although generally not recommended, many patients
incorporate toothpaste while brushing their over­
dentures. Daily brushing is likely to result in wear of the
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Volume 130 Issue 4
incorporated attachment inserts, which may be ex­
acerbated by including toothpaste in the process.
Unfortunately, the effect of brushing on overdenture
attachment retention is lacking. Kamonkhantikul et al191
reported on an in vitro study evaluating the retentive
force of inserts from different overdenture attachment
systems after brushing with different media.
Three abutments and 20 metal housings from each of
3 overdenture attachment systems (LOCATOR,
LOCATOR R-Tx; Zest and Novaloc; Institut Straumann
AG) were separately embedded into individual acrylic
resin testing blocks. Twenty retentive inserts from each
attachment system were individually placed into the
metal housings. The testing blocks were divided (10 per
group) depending on the brushing media. The blocks
were fixed in a brushing machine, and inserts were
brushed with deionized water (DI) or toothpaste slurry
(TP). After 0 (baseline), 10 000, and 20 000 brushing
cycles, the blocks were mounted in a universal testing
machine. The retentive force was evaluated by pulling
the blocks apart until complete abutment-insert se­
paration was achieved. The maximum retentive force
was measured 5 times and averaged. Then, the retentive
inserts were removed, replaced, and subjected to the
next test cycle. Representative specimens from each
group were examined with scanning electron micro­
scopy (SEM). The retentive force recordings were sta­
tistically analyzed (α=.05).
Results revealed that the retentive force of the
LOCATOR and LOCATOR R-Tx inserts demonstrated
different interactions between brushing media and
brushing cycles (P<.05). At 20 000 brushing cycles with
DI, the LOCATOR and LOCATOR R-Tx groups showed
reduced retention (P<.05). At 20 000 brushing cycles
with TP, the retentive force of the LOCATOR group
increased (P<.05), while the that of the LOCATOR R-Tx
remained unchanged (P>.05). Concerning brushing
media, LOCATOR retention was greater after brushing
with TP compared with DI (P<.05), and LOCATOR R-Tx
retention was similar after use of both media. In addi­
tion, SEM images revealed abrasive wear and fraying of
the nylon LOCATOR and LOCATOR R-Tx inserts after
brushing.
The retentive force of Novaloc inserts demonstrated
significant differences only for brushing cycles (P<.05),
not brushing media (P>.05). The Novaloc group showed
a decrease in retention over time. SEM images of the
PEEK Novaloc inserts demonstrated no wear or defor­
mity after brushing.
Information regarding the effect of brushing media,
deionized water, and toothpaste slurry on the retentive
force of retentive inserts is scarce. While statistically sig­
nificant differences in the retentive strength of most re­
tentive inserts were found after 20 000 brushing cycles,
the differences in retentive force before and after brushing
Cagna et al
October 2023
might not be clinically relevant compared with other
factors, including insertion and removal cycles, inter-
implant angulation, implant positioning, number of im­
plants, and functional loading levels. However, the data
produced may help clinicians select an appropriate im­
plant overdenture attachment system considering re­
tentive insert durability and patient hygiene instructions.
Despite the ongoing popularity of implant over­
dentures and studies addressing attachment systems and
implant loading protocols, the systematic review of the
effect of different overdenture attachments with different
implant loading protocols on peri-implant health is
lacking. Therefore, Aldhohrah et al192 conducted a sys­
tematic review and network meta-analysis to address the
focused question, “Which overdenture attachment and
loading protocol is associated with the lowest MBL, PD,
plaque index (PI), BOP, implant failure rate, and pros­
thodontic complications? A network meta-analysis
(NMA) compares three or more interventions in a single
analysis by combining direct and indirect evidence across
a network of studies, thus facilitating timely re­
commendations and reducing research waste.193,194
A comprehensive literature search extending to April
2020 was accomplished to identify eligible RCTs with at
least 10 participants per group, a minimum follow-up
period of 12 months, overdentures retained by 2-im­
plants, use of delayed loading (DL) or immediate
loading (IL) protocol and reporting the outcomes of
interest. The initial search yielded 1316 articles. After
text analysis, 16 RCT articles entered the review (599
participants and 1198 dental implants). These RCTs re­
ported on 5 standard overdenture attachment systems
(bar, ball, telescopic, magnetic, and LOCATOR) used
with delayed or immediate loading protocols. The risk of
bias was assessed using the Cochrane collaboration
tool149 (2 RCTs rated low risk, 4 rated high risk, and 10
rated unclear risk). The Bayesian NMA, accompanied by
a random effect model and 95% credible intervals, was
calculated.
Results indicated that MBL and PD were not sig­
nificantly different when comparing attachments with
loading protocols. The rank probability test showed
that bar+IL ranked highest (63.8%) in terms of MBL,
and ball+DL ranked highest (73.3%) in terms of PD.
The implant survival rate was 100% for LOCATOR
+DL, telescopic+DL, and magnet+IL. Survival rates
for other attachment+loading combinations included
99.1% for bar+DL, 98.8% for ball+DL, 96.0% for
magnet+ DL, 94.7% for LOCATOR+IL, 93.1% for ball
+IL, and 91.2% bar+IL. Regardless of the attachments
used, the implant survival rate for the delayed loading
protocol was 99.1%, and for the immediate loading
protocol was 95.3%.
The authors concluded that all overdenture attach­
ments reported here combined with immediate loading or
Cagna et al
467
delayed loading protocols had a similar effect on peri-
implant health. The bar+IL combination was associated
with the least MBL, whereas ball+DL showed the least
PD. Some peri-implant outcomes and prosthetic compli­
cations were inconclusive, perhaps because each attach­
ment system is associated with different complications.
Finally, the authors suggested that additional RCTs with
larger sample sizes and extended follow-up periods are
still needed to compare overdenture attachments with
varying loading protocols.
Stress/strain concentrations around implants may
lead to osseous microdamage resulting in peri-implant
bone loss. Studies have evaluated these stress con­
centrations around intentionally inclined implants
splinted with fixed cantilevered prostheses (all-on-4
treatment195). However, the stresses around in­
tentionally inclined implants supporting overdentures
with splinted and unsplinted attachment systems re­
quire investigation. Elhelbawy et al196 used strain gauge
analysis to record peri-implant strain development as­
sociated with resilient stud and bar attachments on in­
clined implants supporting mandibular overdentures
during loading and dislodging force applications in an in
vitro protocol.
A resin mandibular moderately atrophic edentulous
model was fabricated to include a resilient surface layer
to replicate the denture-bearing mucosa. Two vertical
implants in the canine sites and two 30-degree distally
inclined implants in the premolar sites were placed in
the model. For each implant, 3 strain gauges were
bonded to the buccal, lingual, and proximal peri-implant
surfaces. Overdentures were attached to the implants
with either a resilient stud attachment system
(LOCATOR; Zest, Group 1) or a Hader bar and yellow
plastic clip attachment system (RHEIN 83, Group 2)
attachment. Blue extra-light LOCATOR inserts were
used in canine (vertical) sites, and red extended-range
extra-light inserts were placed in premolar (inclined)
implant sites. The resulting strain was recorded during
vertical loading and dislodging force applications
(Material Testing Machine; Lloyd Instruments) to the
overdenture and compared between attachments (stud
versus bar) and implant trajectories (canine/vertical
versus premolar/inclined).
The results indicated that, for canine/vertical im­
plants during prosthesis loading, bar overdentures were
associated with significantly higher peri-implant mi­
crostrains than LOCATOR overdentures (P=.009). For
premolar/inclined implants during prosthesis dislod­
ging, LOCATOR overdentures were associated with
significantly higher peri-implant microstrains than bar
overdentures (P=.049). For both groups during pros­
thesis loading (LOCATOR P=.048; bar P=.004) and for
the bar overdenture group during prosthesis dislodging
(P=.045), canine/vertical implants were associated with
THE JOURNAL OF PROSTHETIC DENTISTRY
468
significantly higher peri-implant microstrains than pre­
molar/inclined implants.
The authors concluded that, within the limitations of
this in vitro investigation, the canine/vertical peri-im­
plant region might be subjected to increased stress
during prosthesis loading if bar attachments are used in
the modeled clinical situation. Additionally, if
LOCATOR attachments are used, the premolar/inclined
peri-implant region may risk increased stress when the
overdenture is dislodged. Finally, the peri-implant re­
gion of the canine/vertical implants may be over-
stressed during overdenture loading or dislodgement
when either attachment system is used.
The authors suggested that the absence of non-axial
loading in this in vitro protocol limits the interpretation
of results. In addition, the complex nature of functional
forces imparted to the prostheses under clinical condi­
tions is challenging to replication in a laboratory setting.
Therefore, future well-designed clinical trials are needed
to compare marginal bone levels associated with vertical
and inclined implants supporting mandibular over­
denture incorporating various attachment systems.
Implant fixed prosthodontics
It is generally believed that the intaglio surface of a
maxillary implant-supported fixed complete denture
should not present concavities, porosities, or a flange to
the edentulous tissues but should have a convex profile
with minimal residual ridge contact enabling ready ac­
cess by dental floss interdental brushes, and other per­
sonal oral hygiene devices. In addition, controlling
biofilm accumulation has been shown to reduce the
incidence of peri-implant disease. However, evidence-
based directives on how the shape of the intaglio surface
of these prostheses affects treatment outcomes are
scarce. Able et al197 reported on a cross-sectional study
that evaluated the shape (convex versus concave) of
maxillary implant-supported fixed complete denture
intaglio surfaces and associations with biofilm accumu­
lation, hyperemia, bone loss, and patient satisfaction.
The study participants included 56 patients (42
women, 14 men; mean age: 56 years; 388 implants;
mean time in place: 5.5 years; range: 1-14 years) with
maxillary implant-supported fixed complete dentures
(metal-resin design; resin intaglio surface contact) who
had attended follow-up appointments. The intaglio
surfaces were divided into cantilever and inter-implant
regions (n=442). Each region became a unit of analysis
and was assessed for shape (concave or convex) and
biofilm index (0 to 3). The shape was assessed by
stretching dental floss across the intaglio surface, from
facial to palatal. Tissue hyperemia or redness was as­
sessed (absent or present), and crestal bone loss was
measured (mm) by 2 calibrated evaluators
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Volume 130 Issue 4
(kappa=94.9%). Patient satisfaction was recorded using
a questionnaire with a visual analog scale.
Of the 442 analyzed intaglio regions, 58 (13.1%) were
concave, and 384 (86.9%) were convex. Biofilm was absent
in 3.5% of the concave and 5.5% of the convex regions.
Biofilm was detectable with a probe in 12% of the concave
and 22.4% of the convex regions and clinically visible in
58.6% of the concave and 57.8% of the convex regions.
Abundant biofilm was seen on 25.9% of the concave and
14.3% of the convex regions and was associated with
hyperemia (P=.003). A statistically significant association
was found between the intaglio surface shape and biofilm
accumulation (P=.009). Hyperemia was present in 199
(45%) regions. The association analysis between the re­
gion shape and the presence of hyperemia was not sig­
nificant (P>.05). The mean bone loss was 0.71 mm
(±0.91 mm). Implants placed near concave regions de­
monstrated greater bone loss (P=.001). Study participants
reported high satisfaction (62.5 to 73.2%) with the pros­
thesis's esthetic, mastication, and phonetic aspects.
However, only 19.6% were fully satisfied related to ease of
cleaning.
The authors concluded that the shape of the intaglio
surface of maxillary implant-supported fixed complete
denture influenced the occurrence of biological compli­
cations, with concave regions being associated with
more significant biofilm accumulation and crestal bone
loss. Patients were very satisfied with prosthesis es­
thetics, mastication, and phonetics but were generally
dissatisfied with the ease of cleaning.
Since its inception, the all-on-4 treatment concept195
for complete and immediate complete arch implant-
supported rehabilitation has offered predictable medium-
and long-term outcomes in the mandible and maxilla.
Using a series of implants intentionally placed with axial
and tilted orientations takes advantage of available bone
to optimize mechanical support and minimize augmen­
tation surgeries and costs. Periodic reassessment of this
treatment concept is prudent. Therefore, Del Fabbro
et al198 reported on a systematic review and meta-ana­
lysis that provided an up-to-date comprehensive perfor­
mance evaluation of fixed mandibular and maxillary
complete dentures supported by axial and tilted implants
after at least 3 years of follow-up.
Initially, an electronic and manual literature search
extending to April 2021 identified 824 articles. Applying
exclusion criteria and text analysis yielded 24 reports
that entered the review. Study quality was determined
using the Cochrane assessment tool for RCTs149 and
the Joanna Briggs Institute tool for cohort and case
series investigation.155 Bias was identified as low in 8
studies, moderate in 8, high in 6 (including 2 RCTs), and
serious in 2.
The outcomes of interest were cumulative implant
survival rate, marginal bone level changes, and
Cagna et al
October 2023
complications. The difference in outcomes for implant
trajectory (axial versus tilted) and restored arch (maxilla
versus mandible) were assessed in the meta-analysis.
The review included 2637 patients, 2735 prostheses
(1464 maxillary; 1271 mandibular), 5594 tilted implants,
and 5611 axial implants. Treatment follow-up ranged
between 3 and 18 years, during which 274 implants
failed. The cumulative implant survival rate was 93.91%
(95% CI: 92.01-95.37%) up to 18 years of follow-up.
Assessment of implant failures over time revealed that
41.6% occurred within the first year. The cumulative
prosthesis survival rate was 99.31% (implant losses: 11
maxillary, 8 mandibular) which was not different be­
tween arches (P=.70).
The mean marginal bone level change was moderate,
exceeding 2 mm in only 2 studies with more than 5 years
of follow-ups. MBL was less around the axial compared
with tilted implants (P<.001) and was not affected by the
arch restored (P=.17).
The most common prosthodontic complications were
screw loosening, interim restoration fracture, and chip­
ping, wear, and discoloration of acrylic resin. The most
frequently reported biological complications included
mucositis, peri-implantitis, abscess or suppuration, and
fistula formation. Five studies reported the absence of
biological complications.
Based on this systematic review and meta-analysis
that included clinic follow-ups from 3 to 18 years, the
authors concluded that fixed complete dentures sup­
ported by tilted and axially placed implants represent a
predictable option for rehabilitating edentulous arches.
However, additional RCTs with large sample sizes are
needed to determine the efficacy of this treatment ap­
proach, including the remodeling of marginal bone, in
the long term.
Modern-day implant dentistry generally offers reli­
able and predictable solutions for restoring missing
teeth. However, reestablishing ideal esthetics when
implants replace missing maxillary anterior teeth can be
challenging, particularly when tooth and periodontal
tissues must be maintained or restored. Luo et al199
evaluated the esthetics of the interproximal papilla be­
tween implant-restored unilateral and bilateral maxillary
central incisors.
Using a cross-sectional study design, retrospective
enrollment of 56 adults with maxillary central incisor
implant restorations (bone-level platform switched im­
plants, delayed placement, delayed restoration) included
40 patients with unilateral (1 implant) and 16 patients
with bilateral (2 implants) central incisor replacements.
The unilateral and bilateral groups were characterized by
similar age (P=.596), sex (P=.863), implant system
(P=.064), abutment type (P=.495), and crown material
(P=.372). The mean follow-up time was 23.2 months
(23.2 months for unilateral and 23.1 months for bilateral).
Cagna et al
469
Primary outcomes were the papilla index and pa­
tient-reported esthetic satisfaction. Secondary study
outcomes included clinical and radiographic variables
associated with incomplete papilla fill.
Intraoral photographic and standardized radio­
graphic assessments were performed to evaluate midline
papilla fill and underlying bone dimensions. Patient-
reported esthetic satisfaction was recorded using a
questionnaire with a visual analog scale.
The results indicated that the papilla index in the
unilateral group was superior to the bilateral group
(P=.002), although patients in both groups reported equal
esthetic satisfaction (P=.470). Significant differences be­
tween groups were noted in papilla height (P<.001),
implant-to-implant or implant-to-tooth distance
(P=.002), and vertical implant platform-to-bone crest
distance (P<.001). In the bilateral group, tested variables
were not correlated with the papilla index. In the uni­
lateral group, incomplete papilla fill was associated with
abutment type (OR=.019), implant-to-tooth distance
(OR=6.435; range: 2.1-6.2 mm), and bone crest-to-con­
tact point (OR=-4.589; range: 3.5-6.9 mm).
The authors concluded that for implant-restored
maxillary central incisors, midline papilla fill was su­
perior for unilateral compared with bilateral implant
restorations. No clinical variable studied was correlated
with the papilla index for bilateral central incisor re­
storations. For the unilateral central incisor restorations,
the risk of incomplete papilla fill was reduced in the
presence of custom zirconia abutments. It was increased
by greater implant-to-tooth distance and greater bone
crest-to-contact point distance.
Next, a series of 4 articles reporting on proximal
contact loss (PCL) involving implant restoration in par­
tially edentulous patients will be presented. PCL has been
reported as a possible post-treatment complication that
occurs when the proximal contact between a fixed pros­
thodontic restoration and the adjacent tooth opens.
Factors suggested to influence PCL include, but may not
be limited to, craniofacial growth, tooth movement or
mesial drift phenomenon, the anterior component of
occlusal force, changes in biofunctionality (mastication
patterns), occlusal load sharing between teeth and im­
plant restorations, parafunctional habits, proximal surface
wear, opposing restorations/occlusion, arch stability,
periodontal status, history of orthodontic therapy, pre­
ferred side for mastication, and aggressive interproximal
personal hygiene methods.
Regardless of etiology, the consequences of PCL can
adversely affect peri-implant and periodontal hard and
soft tissue health and cause significant patient discomfort
from food impaction. To better understand PCL,
Manicone et al200 conducted a systematic review and
meta-analysis designed to estimate the overall prevalence
of PCL and determine the distribution of associated
THE JOURNAL OF PROSTHETIC DENTISTRY
470
clinical features. The primary outcome was the occurrence
of PCL. The secondary outcomes involved the location of
PCLs, including mesial or distal (PCLM or PCLD) and
mandible or maxilla (PCLMax or PCLMand).
An electronic and manual literature search extending
to November 2020 initially identified 831 articles. Applying
exclusion criteria and full-text analysis resulted in the en­
rollment of 15 articles in the systematic review (10 retro­
spective; 5 prospective; 11 699 implant restorations) and 10
articles in the meta-analysis. The quality of included stu­
dies was assessed using the JBI critical appraisal check­
list.155 Study quality was generally moderate since most
of the included articles used insufficient sample sizes
to define PCL prevalence, and most used retrospective
designs. There was high heterogeneity across studies
(I2: 96% to 98%).
The overall prevalence of PCL was 20% at the im­
plant restoration level (among 4984 implant restora­
tions) and 26.6% at the contact point level (among 2603
contact points). Mesial PCL prevalence was more fre­
quent at restoration (13.8%) and contact point (21.9%)
levels. Distal PCL prevalence at the restoration (3.3%)
and contact point (11.0%) levels was less. The rate of
PCL in the maxilla (21.4%) and mandible (21.9%) at the
contact point level were similar. The random effects
meta-analyzed proportions were 32.5% (PCL), 23.4%
(PCLM), and 11.0% (PCLD) at the implant restoration
level, and 29.1% (PCL), 23.1% (PCLM), and 8.7%
(PCLD) at the contact point level (P<.01).
Most included articles related PCLs to patient com­
plaints of food impaction. Also, a correlation was seen
between PCLs and adjacent tooth defects, peri-implant
tissue inflammation, more significant proximal bone
loss, and elevated PI. PCLs were more common with
extended duration restoration function. Several articles
indicated that PCL incidence peaked at 2 years, while
others reported 5 years.
The authors concluded that PCL is a frequent and
poorly understood complication. Approximately 29% of
implant restoration contact points develop this condi­
tion, which is more likely to affect the mesial contact.
Patient discomfort, food impaction, and damage to the
interproximal tissues may result.
A second study addressing PCL was reported by
Bompolaki et al201 This was a retrospective cross-sec­
tional study investigating the effect of PCL on peri-im­
plant tissue health and patient awareness of the
associated food impaction. The study also sought to
identify patient or local factors that could cause inter­
proximal contact loss.
Participants included 83 adults (29 men; 54 women,
age: 63 ±11.4 years; range 37-86 years) who received
posterior single-unit implant-supported screw-retained
metal-ceramic or cast metal restorations between 2005
and 2015. Waxed dental floss was used to evaluate
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restored interproximal contacts at the time of placement;
contacts were present (moderate to heavy floss re­
sistance) per treatment documentation.
The mean follow-up time after restoration placement
was 4 ±2.2 years (range: 4 months to 10.6 years). A
single recall visit was used, and interproximal contacts
were evaluated using waxed dental floss. If a contact was
absent, layers of 12-µm shim stock were used to mea­
sure the space. Patient age, sex, implant location, op­
posing tooth status, adjacent endodontically treated
teeth, and use of a nocturnal occlusal device were re­
corded. In addition, peri-implant PD and BOP were
recorded, and participants were asked to comment on
food impaction around the implant restorations.
The results indicated that among the mesial contacts
examined, 34.1% were open. The incidence of mesial PCL
(“open” and “loose” combined) was 48.8%. Among the
distal contacts examined, 10% were open, with a PCL
incidence of 26.7%. As measured with layered shim stock,
the average dimension of mesial PCL was 98.76 µm, and
distal PCL was 65.64 µm. This difference was significant
(P<.001). Premolar restorations exhibited tighter mesial
interproximal contacts than molar restorations (U=566;
P=.041), and a negative correlation was found between
post-placement follow-up time and mesial contact
tightness (rs=-0.226; P=.041). For those with PCL, 43.8%
reported awareness of food impaction in the affected
area. PCL was not associated with age, endodontically
treated adjacent teeth, jaw, opposing tooth status, or use
of an occlusal device.
The authors concluded that PCL appears to increase
over time, with more surfaces affected after extended
periods of restoration service. This study found a limited
association between PCL and peri-implant inflamma­
tion (BOP). The study participants were more aware of
food impaction around their implant crowns, and using
an occlusal device did not prevent PCL. Research into
the prevention and management of PCL is strongly re­
commended since it appears to be a prevalent technical
complication affecting fixed implant restorations ad­
jacent to natural teeth.
In a third interesting report, Yen et al202 stated that
the currently suggested high prevalence (34% to 66%) of
PCL does not match their experience. More importantly,
potential implant prosthodontic factors contributing to
PCL are seldom reported. To address these concerns,
they conducted a retrospective clinical study to examine
follow-up radiographs of implant-supported fixed par­
tial restorations (ISFPRs or crowns and FPDs) to de­
termine the prevalence of PCL between ISFPRs and
adjacent teeth and to assess the risk factors associated
with PCL at the patient, implant restoration, and ad­
jacent tooth levels.
Patients treated with ISFPRs (147 patients; 180
ISFPRs; 296 interproximal contacts) between January
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October 2023
2007 and December 2016 were included. Twenty-six
participants had 2 or more ISFPRs. Digital radiographs
obtained at restoration placement and subsequent
follow-up were assessed. The prevalence of PCL and
associated risk factors at the patient level (age, sex,
diabetes, smoking, and bruxism), ISFPR level (follow-up
period, arch location, splinting, materials, screw or ce­
ment retention, and fixture-implant connection geo­
metry), and adjacent tooth level (mesial or distal side,
proximal contact material, vitality, bone height, and
contralateral spacing) were analyzed (α=.05).
The results revealed that PCL onset was 6
to 96 months after ISFPR placement. The prevalence of
PCL was 15% (patient level), 13.3% (ISFPR level), and
8.8% (adjacent tooth level).
Significant risk factors for PCL were identified at all
levels investigated, including the patient level (sex), the
ISFPR level (longer follow-up period; external hexagonal
connection geometry, internal octagonal connection
geometry), and the adjacent tooth level (contralateral
spacing, composite resin proximal contact, mesial side).
Contralateral spacing (OR=20.88; P=.002) and mesial
proximal side (OR=13.10; P<.001) had the highest ad­
justed odds ratio.
The authors concluded that most PCLs were found at
the mesial side of ISFPRs, and the odds of experiencing a
PCL were significant for participants with longer follow-
up periods. Internal hexagonal implant-abutment con­
nections were at lower risk for PCL than other geometries.
Factors relevant to the anterior component of occlusal
force (male sex, contralateral spacing at the adjacent tooth,
and proximal contact of ISFPR with composite resin) seem
to be high-risk factors for PCL. Food impaction and peri-
implant tissue problems were noted, although the bone
height was not affected. The authors suggested that PCL
could be a sign of unstable occlusion, which may subse­
quently lead to mechanical complications.
The final look at this topic in the present review
addresses PCL recurrence after an intervention to re­
store the missing proximal contact. Liang et al203 con­
ducted a retrospective study to evaluate the recurrence
rate of PCL and potential risk factors of PCL recurrence.
This retrospective study included 41 patients (45 im­
plants), who had experienced PCL between posterior
implant restorations and adjacent teeth, and subsequently
received proximal contact repair (“soft” repair with com­
posite resin versus “firm” repair with porcelain additions
or crown placement/replacement). PCL recurrence, rate,
and time were recorded during routine follow-up visits.
Statistical analysis assessed related factors.
Results demonstrated that mesial PCL recurrence
rates were high (>50%), and recurrence time became
progressively rapid (sequentially 5, 3.2, and 2.2 years)
after each repair. Furthermore, restorations involved in a
PCL recurrence were more likely to be splinted than
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471
restorations without a recurrence (54.5% versus 18.8%;
P=.032). Additionally, patients experiencing a recurrence
were older than those without recurrence (55.8 versus
50.1 years; P=.087).
The patient factors of age, restoration design (splinted
versus single), frequency of interdental brushing, and
time to initial complaint were associated with recurrent
PCL. However, only implant restoration splinted design
was independently associated with a higher risk of PCL
recurrence (OR=4.99; 95% CI: 1.02-24.31; P=.047).
The authors concluded that mesial PCL recurrence
rates were high and associated with the splinted re­
storation design. Also, the recurrence time for PCL ac­
celerated after each repair. Therefore, routine follow-up
monitoring of PCL and careful assessment of patient
compliance are essential.
Prosthodontic materials
The foundation of all high-quality prosthodontic re­
storations is firmly based in materials science. As digital
technology moves further into prosthodontics, a new
wave of materials requires evaluation and optimization.
Knowing where the profession stands with existing di­
gital processes is essential. Al Hamad et al204 reported
on a systematic review and meta-analysis addressing 2
PICO questions. The main question was, “What are the
outcomes of using additive manufacturing (AM) com­
pared with subtractive manufacturing (SM) for the fab­
rication of dental ceramic restorations?” A second
focused question was, “Does the type of printer tech­
nology influence the outcome of the fabricated dental
ceramics?”.
An electronic literature search extending to February
2022 initially identified 1833 articles. Applying exclusion
criteria and full-text analysis resulted in the enrollment
of 28 articles in the systematic review (3 domains: ac­
curacy – 11 in vitro studies; color and esthetics – 1
clinical trial; physical/mechanical properties – 16 in vitro
studies) and 14 articles in the meta-analysis. Two ma­
terials (zirconia and alumina), 3 restoration types (single
crowns, occlusal veneers, and FPDs), and 3 AM tech­
nologies (digital light processing or DLP, selective laser
melting or SLA, and self-glazed zirconia or SGZ) were
reported. Quality assessment of the included studies was
performed using the JBI risk of bias assessment tool for
quasi-experimental studies.205
For accuracy, the meta-analysis showed overall
higher accuracy for SM (compared with AM) with
medium effect size (g=0.679; CI: 0.173 to 1.185; P=.009),
including margin accuracy (g=1.05; CI: 0.344 to 1.760;
P=.004), occlusal accuracy (g=2.24; CI: 0.718 to 3.766;
P=.004), and total overall accuracy (g=4.544; CI: -0.234
to 9.323, P=.062) with large effect size. AM had higher
accuracy (compared with SM) for the external surface
THE JOURNAL OF PROSTHETIC DENTISTRY
472
accuracy (g=-0.238; CI: -1.215 to 0.739); P=.633) and
internal surface accuracy (g=-0.403; CI: -1.273 to 0.467;
P=.364) with small effect size.
For physical or mechanical properties, flexural strength
was higher for ceramics made by SM (in comparison to
AM) with a large effect size (g=-2.868; CI: -4.371 to -1.365;
P<.001). All studies on accuracy and physical/mechanical
properties were in vitro, with high heterogeneity and low
to very low certainty of evidence.
For printer technology, the self-glazed zirconia
(SGZ) protocol had the smallest effect size (g=-0.049; CI:
-0.878 to 0.78, P=.907), followed by stereolithography
(g=0.305; CI: -0.289 to 0.9; P=.314), and digital light
processing (g=1.819; CI: 0.662 to 2.976; P=.002) tech­
nologies. Only 1 study reported on color. It favored SGZ
ceramics made through combined SM (milled cavity
mold) and AM (3D gel deposition of colloidal zirconia).
The authors concluded that SM had better overall
accuracy, particularly for the marginal and occlusal
areas, higher flexural strength, and more favorable
hardness, fracture toughness, porosity, fatigue, and vo­
lumetric shrinkage. AM had a more favorable elastic
modulus and wettability. Compared with DLP, higher
accuracy is achieved with the AM technologies of SGZ
and SLA. Both manufacturing methods had favorable
biocompatibility. All studies on accuracy and mechanical
properties were in vitro, with high heterogeneity and
low to very low certainty of evidence due to study type,
imprecision, and inconsistency, and were highly het­
erogeneous due to different study outcomes, research
methodologies, materials, and AM technologies. There
is a lack of studies investigating color and esthetics
produced by AM.
Translucent dental zirconia (5-mol% yttria-stabilized
tetragonal zirconia polycrystal or 5Y-TZP) offers desir­
able esthetic characteristics compared to the more
common dental zirconia variant 3Y-TZP. Gaining
translucency by doping zirconia with 5 mol% yttria may
reduce mechanical properties critical to material per­
formance. Whether the clinically relevant mechanical
property of the edge chipping toughness of this material
is reduced remains unclear. Flask et al206 evaluated the
edge-chipping toughness and translucency of translu­
cent zirconia, 3Y-TZP, and lithium disilicate.
Two translucent zirconia products (Katana UTML;
Kuratay Noritake Dental and Lava Esthetic; 3M ESPE),
one 3Y-TZP (Lava Plus; 3M ESPE), and one lithium
disilicate (IPS e.max Press; Ivoclar AG) were processed
and prepared according to manufacturer’s specifications.
The 3Y-TZP served as the optimal control material for
edge chipping and the lithium disilicate for translucency.
The resulting specimens were prepared and tested
for phase composition (X-ray diffraction; n=3), translu­
cency (spectrophotometer; n=20), and edge chipping
(universal testing machine; n=20). Each specimen was
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Volume 130 Issue 4
fixed in a universal testing machine equipped with a
sharp diamond-tip conical indenter for edge chipping.
Force was applied to the sample between 0.1 and
1.0 mm from the specimen’s edge. Two edge chipping
tests were performed on each specimen at opposite
edges. A 0.1 mm/min crosshead speed was used, and
the maximum load (N) to ceramic chipping was re­
corded (n=40). The distance from the specimen’s test
edge to the indenter’s point of contact was recorded.
X-ray diffraction showed the 3Y-TZP to be a pri­
marily tetragonal phase (96.5%) compared with the 2
translucent zirconia products that were predominantly
cubic (59% for Lava Esthetic; 73% for Katana UTML).
Furthermore, Katana UTML and IPS e.max Press had
similar translucency (P>.05) that was greater than that of
Lava Esthetic and Lava Plus (P<.05). The edge tough­
ness of Katana UTML was 304 N/mm, IPS e.max Press
was 354 N/mm, Lava Esthetic was 394 N/mm, and Lava
Plus was 717 N/mm, with significance rankings (P<.05)
as follows, Katana UTM<IPS e.max Press=Lava
Esthetic<Lava Plus.
For the materials tested, the authors concluded that
edge toughness decreased as translucency increased
with increased cubic content. The conventional 3Y-
TZP product tested maintains a clear advantage in
edge toughness, while the translucent products show
an edge toughness closer to lithium disilicate.
Additionally, some translucent zirconias appear to
have translucency like lithium disilicate. The authors
suggested that “translucent zirconia” may be too
broad. It may be more appropriate to refer to these
materials by the percentage of each phase present so
that a clinician can better predict expected optical and
mechanical properties.
Digital printing and printable denture base resins are
in a continuous state of evolution. However, studies
investigating the mechanical and surface properties of
printed denture base materials compared with conven­
tional heat-activated denture base acrylic resins are
limited. Therefore, Gad et al207 conducted an in vitro
protocol to evaluate and compare the flexural strength,
impact strength, hardness, and surface roughness of
printed denture base resin before and after being sub­
jected to thermal cycling treatment.
According to the International Organization for
Standardization (ISO) 20795-1:2013 standards,208 120
acrylic resin specimens (40 for flexural strength testing,
40 for impact strength testing, and 40 for surface
roughness and hardness testing) were fabricated and
distributed into two groups: heat-activated acrylic resin
(control group; Major.Base.20, Major Prodotti Dentari
SPA) and printed acrylic resin (experimental group;
Denture 3D+, NextDent BV). Half of the specimens in
each group were subjected to 10 000 thermal cycles
between 5 °C and 55 °C (5 s transfer, 30 s dwell time),
Cagna et al
October 2023
simulating 1 year of clinical use. Flexural strength (MPa)
was measured by using a universal testing machine. A
Charpy impact tester was used to record impact strength
(KJ/m2). Resin hardness (VHN) and surface roughness
(μm) were also measured. The resulting data were
analyzed (α=.05).
The results indicated significant differences between
heat-activated and printed resin for flexural strength
(86.63 ±1.0 and 69.15 ±0.88 MPa), impact strength
(-6.32 ±0.50 and 2.44 ±0.31 KJ/m2), hardness
(-41.63 ±2.03 and 34.62 ±2.1 VHN), and surface
roughness (-0.18 ±0.01 and 0.12 ±0.02 µm), respectively
(P<.001). In addition, thermal cycling significantly de­
creased (P<.001) printed resin flexural strength
(63.93 ±1.54 MPa), impact strength (2.40 ±0.35 KJ/m2),
and hardness (30.17 ±1.38 VHN), but surface roughness
remained unchanged (P=.262).
For the materials test here, printed denture base resin
had inferior flexural strength, impact strength, and
hardness values compared with heat-activated denture
base resin but showed superior surface roughness
properties. Temperature changes (thermal cycling) sig­
nificantly reduced printed resin hardness and flexural
strength and increased surface roughness but did not
affect the impact strength.
Although the printed denture base resin material
investigated here demonstrated inferior flexural
strength, the value recorded met the ISO requirement of
65 MPa.208 However, the average flexural strength de­
creased after thermal cycling below the required value,
raising concern about the clinical performance of the
printed resin in the oral environment.
Wax pattern development and lost-wax casting have
been the traditional process for fabricating RPD frame­
works. However, this process is time-consuming, labor-
intensive, and technique sensitive. Other manufacturing
challenges include high melting ranges of the metal al­
loys, clinically demanding casting accuracy, and diffi­
culty controlling metal alloy mechanical properties.
Recently, selective laser melting (SLM), an additive
manufacturing method, has been introduced as an al­
ternative for fabricating base metal alloy RPD frame­
works. However, the physical properties of the alloys
involved are not well understood. To evaluate and
compare the mechanical properties and structural
characteristics of cobalt chromium (Co-Cr) RPD alloy
specimens produced by SLM, SLM with heat treatment
(SLM-H), or lost-wax casting (CA), Lee et al209 reported
on an in vitro trial.
Dumbbell specimens and RPD frameworks (man­
dibular posterior Kennedy Class III sextant model) were
fabricated. Following the SLM processes, specimens in
the SLM-H group were subjected to heat treatment in a
furnace with high-purity argon. First, specimens were
heated from room temperature to 1150 °C at a ramp rate
Cagna et al
473
of 10 °C/min and held at that temperature for 6 h in the
furnace. Then, heat-treated specimens were slowly
cooled to room temperature. The effects of the heat
treatment on the alloy microstructure were studied using
optical microscopy (OM), scanning electron microscopy
(SEM), and X-ray diffraction (XRD).
Tensile testing on dumbbell specimens was per­
formed in a universal testing machine (5 mm/min
crosshead speed) and resulting stress-strain curves were
used to assess ultimate tensile strength (UTS), 0.2%
yield strength (0.2% YS), and elongation (E). Fractured
surfaces were observed with SEM. An insertion/removal
test with the model and RPD frameworks mounting in a
micromechanical testing machine (60 mm/min cross­
head speed) was used to measure retentive force.
Specimens fabricated using the lost-wax process (CA
group) served as controls. Data were subjected to sta­
tistically analyzed (α=.05).
Results indicated that different manufacturing
methods yielded different microstructures. X-ray dif­
fraction revealed that the γ (face-centered cubic) phase
dominated SLM and SLM-H specimens, and the CA
group exhibited a mixture of γ and ε (hexagonal close-
packed) phases. Optical microscopy and SEM showed
microstructural changes under different fabrication and
postprocessing heat treatments. Observing the grain
boundary in the SLM group was difficult, whereas sub-
micrometer-scale grains had formed in the SLM-H
group. The CA group generally demonstrated relatively
brittle behavior and limited plastic deformation. The
SLM group exhibited higher strength than the CA
group, whereas the SLM-H group revealed greater
elongation and retentive force than the SLM and CA
groups.
The authors concluded that the SLM increased the
mechanical properties of Co-Cr alloys compared with
traditional CA processing. Post-processing heat treatment
(SLM-H) changed the brittle phase, further enhancing the
alloy's tensile ductility. The authors suggested that SLM
followed by heat treatment, is an efficient strategy for
fabricating RPD frameworks. However, heat treatment
optimization, the marginal fit of SLM-fabricated RPD
frameworks, and plastic deformation after cyclic removals/
insertions require further investigation.
PERIODONTICS, ALVEOLAR BONE, AND
PERI-IMPLANT TISSUES
This year’s review covered topics relating to the etiology,
diagnosis, and prevalence of periodontal disease, the
systemic health relationships with the periodontium,
periodontal treatment therapies, the soft tissues adjacent
to teeth and implants, the biology of alveolar bone and
osteonecrosis of the jaw, alveolar ridge preservation,
THE JOURNAL OF PROSTHETIC DENTISTRY
474
alveolar bone and sinus augmentation techniques, and
peri-implant diseases.
Periodontal disease etiology, diagnosis, and
prevalence
Periodontal disease remains a significant public health
problem, with severe periodontitis estimated to affect
nearly 11% of the global population and the sixth most
common human disease. Significant socio-economic
impacts are a result. Botelho et al210 conducted a study
estimating the direct and indirect economic burdens of
periodontal disease in the US and Europe using the
most recent available data to estimate the cost of peri­
odontal disease. Global health, dental and periodontal
expenditures were assessed by examining the direct and
indirect costs of periodontitis. Indirect costs were de­
fined as those related to productivity losses due to per­
iodontal disease proper, plus edentulism and caries
because of periodontal disease. They found that in 2018,
the aggregate direct costs in the US were estimated at
$3.49B and €2.52B in Europe. Indirect costs because of
periodontal disease amounted to $150.57B in the US and
€156.12B in Europe. Most of the projected indirect costs
were because of edentulism related to periodontal dis­
ease, with an average of 0.73% of the annual gross
domestic product in the US and 0.99% in Europe.
Recent studies have illuminated previously unknown
aspects of periodontal disease pathogenesis. It is well
known that macrophages are a significant part of the
inflammatory process. They are immune cells formed in
response to an infection or an accumulation of damaged
cells. Macrophages that encourage inflammation are
called M1 macrophages, and those which decrease in­
flammation and facilitate tissue repair are called M2
macrophages. The balance between M1 and M2 mac­
rophages is essential for regulating immune responses
with tissue repair processes.
Although the presence of telocytes has been known
for many years, their function has been controversial.
Telocytes have recently gained prominence by dis­
covering their presence in many different tissues and
their role in structural support and cell-to-cell commu­
nication. Telocytes have long been postulated to be es­
sential for cell-to-cell signaling with their surrounding
cells. Telocytes make many direct contacts with neigh­
boring cells by gap junctions, which allow molecules and
ions to pass through between two cells. Telocytes have
also been proposed to be involved in regulating immune
responses.
Using scRNA sequencing techniques and lineage
tracing, Zhao et al211 identified telocytes and macro­
phages in mouse periodontium in homeostasis and
periodontitis. They demonstrated that telocytes are
quiescent in homeostasis. In periodontitis, however, the
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
telocytes proliferate. Of significance, Zhao et al2 de­
monstrated that macrophages receive telocyte-derived
signals and induce a shift from an M1 to an M1/M2
state. The role of telocytes in regulating macrophage
behavior in periodontitis may provide a future approach
to treating periodontitis.
The successful management of periodontal disease
partially depends upon the accurate and timely diagnosis
of the disease before or early in the pathologic process of
periodontal attachment loss. While examining each pos­
sible disease site and documentation of attachment levels
with clinical findings remains the standard, using bio­
markers for active periodontal disease before attachment
loss would be ideal.
In the last few years, increasing evidence has reported
an important role played by a complex of nucleotide-
binding and oligomerization domain (NOD)-like receptor
(NLR) complexes defined as an “inflammasome” during
the early stages of the innate immune response.
Specifically, the Nod-like receptor family pyrin domain-
containing protein-3 (NLRP3) complex inflammasome
has been shown to play an important role in developing
periodontitis and diabetes. Isola et al212 examined the
association between serum and salivary NLRP3 con­
centrations in patients with periodontitis and type 2
diabetes mellitus (DM) and evaluated whether potential
confounders influenced this association. The 4 groups of
patients included healthy controls, type II diabetics (DM),
active periodontitis patients, and those with both peri­
odontal disease and DM. Univariate and multivariate
models were formulated to analyze whether periodontitis
and type-II DM influenced serum and salivary NLRP3
concentrations. The authors demonstrated that compared
to type 2 DM patients and healthy controls, patients with
periodontitis had elevated serum and salivary NLRP3
concentrations. NLRP3 may be a promising biomarker of
disease risk in patients with periodontitis and type 2 DM.
Grant et al213 also examined the use of biomarkers in
the saliva and gingival crevicular fluid to discriminate
objectively between periodontal health and plaque-in­
duced periodontal disease states. One hundred and
ninety participants were recruited from 2 centers com­
prising healthy, gingivitis, periodontitis, and edentulous
patients. Samples were analyzed by quantitative mass
spectrometry proteomics for biomarker discovery. Short­
listed candidate proteins were then verified by enzyme-
linked immunosorbent assay. Ninety-five proteins were
identified in both GCF and saliva samples, and 15 can­
didate proteins were selected. The best-performing pa­
nels distinguishing between health or gingivitis and
periodontitis contained matrix metalloproteinase-9
(MMP9), S100A8, alpha-1-acid glycoprotein (A1AGP),
and pyruvate kinase. This biomarker panel, composed of
these 4 proteins, can distinguish between periodontal
health and disease states.
Cagna et al
October 2023
Periodontal diseases and systemic health
relationships
Although the relationship is not fully clarified, current
evidence supports the association between OSA and
periodontitis. However, the lack of control of potential
confounders, sample size estimations, and different di­
agnostic procedures for clinical assessment of the pre­
sence and severity of both periodontitis and OSA
obscures the identification of definitive causalities. In
addition, OSA and periodontitis share similar environ­
mental and systemic risk factors. Therefore, controlling
these risk factors is imperative during clinical trials ex­
amining the relationship between periodontal disease
and OSA. Likewise, establishing clear definitions of
OSA and periodontitis is essential in data analysis.
The American Academy of Periodontology recently
established a more precise staging and definition of
periodontal disease. Stazić et al214 conducted a cross-
sectional study using these updated staging classifica­
tions for periodontitis. They investigated the stages of
periodontitis in patients with OSA and the risk factors
associated with periodontitis severity among them. One
hundred and ninety-four patients underwent poly­
somnography/polygraphy to determine their AHI and
were referred for periodontal examination. Patients were
classified as mild OSA (AHI <15) or moderate to severe
OSA (AHI>/=15), whereas periodontitis severity was
determined by the clinical attachment level (CAL). Pa­
tients were grouped into 2 periodontal categories: stages
1 and 2, and stages 3 and 4. Higher AHI values were
reported in OSA patients exhibiting periodontitis stages
3 and 4 compared to those with periodontitis stages 1
and 2, and the non-periodontitis group. Also, a positive
correlation was found between AHI and mean CAL, and
between AHI and plaque scores. A multivariable re­
gression analysis found AHI to predict mean CAL sig­
nificantly. OSA was also associated with severe stages of
periodontitis, increased age, smoking, low frequency of
dental visits, and poor oral hygiene.
Severe OSA and peritonsillar infections are fre­
quently treated with tonsillectomy in younger patients.
In the short term, tonsillectomy effectively treats OSA
and tonsillar infections. However, by removing these
lymphoid organs, tonsillectomies might alter the sys­
temic immune system, eventually affecting the patient’s
response to periodontitis. Ma et al215 conducted a study
investigating the association between tonsillectomy and
periodontitis using a large national health system da­
taset. Data were collected from the Taiwan Longitudinal
Health Insurance Dataset from 1999 to 2013. A total of
1482 tonsillectomy cases and 14 796 non-tonsillectomy
controls were selected. A total of 648 patients who had
undergone tonsillectomy and 648 out of 6509 propensity
score-matched controls were retrieved, among which
Cagna et al
475
230 cases in the tonsillectomy group were associated
with post-surgical periodontitis. The association per­
sisted in a subpopulation of patients with periodontitis
who received mechanical and surgical treatments for
periodontitis. The incidence of periodontitis was sig­
nificantly high in the individuals who underwent ton­
sillectomy and particularly in those below 12 years of
age. Of interest is that most post-tonsillectomy period­
ontitis cases were of an aggressive form and developed
on average four years after tonsillectomy.
It has been demonstrated that patients with period­
ontitis have a higher incidence for the coexistence of H.
pylori in the dental plaque and the stomach. Poor oral
health may induce the dysbiosis of H. pylori in the oral
cavity, which is potentially a source of transmission or
reinfection of the gastrointestinal (GI) tract. H. pylori has
also been associated with many GI tract cancers. Sung
et al216 examined the association between periodontitis
and survival outcomes in individuals concerning H. py­
lori infection. They studied a population of 4955 subjects
aged 20-90 who had received both periodontal ex­
amination and H. pylori serum test in the Third National
Health and Nutrition Examination Survey (NHANES III)
database. It was demonstrated that periodontitis was
significantly associated with increased odds of H. pylori
infection and increased mortality risk from all causes. In
addition, periodontitis was significantly related to the
decreased survival time in subjects with GI tract or
colorectal cancers and a concomitant H. pylori infection.
Rheumatoid arthritis (RA) is a chronic inflammatory
autoimmune disease primarily resulting in polyarthritis
of the small joints. Meta-analyses have previously
shown an association between periodontitis and RA.
This association between a history of periodontitis and
RA risk is both dose-and time-dependent. Considering
that periodontitis plays a role in the development of RA,
a similar association may be present with systemic lupus
erythematosus (SLE). To date, there is limited research
regarding periodontitis in SLE patients. Bolstad et al217
examined the association between SLE and periodontitis
in Norwegians over 10 years. In this large population-
based study, 1990 patients were included in the SLE
cohort based on diagnostic codes registered in the
Norwegian Patient Registry. The control group (n=170
332) comprised patients registered with diagnostic codes
for non-osteoporotic fractures or hip or knee replace­
ment because of osteoarthritis. Using procedure codes
registered for periodontitis, logistic regression analyses
were performed to estimate the odds ratio for period­
ontitis in patients versus controls adjusted for potential
covariates. The authors demonstrated that periodontitis
was significantly more common in SLE patients than in
controls. However, the prevalence of the SLE patient
with periodontitis was in the same range as for peri­
odontitis patients with type 2 DM.
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Periodontitis has long been considered a potential
risk factor for type 2 DM. Like the diagnosis of DM,
gestational DM (GDM) is defined as glucose intolerance
but is first identified during pregnancy. Over 200 000
pregnant women are diagnosed with GDM each year in
the United States alone, with the prevalence of GDM in
the Asian population being higher than the average rate
worldwide. GDM negatively affects maternal and fetal
health. In addition, GDM represents an increased risk of
developing type II DM after pregnancy. Recent literature
has demonstrated that periodontitis has also increas­
ingly emerged as a potential risk factor for GDM. Liu
et al218 conducted a population-based study examining
the relationship between the development of period­
ontitis during pregnancy and the onset of GDM. Parti­
cipants without periodontitis at 1 to 4 weeks of gestation
were enrolled in the non-periodontitis group. Period­
ontitis patients who agreed or refused to receive peri­
odontal therapy during pregnancy were separately
enrolled in the periodontitis-treated or untreated group.
At 12 to 16 weeks of gestation, gingival crevicular fluid
(GCF) and venous blood were collected to analyze
bacterial species and serum inflammatory mediators. At
24 to 28 weeks of pregnancy, patients with GDM were
identified by oral glucose tolerance tests. Complete data
from 3523 pregnant women was compiled during the
study. An 11.21% incidence of GDM among the un­
treated periodontitis participants was significantly
higher than the 4.79% incidence among the non-peri­
odontitis participants. Significantly, periodontal treat­
ment during gestation reduced the incidence from
11.21% (untreated group) to 7.32%. Based on multiple
logistic regression analyses, it was found that period­
ontitis in early pregnancy was associated with GDM. P.
gingivalis and the serum TNF-alpha and IL-8 levels also
affected the association between untreated periodontitis
and GDM.
Many population-based studies have suggested a
relationship between cardiovascular disease (CVD) and
periodontitis. However, it is controversial whether per­
iodontitis is an independent risk factor for CVD. Some
studies have reported a significant association between
periodontitis and CVD only among those aged <65
years, while others found a stronger association between
periodontitis and atherosclerotic CVD in participants
>65 years of age. A similar confounding finding is an
association between tooth loss and subclinical athero­
sclerosis in men but not women. Addressing these in­
consistencies, Petrenya et al219 examined the
relationship between periodontitis and cardiovascular
risk in a large Norwegian general population, focusing
on never-smokers and the impact of sex and age. This
study included 2623 participants aged 45-74 without
previous myocardial infarction or stroke. Periodontitis
was defined according to the 2017 American Academy
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of Periodontology and the European Federation of
Periodontology classification system. Ordered logistic
regression analysis examined the association between
periodontitis and cardiovascular risk, adjusting for edu­
cation, toothbrushing frequency, body mass index, and
diabetes. Sub-analyses included stratification by sex,
age, and a separate analysis of never-smokers. It was
shown that Periodontitis Grade B/C was associated with
higher cardiovascular risk than no periodontitis/Grade
A. This association was significant in men and women,
all age groups, and never-smokers. However, when the
never-smokers group was stratified by age, the asso­
ciation remained significant only in those aged 65 to 74.
Atherosclerotic CVD is one of the most studied links
between systemic disease and periodontitis. Erectile
dysfunction (ED) is a multifactorial pathology described
in the male population of 24%. About 65% of ED cases
are caused by an organic pathology related to the in­
ability of the vessels of the corpora cavernosa to accu­
mulate blood. Major Adverse Cardiovascular Events
(MACEs) is an acronym used to describe a composite of
cardiovascular clinical outcomes. Nonfatal ischemic
stroke, nonfatal myocardial infarction, and cardiovas­
cular death are common endpoints used as MACEs. As
described earlier, periodontal disease inflammation is an
independent predictor of the risk of MACEs. Mesa
et al220 hypothesized that diagnosing ED and period­
ontitis can be a predictive and additive factor for future
MACEs. Male patients attending a university-based ur­
ology service were enrolled in a prospective study. ED
was diagnosed according to the accepted international
standards, and sociodemographic data and periodontal
clinical parameters were gathered at the baseline ex­
amination. Major adverse cardiovascular events that
occurred before and during the follow-up were regis­
tered. A total of 158 patients were included, with a mean
follow-up of 4.2 years. A greater number of major ad­
verse cardiovascular events occurred in the group that
presented periodontitis and ED. After adjusting by age
and previous cardiovascular disease in the multivariate
analysis, the annual major adverse cardiovascular event
rate was estimated to be 3.7 times higher in this group.
Periodontal disease treatment therapies
A fundamental therapy in the treatment of periodontal
disease is “Initial Preparation” (IP) or “cause-related”
therapy which aims to reduce or eliminate the pathogenic
bacteria by the mechanical removal of the subgingival
biofilm from the root surfaces through subgingival in­
strumentation (SI). Adjunctive to these procedures is sys­
temic antimicrobials which result in additional clinical and
microbiological benefits. A common antimicrobial regimen
is the simultaneous use of amoxicillin and metronidazole.
However, whether a short-term systemic administration (3
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October 2023
days) in periodontitis with rapid progression may provide
similar clinical, microbiological, and immunological bene­
fits as traditional 7-day protocols are unclear. Cosgarea
et al221 studied 50 systemically healthy patients with ag­
gressive periodontitis (AgP; Stage III/IV Grade C period­
ontitis) treated with SI and adjunctive amoxicillin and
metronidazole. The patients were randomly assigned to
test group (n=25) receiving 500 mg antibiotics (AB) 3 times
a day for 3 days, followed by a placebo 3 times a day for 4
days, or a control group receiving (n=25) 500 mg AB 3
times a day for 7 days. Clinical, microbial, and im­
munological parameters were assessed at baseline, 3
months, and 6 months, and patient-related outcomes were
evaluated after 2 weeks. Examining the number of residual
sites with PD >/=6 mm at 6 months, the null hypothesis
was rejected, and the non-inferiority of the 3-day AB
protocol compared with the 7-day AB protocol was de­
monstrated. In addition, comparable clinical improvements
were obtained for all parameters with both antibiotic
protocols with the investigated periodontopathogens and
pro-inflammatory host-derived markers reduced without
differences between the treatments. Considering the po­
tential development of antibiotic resistance and possible
allergic reactions to any antibiotic, this study supports
using a shortened 3-day systemic antibiotics over a 7-day
protocol as adjunctive treatment to IP therapies.
Complete debridement is often a challenge with IP
therapy using scaling and root planing (SRP) in areas
with PD>5 mm. Studies have demonstrated that a
substantial amount of subgingival calculus will remain
upon the root surface. Mechanical access to the depth of
the pocket and complex root anatomy have promoted a
search for effective and possibly less invasive treatment
approaches than hand instrumentation. Acknowledging
these limitations with hand instrumentation SRP alone,
clinicians have considered the adjunctive use of lasers to
SRP to enhance outcomes. The erbium-doped: yttrium-
aluminum-garnet laser (Er:YAG) (J. Morita) generates
minimal heat, rendering it safe and suitable for root
instrumentation. Several in vitro experiments have de­
monstrated this laser’s ability to remove calculus and
cementum thermal damages safely. However, results
from clinical studies showing the superiority of the
Er:YAG in the non-surgical treatment of periodontal
disease are varied. Er:YAG settings for periodontal
treatment usually range from 100 to 180 mJ, with 160 mJ
being the most used energy setting. A lower-level set­
ting, 40 mJ, has been suggested based on in vitro data.
Gurpegui Abud et al222 conducted a RCT comparing the
differences in periodontal clinical outcomes, duration of
the procedure, and patient's experience between con­
ventional scaling and root planing and low level
(Er:YAG) in the treatment of generalized moderate to
severe chronic periodontitis. In a split-mouth fashion,
the right and left sides were randomly allocated into 2
Cagna et al
477
treatment arms: conventional scaling and root planing
versus laser-assisted scaling and root planing. Both
treatments improved overall, but no significant differ­
ences were found between modalities for clinical at­
tachment gain or PD reduction. This study was in
concert with other clinical studies that fail to demon­
strate the clinical superiority of laser therapy compared
with conventional SRP therapies. Despite the lack of
clinical superiority, operator efficiencies and decreased
treatment times are advantages of laser IP therapies.
Simvastatin (SIM) is a specific competitive inhibitor
of 3-hydroxy-2-methylglutaryl coenzyme A reductase
and was initially developed to reduce serum cholesterol.
In addition to its use in treating hyperlipidemia, SIM has
been shown to have anti-inflammatory and bone ana­
bolic properties. Local application of statins has been
shown to reduce periodontal pockets, clinical attach­
ment loss, and inflammation in human clinical trials
during IT. However, it is unknown whether the appli­
cation of SIM results in similar improvements in clinical
outcomes when a patient population is undergoing
periodontal maintenance therapies. Killeen et al223
conducted a RCT examining whether the use of a local
application of SIM in a methylcellulose (MCL) carrier
(SIM/MCL) following SRP and limited papillae reflec­
tion (PR) with endoscopic evaluation is effective in im­
proving CAL. Fifty patients with Stage III, Grade B
periodontitis presenting with a 6 to 9 mm interproximal
PD with a history of BOP were included in the study.
Experimental and control therapies were randomly as­
signed. Root surfaces were accessed via reflection of the
interproximal papillae, followed by SRP assisted with
endoscope evaluation and SIM/MCL or MCL applica­
tion. CAL, PD, BOP, plaque presence, and radiographic
bone height measurements were evaluated at baseline
and 12 months. The results demonstrated that the ad­
dition of SIM/MCL to PR/RP improved CAL, PD, and
BOP compared with PR/RP alone in periodontal main­
tenance patients as well as reducing PD, BOP, and in­
creasing bone height compared with local MCL in
patients on periodontal maintenance therapies. This
study supports further investigation into using SIM
when treating periodontal maintenance patients.
Over the past 2 decades, membranes, biomaterials,
and biologics have been used for the regenerative treat­
ment of periodontal infrabony defects. These biological
agents are now routinely used in periodontal regenera­
tion therapies. The American Academy of Periodontology
Best Evidence Consensus conducted a systematic review
on the use of biological mediators in contemporary clin­
ical practice. This systematic review224 evaluated the effect
of biologic agents, specifically autogenous blood-derived
products (ABPs) (PRF or PRP), enamel matrix derivative
(EMD) (Emdogain), and recombinant human platelet-
derived growth factor-BB (rhPDGF-BB) (Gem21-s), on
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the regenerative outcomes of infrabony defects. A de­
tailed systematic search was conducted to identify eligible
RCTs reporting the results of periodontal regenerative
therapy using biologics to treat infrabony defects. A fre­
quent mixed-modeling approach to network meta-ana­
lysis (NMA), characterized by the assessment of three
individual components for the treatment of an infrabony
defect (application of bone graft material or BG, biological
agent, and barrier membrane), was performed to evaluate
and compare the relative efficacy of the different com­
ponents, on the outcomes of different therapeutic mod­
alities of periodontal regeneration. The quantitative
analysis showed that adding biological agents to bone
grafts significantly improves the clinical and radiographic
outcomes compared with BG and flap procedures alone.
Barrier membranes enhanced the regenerative outcomes
of BG but did not provide further benefits in combination
with biologics. The type of BG (autogenous, allogeneic,
xenogeneic, or alloplastic) and the biologic agent (EMD,
PRF, PRP, or rhPDGF-BB) played a significant role in the
outcomes of infrabony defects. Allogeneic and xeno­
geneic BGs exhibited statistically significantly superior
clinical gain, while rhPDGF-BB and PRF demonstrated
significantly higher stability of the gingival margin and
radiographic bone fill/gain. Overall, rhPDGF-BB showed
the most significant effect size for most parameters, in­
cluding CAL gain, pocket depth reduction, less gingival
recession, and radiographic linear bone gain. In addition,
combination therapies involving BGs+biologics or BGs
+barrier membrane proved superior to monotherapies.
A consequence of increased life expectancies is the
generalized aging of society. With this aging, an increased
number of elderly patients have required periodontal
therapy. This is related to the increased prevalence of
periodontitis with age. However, only limited evidence is
available on the impact of age on the outcomes of peri­
odontal regenerative therapy. Mikami et al225 investigated
the influence of chronological aging on periodontal re­
generative therapy (PRT) outcomes with procedures
using EMD as a biologic. Two hundred fifty-three intra-
bony defects in 151 patients, including 44 with furcation
involvement, were prospectively investigated for 3 years
after regenerative therapy with EMD by evaluating
probing pocket depth (PPD), CAL, and radiographic
bone defect depth (RBD). The influence of age on these
outcomes was assessed using multilevel regression ana­
lyses adjusted for confounders. Significant improvement
was observed with PPD, CAL, and RBD gains at the 1-
and 3-year examinations. At the 1-year examination,
multivariate analysis revealed a significant negative as­
sociation between age and improvement in PPD and
CAL, but these differences were no longer evident at the
3-year examination. Although aging may delay tissue
maturation in the short term, it did not affect the out­
comes of PRT on long-term observation.
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Due to the complex anatomic morphology, furcation
involvement is one of the most difficult challenges when
managing periodontal disease. To enhance regenerative
outcomes in furcation defects, biologics have been
suggested. For example, metformin (MF) (1,1-dimethyl
biguanide), an oral hypoglycemic drug, has shown a
stimulating effect on osteoblast differentiation and bone
formation. Likewise, platelet-rich fibrin (PRF) is useful
in periodontal regeneration procedures by enhancing
the maturation of soft tissue and regeneration of bone
via the cells and the growth factors contained in the
three-dimensional structure of PRF. Swami et al226
conducted a study to evaluate and compare the effects of
1% MF plus PRF over PRF alone in treating Grade II
furcation defects, clinically and radiographically, using
cone beam computed tomography. This split-mouth
clinical trial randomly allotted 21 patients with 42 bi­
lateral Grade II furcation defects into two groups: Group
I was treated with PRF alone, while Group II was treated
with 1% MF gel and PRF. The primary outcome para­
meters were CAL and horizontal probing depth (HPD).
The secondary outcome parameters were PD and defect
volume (DV). The clinical parameters were evaluated at
3, 6, and 12 months and the radiographic parameters at
12 months. Both the study groups showed improve­
ments. However, a more significant mean reduction of
PD, HPD, and CAL gain was observed in the MF group
versus the control group. In addition, a significant re­
duction of DV was exhibited radiographically in the MF
group compared with the control following 12 months.
Another study examining the adjunctive benefits of
PRF barriers in the treatment of furcation defects was
conducted by Serroni et al.227 This study evaluated the
additional benefit of leukocyte and platelet-rich fibrin
(L-PRF) to autogenous bone grafts (ABGs) alone in the
treatment of mandibular molar degree II furcation in­
volvement. Fifty-four patients exhibiting one buccal or
lingual mandibular molar furcation defect were ran­
domly assigned to three treatment groups: Open flap
debridement (OFD)+ABG+L-PRF, OFD+ABG, and
OFD. PD, horizontal clinical attachment level (HCAL),
vertical clinical attachment level (VCAL), gingival re­
cession (GR), and radiographic parameters were eval­
uated at baseline and 6 months after treatment. No
significant differences within each group were reported
for GR changes. Still, statistically significant HCAL,
VCAL, PD, and VBL improvements were observed in all
groups except for VBL in the OFD group. However, at 6
months, the mean HCAL gain in the OFD+ABG+L-PRF
group was significantly greater than in the OFD+ABG
and OFD groups. Additionally, the OFD+ABG+L-PRF
and OFD+ABG therapies produced a significantly
greater clinical and radiographic improvement than
OFD. This study supports the adjunctive use of L-PRF in
treating furcation defects.
Cagna et al
October 2023
As described earlier, the L-PRF barrier is an auto­
logous blood product derived from the patient’s venous
blood. Many factors can affect this barrier's structure and
physical integrity. Ockerman et al228 examined the po­
tential influence of antithrombotic medications on L-PRF
membranes. Tensile tests and cell counts were performed
with L-PRF membranes originating from patients on
anticoagulants and antiplatelet medications versus pa­
tients not taking antithrombotics. The authors demon­
strated that compared with controls, membranes from
anticoagulated donors were physically weaker. The per­
centage of leukocytes was also lower in the anticoagulant
group compared with controls. However, the unknown
method error makes it questionable whether the statis­
tical significance is meaningful. There was no difference
between membranes from the control group and the
group on antiplatelet therapies. These results indicate that
L-PRF membranes originating from patients on antic­
oagulants are physically weaker, stretch less far, and
contain fewer leukocytes than those from patients not
taking these drugs.
For 25 years, less invasive flap designs and clinical
procedures have been developed using papilla pre­
servation flaps, microsurgical instrumentation, and en­
hanced clot stabilization techniques. As a result,
minimally invasive surgical procedures had demon­
strated comparable, if not improved, outcomes to con­
ventional surgical techniques.
One minimally invasive flap design, known as the
minimally invasive surgical technique (MIST), uses small
split-thickness incisions, a single flap approach with
minimal suturing, and preservation of the inter-dental
papilla. This technique aims to preserve the blood
supply to the periodontal tissues and is aided by using a
microscope and a videoscope with a small digital
camera. The minimally invasive non-surgical technique
(MINST) protocol has similar objectives to MIST tech­
niques, with the difference of completely avoiding inci­
sions and suturing altogether, with a consequent
reduction in chair time and potential morbidity.
However, when such flap management techniques are
employed, the additional need and benefit of grafting
materials or biologicals have been questioned.
Anoixiadou et al229 conducted a study comparing the
efficacy of MINST without EMD in treating intrabony
defects ≤7 mm. The control group received MINST,
while the experimental received MINST+EMD. Sig­
nificant improvements were observed in both groups at
12 months, with no differences in mean PD reduction,
CAL gain, and defect resolution for the MINST and the
MINST+EMD groups. This study suggests that choosing
flap management techniques may be as important as
biological modifiers in regenerating intra-bony defects.
Cortellini et al230 also examined the adjunctive role of
biologics when using the modified minimally invasive
Cagna et al
479
surgical technique (M-MIST). While short-term ob­
servations show similar results as with flap alone or
adjunctive regenerative materials, they analyzed the 10-
year outcomes using the M-MIST technique with and
without biologics. Forty-five intrabony defects in 45
patients were randomized to M-MIST alone (N=15),
combined with enamel matrix derivative (M-MIST +
EMD, N=15), or EMD plus bone-mineral-derived xe­
nograft (M-MIST + EMD + BMDX, N=15). Supportive
periodontal care and necessary re-treatment were pro­
vided for 10 years. CAL differences remained similar for
all three groups over 10 years. Four episodes of disease
recurrence occurred in the M-MIST group, four in the
M-MIST + EMD group, and five in the M-
MIST + EMD + BMDX group. No significant differences
in complication-free survival were observed between the
three groups, averaging 7.46 years. When the baseline
cost of treatment was considered, the total cost was
lower for M-MIST alone therapy.
Those above minimally invasive flap techniques en­
hance the primary coverage of the healing site. Post-op­
erative swelling is believed to be a natural healing event
that can negatively impact the ability to maintain primary
closure, with excessive swelling exerting a tensile force on
the incision. Modifications of surgical protocols which
decrease swelling may improve the maintenance of pri­
mary closure. The use of steroids has also been demon­
strated to reduce swelling. Vieth et al231 examined the
effect of the steroid dexamethasone on post-operative
swelling and pain following flap surgery. This rando­
mized, crossover trial sought to determine if a pre­
operative intravenous (IV) dose of dexamethasone reduces
pain, swelling, and analgesic usage following periodontal
surgery. Thirty-seven patients planned for 2 similar peri­
odontal flap surgeries under IV sedation were enrolled.
Patients were randomized to receive either 2 mL (8 mg) of
dexamethasone sodium phosphate or 2 mL of IV solution
(placebo) before the first surgery and 2 mL of the other
solution before the second surgery. Postoperative dis­
comfort was managed with standardized 600 mg ibu­
profen and 325 mg acetaminophen. A smartphone
application was used to record self-assessed pain and
swelling scores. IV dexamethasone was associated with a
significant reduction in pain at 12, 24, 48, and 72 h and
swelling at 12, 24, 48, and 168 h postoperatively compared
with placebo. No significant differences were found in the
number of ibuprofen tablets or acetaminophen between
dexamethasone and placebo surgeries.
Soft tissues adjacent teeth and implants
Soft tissue thickness (STT) has been documented as an
essential anatomical criteria factor in regeneration, per­
iodontal and peri-implant health maintenance, function,
and acceptable esthetics. Current methods to quantify
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480
STT use direct and indirect measurements, including
transgingival bone sounding, intraoperative spring cali­
pers, ultrasound assessment, cone beam computed to­
mography (CBCT), and the standard of histologic biopsy
analysis. CBCT scans producing Digital Imaging and
Communications in Medicine (DICOM) files can be
used to analyze STT non-invasively. However, errors can
occur if the buccal mucosa contacts the area of interest
without retraction. Another digital method for mea­
suring STT is incorporating an intraoral surface scan,
generating an STL file, and registering this STL file with
a DICOM file set. This fully digital approach to quanti­
fying STT is an objective, reproducible, non-invasive,
and precise method to measure STT. Ferry et al232
compared 3 methodologies used to quantify STT: bone
sounding, DICOM data alone, and DICOM and STL
registration to absolute histomorphologic values. Five
human maxillae, including the anterior maxillary teeth,
provided 90 sites for analysis. For standardization, re­
ference grooves were placed at each tooth's cervical
margin and the long axis. Direct measurements with a
25 K-file were completed at the facial soft tissues at 3.00,
5.00, and 7.00 mm from the apical marginal reference.
Indirect measures were performed with an implant
planning software program. Histological measurements
were rendered using an imaging software program. This
study demonstrated that bone-sounding techniques
overestimated STT by 0.22 mm, and DICOM under­
estimated STT by -0.23 mm. Combing DICOM and STL
file registration had a non-statistically significant dif­
ference, -0.04, compared with the histologic standard.
Future studies using STT as a clinical variable or out­
come should use STL file registration with a DICOM
data set to provide the highest accuracy.
Clinical evidence indicates that autogenous sub­
epithelial connective tissue graft (SCTG)-based bila­
minar procedures (such as, SCTG + coronally advanced
flap [CAF]) typically render the best treatment outcomes
in terms of complete root coverage (CRC), mean root
coverage (MRC), keratinized tissue width (KTW) gain,
and long-term stability of treatment outcomes.
Therefore, SCTG-based bilaminar procedures are con­
sidered the standard for treating single and multiple
GRD.233 However, alternative procedures have been
developed using other graft materials such as acellular
dermal matrix grafts (ADMG), xenogeneic porcine col­
lagen matrices (XCM), EMD, and PRF. Chambrone
et al233 conducted a systematic review answering the
question: How do the clinical outcomes of SCTG + CAF
compare with the most frequently reported alternative
root coverage procedures in sites presenting with a
single GRD and with no interproximal tissue loss? A
frequentist network meta-analysis was conducted for
CRC, MRC, and KTW changes. Thirty-eight studies re­
porting on 830 patients and 1265 GRD were included.
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Volume 130 Issue 4
SCTG + CAF was ranked as the most efficient treatment
approach for MRC, CRC, and KTW gain at 6 and 12
months after surgery, except for MRC at the 12-month
follow-up, where enamel matrix derivative plus CAF
exhibited superior results.
As discussed earlier, the adjunctive use of biologics
has been demonstrated to benefit the regeneration of
intrabony defects. Chambrone et al234 conducted a
systematic review examining the efficacy of the biolo­
gics, autologous blood products (ABP) such as PRF,
EMD, and rhPDGF-BB in root coverage and gingival
augmentation therapies. A network meta-analysis
(NMA) was conducted to assess the effect of different
surgical interventions on the primary clinical outcomes
of MRC%, CRC%, KTW, GT change, and recession
depth (RD) reduction. Regarding MRC%, the treatment
modalities EMD+CAF and PRF+CAF failed to show
statistically significant differences compared with CAF
alone (control group), with each other, or superiority to
SCTG+CAF. Treatment with SCTG+CAF also led to a
statistically significantly higher RD reduction. Using
ABPs, EMD, or rhPDGF-BB with a CAF for root cov­
erage is safe and generally promotes significant im­
provements to baseline clinical parameters. However,
the adjunctive use of ABPs and EMD does not sub­
stantially improve clinical outcomes and patient-re­
ported outcome measures compared to those achieved
using CAF alone. Although some studies have reported
equivalent results for rhPDGF-BB+CAF compared with
the standard intervention, the evidence is limited.
Biologics are frequently employed as an adjunct when
allografts or xenografts are used as a substitute for an
autograft. In addition, the treatment of multiple recession
sites often requires the use of non-autogenous tissue due
to a lack of sufficient donor material. Tavelli et al235
evaluated the efficacy of rhPDGF-BB combined with a
cross-linked collagen matrix (CCM) for treating multiple
adjacent gingival recession type 1 defects (MAGRs)
combined with a CAF. Thirty patients were enrolled in
this triple-blind, randomized, placebo-controlled trial and
treated with either CAF+CCM+rhPDGF-BB or CAF
+CCM+saline. The primary outcome was mean root
coverage (mRC) measured at 6 months. At 6 months, the
mRC of the CCM + rhPDGF-BB and CCM alone groups
were 88.25% and 77.72%, respectively. A significant gain
in gingival thickness was consistently observed for both
treatment arms but more significantly for the patients
receiving the matrix containing rhPDGF-BB. The
rhPDGF-BB+CCM-treated patients also presented more
significant volume gain, greater soft tissue thickness, and
a superior esthetic score.
An anatomical site factor that negatively impacts the
outcomes of open flap type root coverage procedures is a
strong labial muscular pull and a shallow vestibular
depth (VD). A shallow VD is frequently associated with
Cagna et al
October 2023
gingival recession defects in mandibular sites. However,
evidence regarding its impact on the outcomes of root
coverage procedures is limited. Blasi et al236 evaluated
the influence of VD on the outcomes of root coverage
therapy consisting of a CAF + CTG. This study selected
patients presenting gingival recession defects (GRD)
with a minimum depth of 2 mm for inclusion. Clinical
examinations were performed, and intraoral scans were
obtained at baseline, 3 and 6 months after surgery to
assess changes in clinical parameters. The VD was de­
termined by applying a standard retraction force from an
Optigate retractor and performing a digital intraoral
scan. A total of 20 patients were enrolled, and 44 teeth
were treated with a CAF+CTG procedure. Recession
depth decreased, and mean gingival thickness increased
in all treated sites. The % root coverage and incidence of
complete root coverage CRC were significantly corre­
lated with the baseline VD. Each additional 1 mm of
baseline VD implied a gain of 6.58% for % root coverage
and increased 2.75 times the probability of achieving
complete root coverage with this gingival augmentation
procedure. It should be noted that this negative effect of
a shallow vestibule has not been demonstrated for
gingival augmentation procedures which use a tun­
neling approach.
Often a gingival recession defect clinically presents
as a combined defect (CD) which is the association
between gingival recession (GR) and a non-carious
cervical lesion (NCCL). Approximately 50% of GR is
believed to present defects on the tooth surface because
of an NCCL. NCCLs are classified into 4 categories
based on the tooth surface topography and the depth of
the NCCL. Class B- defects present with an uni­
dentifiable CEJ without a step in the tooth structure.
Class B+ presents an unidentifiable CEJ with a step or
deeper NCCL, affecting both the root and crown sur­
faces. These classes of CDs are often treated with the
placement of a Class V composite resin restoration and
a gingival augmentation procedure. A CTG+CAF often
yields less than ideal esthetic outcomes in these clinical
situations. Allografts and xenografts in treating CDs
have been suggested as an alternative to autografts.
Mathias-Santamaria et al237 evaluated using collagen
matrix (CM) as adjunctive to a CAF. Sixty-two patients
presenting 62 CDs were randomly allocated evenly to
either the CAF group: partial restoration of the NCCL
and CAF, or to the CAF+CM group: partial restoration
of the NCCL and CAF associated with CM. After 12
months, root coverage and recession reduction were
similar for both groups. However, CAF+CM resulted in
a higher increase in KT width and KT thickness gain.
This study suggests that replacing the missing hard
tissue structure with a composite resin restoration may
decrease the need for an autogenous graft when
treating CD sites.
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While the CTG with a CAF may be considered the
standard for treating recession defects, procedures as­
sociated with lower morbidity are often used. As a result,
more convenient and unlimited supply harvest graft
substitutes, including those that could provide greater
soft tissue volume augmentation, have been pursued.
McGuire et al238 conducted an RCT comparing the use
of volume-stable collagen matrix (VCMX) (Fibroguide)
plus a CAF versus a control group using CTG+CAF.
Thirty patients received control and test therapies; all
were available for follow-up measures. The average
percent root coverage for the CTG+CAF group was
90.5% versus 70.7 for the VCMX+CAF group. Using
VCMX+CAF for root coverage procedures was demon­
strated to be inferior to CTG+CAF but resulted in less
morbidity and was preferred by patients.
The gingival augmentation procedures studies cited in
this review used an open-flap surgical approach. In this
approach, an incision is made across the base of the
papillae, and a flap is elevated. An alternative flap
methodology employs a tunneling approach whereby the
papillary tissue remains contiguous with the buccal or
palatal/lingual flaps. Elmahdi et al239 conducted a study
comparing the use of 2 grafting materials, a subepithelial
connective tissue graft (SCTG) and acellular dermal ma­
trix (ADM) (Puros), with the modified coronally advanced
tunnel technique (MCAT) in the management of multiple
adjacent gingival recessions (MAGRs). Twenty-four pa­
tients with type I MAGR sites were randomly allocated
and treated with ADM+MCAT (test group) or
SCTG+MCAT (control group). After 9 months, significant
reductions in the recession defect increase in gingival
thickness and gains in CAL were seen in both the test
and control groups. In addition, patient satisfaction with
esthetic outcome 9 months after treatment did not differ
between test and control groups.
The recession of the soft tissue margin adjacent to a
dental implant in the esthetic zone is problematic and
often significantly negatively impacts patients' QoL. The
recession of the soft tissue margin around dental im­
plants is estimated to occur in about half of all patients
after 6 months, and an apical shift of the mucosal
margin of 1 mm can be anticipated after the abutment
connection. Tavelli et al240 have proposed the term peri-
implant soft tissue dehiscence (PSTD) to describe this
healing phenomenon and have suggested that PSTD
and gingival recession may have similar risk factors/in­
dicators, including the width of the keratinized mucosa
width (KMW), mucosal thickness (MT), the buccal-lin­
gual positioning of the implant along with the dehis­
cence of buccal bone. Tavelli et al240 conducted a
retrospective analysis of subjects with ≥ 1 healthy dental
implant in the esthetic zone. Clinical and ultrasono­
graphic measurements, including PSTD class and sub­
class, PD, keratinized mucosa width (KMW), mucosal
THE JOURNAL OF PROSTHETIC DENTISTRY
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thickness (MT) at 1 mm and 3 mm, buccal bone distance
(BBD), and buccal bone thickness, were evaluated in
healthy implants and implants with PSTD. The pre­
valence of PSTD was determined to be 54.2%. The most
frequent type of PSTD was characterized by having an
implant-supported crown visually longer than the clin­
ical crown of the homologous tooth, often with the
visible abutment/implant fixture exposed to the oral
cavity. Multivariate analysis showed that the presence of
an adjacent implant, a longer time of the implant in
function, limited MT, reduced KMW, and increased BBD
was significantly associated with PSTD.
Implant-supported interim restorations are often
used to counteract and minimize the changes in the
peri-implant tissues following insertion of the definitive
restoration. Multiple descriptive studies have outlined
methodologies for the fabrication of interim implant-
supported restorations. Most studies describe a concave
emergence profile. Conversely, a convex contour of the
emergence profile is recommended when an implant is
placed in a too-palatal or too-lingual location or the
coronal aspect of the transmucosal zone is near the
marginal mucosa. There is an insufficient number of
studies investigating the effect of the different emer­
gence profiles on clinical and esthetic outcomes.
Siegenthaler et al241 investigated the impact of the
submarginal contour, either convex or concave, of im­
plant-supported crowns upon the mucosal margin sta­
bility up to 12 months after insertion of the final
restoration. Forty-seven patients with a single implant in
the anterior region were randomly allocated to one of
three groups: (1) CONVEX (n=15), implant provisional
and an implant-supported crown both with a convex
profile; (2) CONCAVE (n=16), implant provisional and
an implant-supported crown both with a concave pro­
file; (3) CONTROL (n=16), no provisional (healing
abutment only) and an implant-supported crown. All
patients were recalled at baseline, 6, and 12 months. The
frequency of mucosal recession amounted to 64.3% in
group CONVEX, 14.3% in group CONCAVE, and 31.4%
in group CONTROL. Regression models revealed that a
CONVEX profile was significantly associated with re­
cessions. However, there was no statistical difference in
the pink esthetic scores between the 3 treatment groups,
with the control group displaying equivalent results. As
expected, the CONVEX and CONCAVE groups were
associated with more appointments and costs than the
CONTROL group. Using implant-supported interim
restorations with a CONCAVE emergence profile re­
sulted in greater stability of the mucosal margin com­
pared with a CONVEX profile up to 12 months of
loading. This is accompanied, however, by increased
time and costs compared with the absence of any pro­
visional, which may not necessarily enhance the esthetic
outcomes.
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
During immediate implant placement, the sig­
nificance of the size and shape of the healing abutment
on the preservation of the peri-implant tissue has been
described in the literature. Most of these studies ex­
amined implants located in the esthetic zone, with an
enhanced esthetic outcome being a major goal of
therapy. In the posterior region, maintenance of soft
tissue forms may not be esthetically necessary, but
functionally just as important as in the anterior regions.
Amato et al242 evaluated the role of different healing
abutment designs in compensating for the buccolingual
volumetric tissue change following flapless single-tooth
immediate extraction placement in the molar area. Pa­
tients needing extraction and replacement of a first or
second molar in the mandible or maxilla were con­
secutively recruited for the study. Immediately after ex­
traction and implant placement, 1 of 5 abutment types
was connected, including a Ø5-mm healing abutment
(group 1); a Ø6-mm healing abutment (group 2); a
Ø7.5-mm healing abutment (group 3); a complete
contour interim restoration (group 4); and custom, gin­
gival margin former type healing abutment (group 5).
The buccal-palatal dimension (BPD) was measured on
the diagnostic casts at 1, 3, and 5 mm apical to the free
gingival margin, and horizontal volumetric changes
were compared between baseline and 2, 4, and 6
months. The authors found that the wider the healing
abutment, the greater the amount of soft tissue pre­
served. The gingival margin former type of healing
abutment displayed the best results even in comparison
with the complete contour interim crown.
While the advantage of fabrication of an interim re­
storation for immediate implant placement is becoming
more evident, technical problems exist in the methodol­
ogies used to replicate the exact form of this provisional.
Xiong et al243 conducted a study to quantitatively evaluate
the effect of implant-supported interim restorations
(ISIRs) on the accuracy of the intraoral scanned peri-
implant soft-tissue profile in the esthetic area. Sixteen
patients with a single ISIR in the maxillary central in­
cisor's region were enrolled with 3 recording methods
were sequentially used in each patient: an intraoral
scanning (IOS) with the ISIR, a conventional impression
using the ISIR as impression coping, and a routine IOS
without the ISIR. STL files of the 3 recording methods
obtained from the same patient were superimposed, and
the conventional impression method was used as the
reference model. Dimensional analyses were performed.
The peri-implant mucosa without the ISIR immediately
collapsed (<20 s), particularly on the palatal side of the
labial mucosa and the labial side of the palatine mucosa.
Consequently, the IOS without the ISID led to an overall
dimensional deformation in the cuff-like submucosal re­
gion, significantly more prominent than in the IOS with
the ISIR. The authors suggest that scanning the implant-
Cagna et al
October 2023
supported interim restoration is essential for accurately
replicating the intraorally scanned peri-implant soft-
tissue profile.
Biology of alveolar bone and osteonecrosis of the jaw
Periodontal tissue destruction highly depends on the
host’s susceptibility to bacterial infection. An over-acti­
vated host immune response leads to immune cell in­
filtration, promoting osteoclast differentiation and
activating osteoclastic activity. The destruction of both
soft and hard tissue of the periodontium follows.
Osteoclast differentiation is stimulated by the receptor
activator of NF-κB ligand (RANKL), produced by several
cell types, B cells, T cells, osteoblasts, and osteocytes.
Lee et al previously reported that VnP-16, a motif of
human vitronectin, inhibits IL-1α-induced bone de­
struction by restraining osteoclast differentiation and
promoting osteoblast differentiation and bone formation
while concomitantly impeding osteoclastic bone re­
sorption. This same group conducted a study244 in­
vestigating whether VnP-16 prevents or reverses
alveolar bone resorption induced by ligature-induced
periodontitis in an animal model. Ligature-induced
periodontitis was induced by ligating rodent animals’
bilateral mandibular first molars. VnP-16 was applied
topically into the gingival sulcus via an intra-sulcular
injection or administered directly into the gingiva via
intra-gingival injection. Micro-computed tomography
analysis and histological staining were then performed.
VnP-16 promoted osteogenic differentiation of period­
ontal ligament cells. VnP-16 also modulated the host
immune response by reducing the number of RANKL-
expressing lymphocyte cells by suppressing RANKL and
interleukin (IL)-17A production. Furthermore, local ad­
ministration of VnP-16 significantly prevented and re­
versed alveolar bone loss induced by ligature-induced
periodontitis.
Medication-related osteonecrosis of the jaw
(MRONJ) is a rare but severe adverse event associated
with administering bone antiresorptive agents. The exact
prevalence and factors related to the development of
MRONJ remain controversial in part due to variances in
reporting criteria and sampling methodologies. An ex­
tensive study by Ishimaru et al245 determined the pre­
valence, incidence rate, and risk factors of developing
MRONJ. They used a population-based retrospective
cohort study using the National Database of Health
Insurance, an administrative claims database of all pa­
tients in Japan. The study included patients who newly
began using antiresorptive drugs over a two-and-a-half-
year period. The primary outcome was the development
of MRONJ. They identified 2 819 310 patients who re­
cently used antiresorptive medications during the study
period. Of these patients, 2 664 104 (94.5%) had
Cagna et al
483
osteoporosis, and 155 206 had cancer. Among the pa­
tients with osteoporosis, 1603 (0.06%) developed
MRONJ. Among the patients with cancer, 2274 (1.47%)
developed MRONJ; The occurrence of MRONJ was as­
sociated with poor oral conditions (including tooth ex­
traction), age, male sex, drug type, concomitant drug
use, comorbidities, and type of cancer. While these
prevalence and incidence rates are low, they were higher
than those claimed in previous studies. Poor oral health
conditions were more closely related to the development
of MRONJ than any other factors.
While MRNOJ is often associated with the admin­
istration of bone antiresorptive agents, angiogenesis
inhibitors that block the growth of blood vessels have
also been associated with MRONJ. Aminoshariae et al246
conducted a systematic review examining current bone
antiresorptive and angiogenesis medications for their
potential implications for dental surgeries. The authors
demonstrated that MRONJ risk should be evaluated
using antiresorptive and angiogenesis inhibitors before
invasive dental procedures. Patients who have meta­
static carcinoma or have received parenterally adminis­
tered bisphosphonates and denosumab are at a higher
risk than orally administered bisphosphonates or anti­
angiogenic agents. Dose, duration, adjunctive medica­
tions, or combination of antiresorptive agents also may
increase the risk of MRONJ. Angiogenic inhibitors as
part of a cancer treatment regimen, with or without
antiresorptive medicines, are also considered high risk.
Antiangiogenic agents, bevacizumab, aflibercept, and
tyrosine kinase inhibitors such as sunitinib were im­
plicated most in the development of MRONJ.
Osteoradionecrosis of the jaw (ORNJ) is a serious
event associated with head and neck cancer (HNC)
radiotherapy (RT). Although ORNJ may develop spon­
taneously, it has been associated with dental procedures
in which bone or tissue is manipulated in a previously
irradiated field. Therefore, ORNJ is hypothesized to result
from radiation injury to the bone within the irradiated
field. The biological mechanism of ORNJ is the formation
of aseptic avascular necrosis due to decreased vascularity.
This increases the risk of infection, tooth loss, and pos­
sible jaw fracture. Prevalence estimates for ORNJ range
from 2% to 15%. The reported wide range in prevalence
is likely related to differences in lesion definition. For
example, a recent Cochrane Collaboration Report of 572
patients undergoing RT for HNC cited a 6.1% incidence
of exposed bone but an incidence rate of ORNJ of 3.1%.
Although dental surgical interventions are associated
with post-RT ORNJ, it is unknown whether pre-RT
dental intervention is associated with lower rates of post-
RT ORNJ. Urquhart et al247 performed a systematic re­
view examining whether dental intervention involving
bone or soft-tissue manipulation pre-RT is associated
with lower rates of ORNJ in patients with HNC. The
THE JOURNAL OF PROSTHETIC DENTISTRY
484
authors demonstrated that patients undergoing pre-RT
extractions might have a 55% increased risk of experi­
encing ORNJ, corresponding to a possible increased ha­
zard of developing ORNJ. However, the statistical
certainty of this conclusion was low due to the hetero­
geneity of the selected studies.
For patients who underwent bony reconstruction,
radiotherapy was a significant risk factor for implant
loss, resulting in a significantly lower implant survival.
Despite the risks outlined by Urquhart et al,247 the
placement of oral implants can substantially benefit
the irradiated patient, especially by improving reten­
tion and mastication. This is especially true in patients
who suffer from xerostomia, making the retention and
fitting of conventional removable prostheses difficult.
Schiegnitz et al248 performed a meta-analysis com­
paring implant survival in irradiated bone with non-
irradiated bone. The meta-analysis was performed for
studies with a mean follow-up of at least three and
five years, respectively. This systematic review re­
sulted in a mean overall implant survival of 87.8%
(34% to 100%). The meta-analysis revealed a sig­
nificantly higher implant failure rate in irradiated bone
than in non-irradiated bone. This meta-analysis also
showed that implants placed into irradiated grafted
bone were more likely to fail than those in radiated
native bone. The implication of this analysis suggests
that treating patients receiving radiotherapy of any
form requires precise individual planning and main­
tenance care. A similar systematic review by Pitorro
et al249 supported these same conclusions, citing a
post-radiation implant survival rate ranging from 80%
to 100%. Prosthesis design should include the possible
failure of one or more implants, with the implants
placed in native bone rather than augmented when
possible.
Statins are therapeutic agents used to treat hyperli­
pidemia. In addition to altering serum lipid levels, they
have multifaceted effects, such as promoting bone for­
mation and angiogenesis, with both an anti-in­
flammatory and antibacterial effect. Sanda et al250
conducted an animal model experiment examining the
effects of fluvastatin injections upon the development of
MRONJ. The maxillary first molars of rats administered
zoledronate and dexamethasone for 2 weeks were ex­
tracted. Two weeks after tooth extraction, rats that de­
veloped MRONJ were included. A single injection of
fluvastatin was administered in the vicinity of the
MRONJ site in the rats. A single application of fluvas­
tatin near the site of MRONJ onset showed a tendency
to close the epithelium, reduce necrotic bone, and form
new bone. This study suggests that a single topical ad­
ministration of fluvastatin may be a novel treatment for
MRONJ.
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
Alveolar ridge preservation, alveolar ridge, and sinus
augmentation
Alveolar ridge preservation (ARP) modalities that use
socket grafting prevent about 2 mm of horizontal and
2 mm of vertical bone resorption. There is limited in­
formation on the need for bone augmentation in the
context of delayed implant placement and whether al­
veolar ridge preservation successfully provided enough
bone volume for successful implant placement. Couso-
Queiruga et al251 conducted a retrospective cohort study
evaluating the efficacy of ARP therapy after tooth ex­
traction compared with unassisted socket healing (USH)
in reducing the need for secondary bone augmentation
before or at the time of implant placement. Non-molar
single-tooth extraction sites with or without simulta­
neous ARP therapy were included in this study, with
CBCT scans obtained before and after tooth extraction.
A logistic regression model was used to evaluate the
effect of pre-extraction facial alveolar bone thickness.
Simultaneous bone augmentation was necessary for
60% of the USH and 11.4% of the ARP groups. Logistic
regression revealed that the odds of not needing sec­
ondary bone augmentation were 17.8 times higher in
sites that received ARP therapy. From an economic
perspective, this study provides a cost-effective rationale
for performing ARP for delayed implant therapies in the
esthetic zone.
The use of biologics has been suggested for ARP,
alveolar ridge reconstruction (ARR), implant site devel­
opment (ISD), and maxillary sinus floor augmentation
(MSFA) procedures. Suárez-López del Amo1 et al252
performed a systematic review analyzing the effect of
ABPs, EMD, rhPDGF-BB, and recombinant human bone
morphogenetic protein-2 (rhBMP-2), on the outcomes
of ARP/ARR and ISD therapy. A total of 39 articles were
included and analyzed qualitatively, but due to the high
heterogeneity across studies, quantitative analyses were
not feasible. The authors found that studies examining
ARP procedures revealed that biologics rendered similar
results to conventional protocols. However, histomor­
phometric outcomes were positively influenced by the
application of biologics. ABPs enhanced new bone for­
mation and reduced the likelihood of early wound de­
hiscence. The use of biologics in MSFA interventions did
not translate into superior clinical or radiographic out­
comes. Of the few investigations evaluating patient-re­
ported outcomes, a modest beneficial impact of biologics
on pain and swelling was seen.
When an implant is placed using a delayed protocol
after an ARP procedure, the implant is typically placed
four to six months after the tooth extraction. The main­
tenance of the residual alveolar ridge dimension beyond 6
months after treatment is unknown. Allen et al253 con­
ducted a study comparing the differences in alveolar ridge
Cagna et al
October 2023
dimensional change following ridge preservation be­
tween 4- and 12-month healing time points using CBCT
analyses. Following extraction, ridge preservation was
performed. CBCT scans were made within 72 h following
extraction with a custom resin stent containing a fixed
radiographic marker. At either 4 months or 12 months
after ridge preservation, patients had a second CBCT
made. No significant differences in buccal and lingual
ridge height loss were detected between the ST and LT
groups. Similarly, no significant differences between the
ST and LT groups were detected in ridge width loss.
Therefore, clinicians may feel confident that a delay in
implant placement for up to a year has no significant
negative impact on the height and width of the healed
ridge when ARP procedures are used.
A plethora of ARP techniques exist. Much con­
sideration is given to what material is placed over the
bone graft or blood clot which occupies the socket.
Velasquez et al254 compared the efficacy of a collagen
wound dressing (Helistat) with a xenograft collagen
matrix (Mucograft Seal) in an RCT. Both test and control
sockets were grafted with a xenogeneic bone graft
(BioOss). Graft containment, extraction socket soft
tissue gap closure, gingival contour, and gingival thick­
ness were examined over 16 weeks. Healing was un­
eventful for both groups, and there was no significant
difference between the times required to close the ex­
traction socket soft tissue gap.
While particulate bone grafts are primarily used to fill
the socket in ARP procedures, there has been a growing
trend to combine the bone graft within a collagen matrix
to enhance the graft and clot stability. Casarez-Quintana
et al255 conducted an RCT to evaluate the histological
wound healing and alveolar ridge dimensional changes
following ridge preservation using two different xeno­
graft/collagen matrices. Fifty-four patients with non-
molar teeth requiring extraction and replacement with
dental implants were enrolled. Teeth extractions were
completed with minimal flap reflection. They were
randomized to receive ridge preservation with either
90% bovine-derived xenograft granules in a 10% porcine
collagen matrix (BioOss Collagen) or a sponge-like
matrix of 80% microparticulate hydroxyapatite allo­
plastic graft with 20% sugar cross-linked porcine type 1
collagen (Ossix Bone). After 16 weeks of healing and at
the time of implant placement, a bone core biopsy was
harvested, followed by dental implant placement. Ossix
Bone presented a statistically significantly higher per­
centage of vital bone than BioOss Collagen. No statis­
tically significant difference was observed for changes in
alveolar ridge dimensions. Ridge dimension changes
were similar between the two groups and were adequate
for implant placement.
Dentin is a mineralized connective tissue whose
composition is nearly identical to bone. The non-
Cagna et al
485
collagenous proteins in dentin are osteopontin, osteo­
calcin, and dentin matrix protein. These proteins can
trigger bone resorption and are involved in bone calci­
fication. Dentin can serve as a functional bone graft for
augmentation if available. Elraee et al256 compared using
a dentin block harvested from impacted wisdom teeth
with an autogenous ramus bone block for horizontal
alveolar ridge augmentation in an RCT of 42 patients.
Dental implants were placed six months after the aug­
mentation, and a core biopsy was performed. All sites
healed uneventfully, and the mean overall crestal ridge
width 6 months after augmentation was significantly
larger with the dentin than with the alveolar block
grafts. The histomorphometric analysis of the bone area
fractions was similar.
In addition to the normal barrier effect, sugar-cross-
linked collagen membranes have been shown to have a
unique capacity for ossification within the membrane.
Therefore, it has been suggested that a scaffold made of
this material (Ossix Volumax) will result in significant
bone augmentation without needing a concomitant bone
graft. Dowlatshahi et al257 examined osseous changes
following lateral bone augmentation using Ossix Vo­
lumax alone and compared it to the combination therapy
using a freeze-dried bone allograft (FDBA) and a re­
sorbable collagen membrane (Bio-Guide) (FDBA/CM).
Thirty patients completed this 9-month prospective two-
center cohort clinical trial. Before surgery and at 9-
months re-entry, linear measurements were performed,
impressions made, and CBCT scans acquired. The FDBA/
CM group yielded better, albeit moderate, increases in
the volume of the edentulous ridge, while OV scaffolds
failed to produce similar results.
Titanium mesh has been used as a physical construct
to contain particulate grafts for many years. While Ti-
mesh does not have cell-exclusive properties, enhanced
space maintenance and stabilization of the blood clot
and graft revascularization support its effectiveness.
Levine et al258 performed a retrospective case series,
examining the implant site development using Ti-mesh
in the maxilla. Fifty-eight mesh procedures combined
with several bone grafts were performed in 48 patients.
Ti-mesh-guided bone regeneration procedures were
performed 2 to 3 months after teeth extraction, and the
implants were placed 6 to 8 months post-augmentation.
The mean horizontal gain after Ti-mesh procedures was
2 mm. Since this study did not use standardized meth­
odologies, comparisons of outcomes of different grafting
materials or biologics can be made. First, however, the
prevalence of complications can be evaluated. Ti-mesh
exposure occurred 22% of the time, with middle-aged
and older adults having significantly higher chances of
mesh exposure than young adults. This reported com­
plication and exposure rate is higher than the 7% pre­
valence described for resorbable barriers.
THE JOURNAL OF PROSTHETIC DENTISTRY
486
Several recent studies explored transcrestal sinus
augmentation in sites with residual bone height ≤5 mm.
A transcrestal approach is minimally invasive with good
to excellent implant survival rates. In addition, clinical
and histologic studies showed that the transcrestal
technique is more predictable regarding new bone for­
mation in narrow compared to wide sinuses, irrespective
of crestal bone height. However, limited information is
currently available on the variables which may influence
intraoperative complications and early implant failure
after sinus floor elevation with minimal residual bone
height using a transcrestal approach. Stacchi et al259
conducted a retrospective multicenter study of patients
who underwent transcrestal sinus floor elevation. The
influence of different factors related to the sinus
anatomy and surgical technique on the incidence of
intraoperative complications and early implant failure
rate after transcrestal sinus lift were investigated. A total
of 430 patients treated with transcrestal sinus floor ele­
vation for single-implant insertion in sites with RBH
≤5 mm were included in the final analysis. Early implant
failure was recorded in 12 patients (2.8%) and was sig­
nificantly associated with the presence of large sinus
cavities and with the occurrence of membrane perfora­
tion. A strong direct correlation was also demonstrated
between sinus membrane perforation and buccal-palatal
sinus width.
Extensive angiogenesis and graft colonization by os­
teoprogenitor cells is an essential biological step for new
bone formation after maxillary sinus floor elevation. It is
logical to assume that the greater the distance from the
source of the native bone, the longer it will take for a
grafted sinus to mature. However, little information exists
about the healing potential of sites with different buccal-
lingual widths within the same maxillary sinus. Stachhi
et al260 studied the histomorphometric outcomes of lat­
eral maxillary sinus augmentations in other areas of the
same cavity and correlated results to buccal-palatal sinus
width (SW) and residual bone height (RBH). Patients
needing maxillary sinus floor elevation (RBH <5 mm) to
insert 2 nonadjacent implants were treated with lateral
augmentation by using a composite graft. Six months
later, 2 bone-core biopsies (mesial and distal) were re­
trieved in implant insertion sites. SW and RBH were
measured with cone beam computed tomography, and
multivariate linear regression analysis evaluated correla­
tions between histomorphometric and anatomical para­
meters. The mean newly formed mineralized tissue
percentage (%NFMT) after 6 months in the mesial and
distal sites was 17.5% and 11.6%, respectively. Multi­
variate linear regression showed a strong negative cor­
relation between SW and %NFMT. Clinicians should
regard sinus width as a guide for graft selection material
and the influence of the healing period.
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
Peri-implant disease and treatment
The interproximal contact loss between a fixed implant
restoration and an adjacent natural tooth has been well
documented. Unlike implants, natural teeth show a
physiologic migration, including tooth eruption, move­
ment within the socket, and the ability to adapt to
functional demands. As the patient ages, there is a
tendency for the natural dentition to move toward the
midline. If an implant restoration is placed distal to the
natural dentition, an opening of the proximal contact is
possible. Likewise, a tooth may also migrate in a distal
direction, away from the adjacent implant restoration, if
an implant is placed to the mesial of the natural denti­
tion. Gasser et al261 studied the quantity of interproximal
contact loss (ICL) between implant restorations and
adjacent teeth after at least 10 years of follow-up. Thirty-
nine patients with 80 implants were re-examined at least
10 years after insertion of final restorations, including
single crowns or fixed partial dentures. Interproximal
contact loss for at least one contact point after 10 years
was observed in 50% of all implants, with mesial contact
points significantly more prone to ICL than distal ones.
The type of restoration had a significant effect on ICL,
with FDPs of 2 implants being significantly more prone
to mesial ICL than single crowns. ICL was also asso­
ciated with a significant increase in PDs but not MBL or
BOP. It can be inferred that while ICL may lead to in­
creased PDs, the prevalence of peri-implant bone loss is
low. This data also suggests that prosthetic design
choices should favor the potential for adding to the
proximal contact should it be lost.
The retention of implant prostheses for rehabilitating
edentulism was initially abutment-level screw-based,
using the installation of a multi-unit (MU) abutment.
The placement of this MU was part of this original
surgical implant protocol. However, these early MU
prostheses had limitations, such as losing retention with
compromised esthetics and occlusion due to the screw
access holes. In addition, early MU abutments required a
3 mm vertical height, impinging upon the available
prosthetic space. In response to these limitations, the
late 1980 s saw the development of implant-level (IL)
connections using a flat-to-flat connection as an alter­
native to the MU screw-retained design. Toia et al262
conducted an RCT comparing the MBL 3-year outcomes
of marginal bone levels, attachment level changes, and
bleeding upon probing between an MU and IL con­
nection for implants with an internal conical connection
(ICC). Fifty patients with 119 implants were randomly
allocated to the MU or IL group. The MBL change was
not significantly different between the groups at any
point. In addition, BOP was increased with the IL group
for the first two years but not different in year three. This
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October 2023
study demonstrates that either connection is considered
a valid alternative when restoring ICC-type implants.
In the esthetic zone, using zirconia abutments has
gained widespread popularity. The biological benefits of
zirconia as an abutment material remain debatable. While
various abutment materials may demonstrate effects on
peri-implant inflammation, histological analysis of biop­
sies from patients with zirconia and titanium abutments
revealed no distinct differences. The perceived differences
in the appearance of soft tissue overlaying these abut­
ments could be due to optical properties rather than
biological differences. Unfortunately, there is a paucity of
RCTs comparing the clinical outcomes using titanium to
zirconia-based abutments. Hosseini et al263 performed an
RCT comparing the biological, technical, esthetic, and
patient-reported outcomes of single-tooth implant-sup­
ported ceramic versus metal-ceramic restorations. The
prosthodontic treatment on single-tooth implants was
randomly assigned to ceramic crowns on zirconia abut­
ments or metal-ceramic crowns on metal abutments. All
patients were recalled to clinical examinations at baseline,
1, 3, and 5. The MBL after 5 years was minor and not
significantly different. The success rate of the implants
based on MBL was 77.4% for the ceramic and 93.7% for
the metal-ceramic restorations. The marginal adaptation
was significantly better for metal-ceramic than for
ceramic restorations. Of interest is that the esthetic out­
comes and patient-reported outcomes between ceramic
and metal-ceramic restorations were not significantly
different in this study.
Titanium is the predominant material of modern
dental implants. Titanium has very good corrosive re­
sistance, partly due to the surface titanium oxide layer.
However, this layer may dissolve in an acidic environ­
ment, allowing the leakage of titanium particles (TP).
Authors have suggested that TPs induce an inflammatory
reaction in the mucosal tissues, although the exact me­
chanism of interaction is controversial. A TP-induced
foreign body reaction has been suggested as a possible
mechanism. Rakic et al264 conducted a case series study
examining titanium particles (TPs) in biopsy specimens
harvested from peri-implantitis lesions to study the his­
topathological characteristics in these peri-implantitis
sites compared to periodontitis sites in the same patient.
Biopsies containing granulation tissue were harvested
during routine surgical treatment in 39 peri-implantitis
cases and 35 periodontitis controls. Intermediate implant
biopsy sections and periodontitis specimens were pro­
cessed for descriptive histological study using hematox­
ylin-eosin staining and for immunohistochemical
analysis. TPs were identified in all peri-implantitis spe­
cimens as free metal bodies interspersed within granu­
lation tissue. However, the presence of macrophages or
multinucleated giant cells engulfing the TPs was not
identified in any specimen as expected in a foreign body
Cagna et al
487
reaction. Peri-implantitis granulations were characterized
by a chronic inflammatory infiltrate rich in neutrophils.
Compared to periodontitis, peri-implantitis tissues
showed higher proportions of macrophages and more
intense neovascularization. Although TPs were identified
in all peri-implantitis specimens, there was no evidence
of any foreign body reaction related to the direct patho­
logical effects of TPs.
While studies have shown that non-surgical treat­
ment is effective for peri-implant mucositis, non-surgical
therapy alone is ineffective in treating peri-implantitis in
most cases. However, published case series studies have
shown promising additional benefits when using sys­
temic antibiotics as an adjunct to non-surgical therapy.
Blanco et al265 conducted an RCT examining the clinical,
radiographic, and microbiological outcomes after non-
surgical treatment of peri-implantitis with or without
adjunctive systemic metronidazole. Implants received a
mechanical non-surgical debridement session and sys­
temic metronidazole or placebo. After 12 months, the
test treatment resulted in significantly greater PD re­
duction and CAL gain compared with the placebo. The
test treatment also resulted in an additional radiographic
bone gain. Clinical success criteria were defined as re­
sidual PD of ≤5 mm with no BOP. At the end of the
follow-up period, 56.3% of patients met the success
criteria in the test group and 25% in the control group.
Peri-implant mucositis can be treated by non-sur­
gical biofilm disruption, while peri-implantitis requires
surgical open-flap access procedures. Non-surgical
procedures can be classified as chemical, physical, or
laser procedures. Airborne-particle abrasive (APA) sys­
tems seem superior to mechanical therapies such as
curettes, ultrasonic scalers, gauze, and rubber cup pol­
ishing. Therefore, Francis et al266 conducted a systematic
review to evaluate in vitro investigations that assess
different treatment modalities to decontaminate tita­
nium surfaces, focusing on the most effective cleaning
procedures. This systematic review demonstrated me­
chanical decontamination proving better results than
laser and chemical procedures, with APA showing the
best cleaning effectiveness. Comparing the chemical
methods, chlorhexidine demonstrated comparable re­
sults with all tested.
Recognizing that nonsurgical therapies alone are in­
sufficient for treating peri-implantitis, it has been ac­
knowledged that surgical intervention is needed to
provide access to the implant surfaces and the peri-im­
plant defect. Unfortunately, studies examining surgical
access therapy alone have failed to provide satisfactory
results predictably. Even with complete disease resolution
after flap access treatment, the previously affected im­
plant often lacks some of its original supporting bone. As
a result, more reports have described reconstructive
therapies for peri-implantitis to regain the lost peri-
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488
implant supporting bone and achieve disease resolution.
Wen et al267 conducted a prospective clinical study as­
sessing the reconstructive potential of a submerged
healing approach for treating intrabony peri-implantitis
defects. Patients with a diagnosis of peri-implantitis were
recruited. Implant superstructures were removed before
the surgical treatment. Surgical treatment included im­
plant surface and defect detoxification using im­
plantoplasty, air-power-driven devices, and locally
delivered antibiotics. The augmentation procedure in­
cluded a composite bone graft and a non-resorbable
membrane followed by primary wound coverage. Sub­
merged healing occurred over the next 8 months. A sig­
nificant clinical bone gain of 3.22 mm was observed at the
re-exposure of the implants. The radiographic analysis
also showed an average gain of 3.47 mm. Three months
after placing new crowns, final PD measures revealed a
significant reduction compared to initial examinations.
This study demonstrates that effective regeneration of the
peri-implant bone defect requires the removal of the
implant prosthesis and the creation of a submerged
healing environment.
DENTAL MATERIALS AND THERAPEUTICS
The 2022 literature on dental materials and therapeutics
continues to reflect the impact of COVID-19 on the
overall dental research community. The number of ori­
ginal study publications continues to lag with a much
greater proliferation of reviews of prior research.
Unfortunately, this trend is evidence that the research
community is slow to restore its lost capacity.
Silver diamine fluoride
The efficacy of silver diamine fluoride (SDF) was re­
ported in several different clinical applications. One
short-term study compared the 9-month survival of
atraumatic restorative treatment (ART) restorations
placed both with and without lesion pretreatment with
38% SDF.268 The restorations were placed in a school
setting on 190 children aged 6 to 12 years using a par­
allel-group design. At 9 months, the restorations placed
with SDF showed a marginal improvement of success
with 58.9% intact restorations over ART alone with
47.8% intact restorations. Two slightly longer clinical
studies explored efficacy via caries arrest. The first
compared 38% SDF to a 5% sodium fluoride (NaF)
varnish on caries in primary teeth of 290 children aged 1
to 3 years.269 This comparative cohort study used
semiannual application of SDF and followed the teeth
for caries arrest or progression over 18 months. Results
showed comparable effectiveness between both treat­
ments with SDF demonstrating 59.1% arrest rate and
fluoride varnish at 58.8% arrested lesions. A systematic
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Volume 130 Issue 4
review was also published that evaluated the caries-ar­
resting efficacy in primary molars.270 A total of 792 pa­
pers were identified with 9 selected for review and 5 of
those for meta-analysis. A high degree of variability
regarding the protocols used for SDF were noted among
the studies. The meta-analysis showed that 622 of 1205
total lesions treated with SDF were arrested and that
biannual applications appeared to be more effective.
Two papers reported on the use of SDF as a vital pulp
capping or indirect pulp capping material. The first was a
RCT that compared a dilute solution of SDF (3.8%) to
light polymerize calcium hydroxide as direct pulp capping
agents in primary molars.271 Fifty-six primary molars
were randomly allocated to either 3.8% SDF or calcium
hydroxide, followed by glass ionomer and a stainless-
steel crown. At 12-month recall, clinical and radiographic
indicators showed similar success rates of 96% for SDF
and 91.6% for calcium hydroxide. Unfortunately, no ne­
gative control was present to evaluate comparable success
without pulp capping. A second systematic review looked
at studies where SDF was used over vital pulps and in­
cluded in vitro, animal, human clinical, and case re­
ports.272 Of 1433 publications, only 5 met the inclusion
criteria and reported on a total of 30 teeth where SDF was
either directly or indirectly applied to vital pulps. Results
showed that direct application of SDF to vital pulp tissues
resulted in complete pulp necrosis. Indirect application to
vital pulps resulted in a mild inflammatory response,
increased odontoblastic activity and an increase in tertiary
dentin formation. This pulpal response is like that ob­
served with calcium hydroxide.
A systematic review looked at the evidence for dif­
ferent professionally applied fluorides to prevent and
arrest dental caries in older adults.273 Of 527 studies
identified, 7 were included in the final review with five
of those rated as having low risk of bias. The root caries
preventive fraction for SDF varied from 25% to 71%, for
5% NaF, the preventive fraction was 64%, and for 1.23%
acidulated phosphate fluoride (APF) gel was 32%. It was
also noted that while 5% NaF varnish and APF gel
prevented root caries, 38% SDF both prevented and
arrested caries in older adults.
Three papers evaluated changes in the OHRQoL
related to SDF treatments. The first reported on changes
in parental satisfaction and children’s OHRQoL after
ART restorations placed both with and without prior
SDF treatment.274 A total of 194 children participated
with approximately half receiving SDF and half a tonic
water placebo on caries 10 weeks prior to receiving ART
restorations. After a 24-month follow-up, there was a
significant improvement in parental satisfaction scores
with their children’s dental health status when lesions
were given the prior SDF treatment, but no statistical
change was detected in the children’s OHRQoL. The
second study evaluated changes in OHRQoL relative to
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October 2023
SDF treatment, a standard package of glass ionomer
sealants and ART in 160 children aged 5 to 13 years.275
The baseline OHRQoL assessment was done with un­
treated decay present and follow-up assessments were
administered after each of the 3 treatment options.
OHRQoL improved over baseline for all 3 treatment
options and there was no difference between SDF and
sealants or ART. One interesting note was that the
changes in OHRQoL were not dependent upon the
severity of baseline decay. A systematic review did a
similar comparison of OHRQoL across SDF versus other
standard therapies.276 After screening. 10 studies were
evaluated, and 5 retained for meta-analysis. Results in­
dicated no differences in OHRQoL between SDF and
ART (d=0.02, 95% CI: -0.32 to 0.36) or a placebo
(d=0.03, 95% CI: -0.16 to 0.22). These results confirm
that there is no discernible impact on OHRQoL across
various non-surgical treatments for dental caries, and
concerns regarding staining by SDF do not seem to af­
fect OHRQoL.
The literature has continued to affirm the efficacy of
SDF as both caries preventive and disease-arresting
therapy. This past year we are starting to see positive
results in patient-reported outcomes added in the form
of quality-of-life measures, and hopefully, research will
continue to expand in the future to address cost-effec­
tiveness and methods to reduce treatment disparities.
Sealants
The efficacy of sealants in permanent molars has been
well established in the literature, but questions remain
regarding how effective sealants are in preventing caries
in primary molars. Two literature reviews and one
clinical trial attempted to address this question. The
clinical trial was a two-arm, parallel-group, tooth-ran­
domized comparison of survival rates between sealing
and restoring deep cavitated lesions on primary mo­
lars.277 A total of 68 molars with ICDAS-5 class lesions
were randomly allocated to surface sealing using a resin-
improved glass ionomer without any caries removal, or
selective caries removal and complete restoration with
the same resin-modified glass ionomer. Teeth were
followed clinically and radiographically for up to two
years. After two years, the success rates were 76% in the
complete restoration group and 48% in the sealing-only
group, however, the survival curves were statistically
significantly different only after two years (P<.001). It
was also noted that no radiographic progression was
observed in either method at any time point. These re­
sults indicate that sealing caries with resin-improved
glass ionomer can be effective at arresting disease, but
these sealants over large occlusal lesions on primary
molars lack the structural integrity observed in more
significant restorations of the same material.
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489
One review of the effectiveness of pit and fissure
sealants on primary teeth compared sealants to no
sealants or to a different sealant in preventing occlusal
caries on primary molars.278 Parallel-group and split-
mouth RCTs were included and studies using complex
interventions such as ART or sealing of cavitated lesions
were excluded. Nine studies were included with 1120
children ranging in age from 18 months to 8 years. Many
studies were limited to comparing two different types of
sealants and made data pooling around the primary
outcome impossible, while only three evaluated the
primary outcome of sealant versus no sealant. Results at
24 months indicated insufficient evidence in preventing
new lesions for fluoride-releasing sealants versus no
treatment (OR=0.76, 95% CI: 0.41-1.42). Glass ionomer
sealants provided mixed results with one study showing
insufficient evidence for a difference from no treatment
after 12-30 months (OR=0.97, 95% CI: 0.63-1.49), and a
second supporting a large beneficial effect of sealants
(OR=0.03, 95% CI: 0.01-0.15). The authors pointed out
considerable shortcomings in the referenced studies
making the certainty of the evidence low or very low,
regardless of the outcome. A second similar review
noted that heterogeneity and inability to pool the data
were significant shortcomings, but they did note that all
nine of the included studies exhibited a direction of ef­
fect favoring sealant use.279 Unfortunately, these papers
indicate that much needs to be done before we have a
more solid evidence base for supporting the use of
sealants on primary molars.
Several papers covered different technical aspects of
sealant application. Two compared self-etch adhesive
systems to conventional acid etching and came to op­
posing conclusions. One paper used a split-mouth ran­
domized design, but with only 35 children and 70
permanent molar teeth, was not adequately powered to
demonstrate a statistical difference in retention and
margin integrity.280 The second trial used a similar design
with 47 children and was able to show that conventional
acid etching was significantly superior to self-etching
sealants in retention (62.1% versus 25.8%, P<.05).
However, there was no difference in caries incidence after
24 months.281 Another technique paper compared re­
tention and caries incidence between a conventional resin
sealant (Helioseal F; Ivoclar AG) and a flowable compo­
site resin (Tetrick Evo Flow; Ivoclar AG) after 36
months.282 A total of 220 caries-free first permanent
molars were randomly allocated to the 2 materials and
after 36 months flowable composite resin showed com­
plete retention in 80.2% of teeth while the sealant had a
similar retention of 85.4%. No differences were found in
either retention or caries incidence indicating that the
flowable was as effective as the resin-based sealant. A
systematic review comparing filled to unfilled resin-based
sealants screened 26 studies and came to a similar
THE JOURNAL OF PROSTHETIC DENTISTRY
490
conclusion that both materials provided similar retention
and protection from caries development.283
A bis-GMA-free pit and fissure sealant (Helioseal F
Plus; Ivoclar AG) was compared with a conventional
control sealant (Helioseal F; Ivoclar AG) in a 2-year
split-mouth RCT.284 First permanent molars on 92
adolescents were evaluated for retention and found to
be similar at 85.9% for the bis-GMA-free material and
86.5% for the conventional bis-GMA-containing sea­
lant. This trial was one of the few to report adverse
events, with none found during the application or at any
of the recall visits. Another material comparison eval­
uated the use of either a giomer sealant (BeautiSealant;
Shofu) or a resin sealant (Conceal F; SDI) applied to first
permanent molars affected by molar-incisor hypomi­
neralization (MIH).285 A split-mouth trial with 39 chil­
dren aged 6 to 9 exhibiting MIH were sealed using the 2
materials and evaluated using the United States Public
Health Service (USPHS) criteria over 12 months. Re­
tention rates were 68% for the conventional sealant, but
only 8% for the giomer at 12 months. The average
survival time was only 4.02 ±4.43 months for the giomer.
The authors speculated that the weaker etching ability of
the giomer resulted in poor performance on MIH-af­
fected teeth.
Sealants remain one of the most effective preventive
therapies available, but the clinical evidence continues to
suffer from variations in study design, controls, study
power, and heterogeneity. The void in reporting adverse
events is also evident in this literature, much as it is with
studies of other dental materials.
Resin-based Composites
One RCT compared computer-aided manufactured in­
direct composite resin restorations (Grandio Blocs;
VOCO) with direct composite resin restorations
(GrandioSO; VOCO) created using a light-polymerized
layering technique.286 After 2 years, 46 restorations were
evaluated, finding no significant differences in most of
the parameters analyzed. The direct technique provided
a slightly better color match, but success rates con­
sidering all properties were 93.3% for the direct re­
storations and 90% for the indirect restorations. A
systematic review was also published evaluating the
performance of resin versus ceramic inlays, onlays, and
overlays.287 The accepted studies required RCTs with
less than a 50% dropout rate and a follow-up of more
than 5 years. Out of 1718 articles 21 were selected for
review meta-analysis. Estimated survival rates at 5 years
were 86% for direct composite resin, 90% for felspathic
porcelain, and 92% for glass-ceramics. At 10 years,
felspathic porcelain (91%) and glass-ceramic (89%)
survived at similar rates, while resin survival dropped to
75%. Failures in all restorations were mostly due to
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Volume 130 Issue 4
fractures (6.2%), endodontic treatment (3%), caries
(1.7%), and debonding (0.9%). A similar systematic re­
view compared resin-matrix CAD-CAM partial coverage
restorations to similar ceramic restorations.288 Seven
studies were included, 6 being RCTs with 1 longitudinal
observational study. CAD-CAM resin-based composite
success ranged from 85.7% to 100%, while the success
rate for ceramic restorations was similar, ranging from
93.3% to 100%. Fracture and debonding were reported
to be the most frequent failure modes for both restora­
tion types.
Bulk-fill composite resins continued to generate a
large amount of interest in 2022, with several papers
devoted to their evaluation. The first was a 3-year split-
mouth trial comparing a bulk-fill system (Filtek Bulk Fill
Posterior; 3M) with a nanohybrid control (Filtek Supreme
XTE; 3M) in 120 direct restorations.289 Survival and clin­
ical quality were evaluated after 3 years of service using
modified World Dental Federation (FDI) criteria. The
mean annual failure rate for the bulk-fill composite resin
was 2.4%, comparable to the nanohybrid composite resin
at 1.8%. No differences could be determined between
materials for any of the assessed parameters. A second
randomized split-mouth trial was a 4-year evaluation of 3
different composite resin systems, a conventional micro­
hybrid (Amelogen Plus; Ultradent Products, Inc), a
flowable bulk-fill nanoparticulate composite resin (Filtek
Bulk Fill Flow; 3M), and a flowable bulk-fill microhybrid
system (SDR; Dentsply Sirona).290 Both clinical perfor­
mance and maintenance of interproximal contacts were
evaluated in 106 restorations. All 3 systems resulted in
decreased proximal contact after 4 years, but all were
rated as satisfactory in clinical performance. The largest
deficiency cited was marginal discoloration, which tended
to be higher with bulk-fill systems. The third paper
compared a bulk-fill (Tetric EvoCeram Bulk Fill; Safco) to
a nanofill composite (Filtek Ultimate; 3M) in a split-
mouth trial in 50 adult patients.291 After 6 years of service,
66 restorations were evaluated, but in this trial, the bulk-
fill restorations performed better in marginal discolora­
tion. The performance in all other clinical parameters was
not significantly different across systems. In a slightly
different twist, another paper compared the 3-year per­
formance of 2 different types of bulk-fill composite resin,
an experimental self-adhesive bulk-fill (SABF; 3M) and a
conventional bulk-fill composite resin (Filtek One; 3M) in
a split-mouth study in 30 patients.292 Success rates were
96.6% for both materials and only esthetic parameters
like marginal staining and adaptation showed significant
deterioration over the 3 years.
Two systematic reviews reported on the comparison
of composite resin restorations placed using either a
bulk-fill method or incremental placement. The first
selected 14 RCTs and found that neither method pro­
vided superior results over multiple criteria on posterior
Cagna et al
October 2023
restorations.293 The second review also included 14
studies and came to the same conclusion, that the
clinical performance of class I and class II composite
resin restorations in posterior teeth is similar regardless
of placement using a bulk or incremental technique.294
One of the longer trials on composite resins was a
report on the 8-year comparison of a flowable composite
resin (Clearfil Flow; Kuraray) with a conventional
(Clearfil AP-X; Kuraray) in 90 non-carious cervical le­
sions in 19 patients.295 After 8 years of service, the
overall survival rate for the conventional composite re­
storations was 98% compared with 82% for the flow­
able. This difference was not statistically significant.
Margin staining increased over time for both materials,
but the wear was only observed in the flowable com­
posite resin restorations.
Another unique study evaluated the effect of pre­
heating resin composite resins during placement.296 A
split-mouth study on 35 patients compared a nanofilled
resin (Filtek Z350; 3M) placed in class I restorations
using either a preheating technique or nonheated. After
36 months, 66 restorations were evaluated using FDI
parameters, and only staining was detected as increasing
significantly in the nonheated restorations. Both
methods of placement were reported as resulting in
clinically acceptable restorations over the 36 months.
Lastly, an updated systematic review and meta-analysis
reported on the efficacy of resin-based direct posterior
restorations and glass ionomer restorations.297 A total of 62
studies met the inclusion criteria, with only 1 considered at
low risk for bias, 42 with an unclear risk of bias, and 19 at a
high risk for bias. Materials were separated by filler type
(microhybrid, nanohybrid, hybrid) as well as bulk-fill,
compomers, and glass ionomers. After 10 years, the sur­
vival rate for composite resin dropped to about 85%
to 90%, with no differences noted between filler types. The
main reasons for failure were bulk fractures and wear
(70%) followed by caries at the margins (20%). For com­
pomers and glass ionomers, the overall survival rate was
about 80% at 6 years, with loss of anatomic contour, loss of
contacts, and retention loss being the leading causes of
failure for glass ionomers and fractures being the primary
mode of failure for compomers.
Overall, the literature continues to show that the
clinical success of resin composites is less dependent
upon composition or technique, that most available
materials can produce clinically acceptable and service­
able restorations, and that the skill and knowledge of
the individual practitioners is the most reliable predictor
of success.
Glass ionomers
A systematic review and meta-analysis reported on the
effectiveness of glass ionomer restorations in preventing
Cagna et al
491
new caries in primary and permanent dentitions as
compared to other types of restorations.298 RCTs were
reviewed to evaluate caries experience increment or caries
incidence in patients with conventional and resin-mod­
ified glass ionomer restorations as well as amalgam and
resin composite restorations. Ten studies were included, 5
of which were selected for meta-analysis. Patients with
glass ionomer restorations of both kinds experienced
lower caries incidence than patients with amalgam or
composite resin restorations (RR=0.67, 95% CI: 0.55-0.82,
P<.001). Conventional glass ionomer restorations de­
monstrated lower caries incidence compared with
amalgam and resin-modified glass ionomer in primary
teeth (RR=0.70, 95% CI: 0.56-0.87, P=.002). Patients with
resin-modified glass ionomer restorations, however,
showed no improvement of caries incidence over com­
posite restorations in both primary and permanent den­
titions (RR=0.83, 95% CI: 0.56-1.22, P=.33).
Two systematic reviews looked at the effectiveness of
glass ionomers in managing caries in patients undergoing
head and neck radiation treatment. The first review in­
cluded 4 articles and noted that glass ionomer cement
restorations presented higher marginal adaptation fail­
ures than resin-modified glass ionomer and composite
resins.299 Secondary caries were absent in patients with
conventional glass ionomer restorations at all follow-up
periods, but the evidence was not sufficient to conclude
that they are more effective than other materials at pre­
venting radiation-related caries. The second systematic
review and meta-analysis looked at the longevity of
conventional and resin-modified glass ionomer restora­
tions as compared with composite resin restorations in
patients undergoing head and neck radiotherapy.300
Again, there were 4 studies selected with similar con­
clusions that the risk of failure was highest with con­
ventional glass ionomer followed by resin-modified glass
ionomer and the lowest risk of failure was with composite
resin restorations. The results of these 2 reviews suggest
that composite resin restorations combined with topical
fluorides may be the best alternative for root caries in
patients undergoing radiotherapy, but additional longer-
term studies are needed.
One study and 1 review reported on the performance
of the class of composite resins referred to as giomers.
The clinical trial included 182 children aged 4 to 8 years,
comparing occlusal-proximal ART restorations composed
of glass ionomer cement (Equaia Forte; GC) with re­
storations composed of giomer composite resin (Beautifil
Bulk Restorative; Shofu).301 Restoration survival after 24
months was 58.1% for glass ionomer cement and 49.1%
for the giomer composite resin, with no statistical dif­
ference between the 2 materials. A second systematic
review and meta-analysis compared giomer composite
resins to several alternative materials in permanent
teeth.302 Ten studies were selected, with 4 contributing to
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the meta-analysis. The results did not confirm any su­
periority imparted by the giomer composite resins other
than improvement in surface roughness when compared
with resin-modified glass ionomers.
Glass ionomer cement was compared with a silorane-
based composite resin in occlusal-proximal ART restora­
tions in primary molars of 192 children aged 4 to 9.303
After 24 months of service restoration survival was 82.7%
for glass ionomer cement and 88.9% for the silorane
composite resin, which was not significantly different.
Amalgam
Each year there are fewer publications relating to dental
amalgam, and published clinical studies are becoming
exceedingly rare. Two papers covered different aspects
of a prospective cohort study done in Norway. The first
evaluated changes in health complaints after the re­
moval of amalgam restorations.304 Thirty-two patients
with medically unexplained physical symptoms that they
attributed to amalgam restorations had all restorations
removed and replaced with non-amalgam materials.
Blood samples were collected before and 1 year after the
removal of all amalgam restorations to measure changes
in inorganic mercury, methylmercury, silver, and sele­
nium. Two comparison groups consisted of 28 patients
with unexplained physical symptoms not attributed to
amalgam and 1 group of healthy individuals (n=19).
These 2 comparison groups received no treatment. Not
surprisingly, the removal of amalgam was followed by a
reduction in inorganic mercury and silver in serum. The
intensity of health complaints decreased after amalgam
removal, but there was no clear evidence of a direct
relationship between mercury from amalgam exposure
and health complaints. The second paper coming out of
this study asked the question of whether the removal of
amalgam restorations in the patients with symptoms
attributed to amalgam was a cost-effective option for
treating these symptoms.305 Treatment costs and health
outcomes were documented at baseline and for 2 years
after amalgam removal for both the intervention and
normal care control groups. Both mean incremental cost
per patient and quality-adjusted life years were mea­
sured as outcomes. The estimated incremental cost per
quality-adjusted life year decreased with time, and
amalgam removal was found to be cost-saving over both
5- and 10-year projections. The authors pointed out that
these results provide one more aspect for consideration
in making healthcare decisions.
A systematic review attempted to evaluate the evi­
dence regarding mercury exposure and hypertensive
disorders of pregnancy.306 A total of 6 articles comprising
4848 patients, of which 809 experienced hypertensive
disorders. Most of these patients (4724, 97.4%) were ex­
posed to mercury via fish consumption and dental
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amalgam. Mercury biomarkers were measured in blood
in 4 studies and in urine in 2 studies. Two of the 6 studies
found a positive association between mercury and hy­
pertensive disorders, while the other 4 could not affirm
any association. Quality assessment rated 3 studies as
good and 3 as satisfactory, but one common deficiency
noted was the absence of adjusting for negative con­
founding factors, such as fish consumption.
One rather puzzling clinical study reported in 2022
was a trial in Pakistan that evaluated the 1-year reten­
tion of bonded amalgam sealants.307 The authors did not
elaborate on what advantage this would be expected to
provide over resin sealants, but not surprisingly, after
one year, 16% of the 137 bonded amalgam sealants were
completely lost compared with 7.8% of the 128 resin
sealants.
One rather broad systematic review compared the
longevity of amalgam and composite resin posterior
restorations in studies with at least 5 years of follow-up
and published in the last 15 years.308 A total of 17 arti­
cles were chosen for review, and factors related to the
performance were analyzed and compared. The global
conclusion by the authors stated that the success of re­
storations with more than 5 years of service is much
more due to the correct application of technique, the
operator’s skill and knowledge, and factors related to the
type of tooth, number of surfaces restored, and oral
hygiene of the patient.
One article reported on a survey of United States
dental schools to determine the latest teaching policies
and overall use of resin composites versus amalgam over
the years 2008 to 2018.309 Questionnaires were sent to
66 dental schools, with 34 responding to the teaching
policy questions and 17 providing use data. For the
policy questions, 76% reported assigning 50% or more
of preclinical restorative teaching toward posterior resin
composite. Fifty percent of the responding schools re­
ported devoting less than 25% of the time towards
teaching amalgam. Amalgam and composite resin use
were about equal in 2008 but moved to be significantly
more frequent for composites by 2009, with the trend of
increasing composite use continuing over the entire 10
years by all reporting schools.
By far, the most compelling literature in 2022 related
to amalgam has been discussions related to the
Minamata Convention on Mercury and the phase-out or
phase-down positions taken by parties to the agreement.
The fourth meeting of the Conference of the Parties to the
Minamata Convention on Mercury was held on March 21
to 25 in Bali, Indonesia. A series of side events were held
prior to that meeting, including one attended by the
American Dental Association, the FDI World Dental
Federation, the International Association for Dental
Research, and the American Association for Dental, Oral
and Craniofacial Research that outlined a position
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October 2023
supporting an accelerated phase-down rather than a total
phase-out, as had been proposed by some Parties to the
Convention.310 The American Dental Association also
revised all of its policy statements related to dental
amalgam in 2022, including support for the national
pretreatment standard for dental office wastewater,
strongly recommending that when using amalgam,
dentists only use precapsulated amalgam alloy, also re­
ferred to as encapsulated amalgam alloy, recommenda­
tions regarding the use of dental amalgam, and the
further promotion of the scientific assessment of dental
restorative materials.311 The recommendations for use
include a statement “that the ADA supports the globally
recognized need to reduce environmental mercury as set
forth in the Minamata Convention on Mercury (Sep­
tember 2019) as a common good, and recognizes the
responsibility of dentists to care for their patients’ well-
being, in keeping with the ADA Principles of Ethics and
Code of Professional Conduct.” The FDI World Dental
Federation also went through the exercise of revising its
policy statement in which it states as a principle that the
“FDI supports the World Health Organization for mini­
mizing mercury-related risks for patients, dentists and
dental teams and the environment during the placement
and removal of dental amalgam.”312 The FDI policy lar­
gely mirrors that of the ADA with regard to managing
amalgam waste via best practices and amalgam separa­
tors as well as rules regarding mercury hygiene, including
the use of only single-use encapsulated amalgam.
While momentum has been building for the ac­
celerated phase-down of amalgam, many countries
continue to struggle with educating their dental com­
munities regarding the appropriate actions to reduce the
environmental impact. An example of that is a cross-
sectional study of general practitioners in Pakistan,
where a survey tool was used to assess the use of
amalgam and its waste management.313 This survey of
550 dentists showed that amalgam was still used by
41.6% of the dentists, while 55% of them perceived it to
be a health risk. Unfortunately, most of the dentists
(76.3%) were unaware of proper disposal protocols, and
76.5% were unaware of any guidelines regarding the use
and disposal of amalgam.
A series of very compelling articles came out of the
United Kingdom in 2022 that provided a perspective on
some of the drivers, attitudes, and opinions that have
influenced the use of amalgam. Many of the lessons ar­
ticulated in these articles could be translated into many
countries and public health systems. The first discusses
the recently implemented European Union’s phase-down
by studying the current use of amalgam and its alter­
natives.314 A survey tool was distributed to more than 11
000 primary care dental clinicians in the UK questioning
the current provision of direct posterior restorations and
issues experienced with the different alternatives.
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493
Response rates were disappointingly low at 14% for
dentists and only 6% for dental therapists. Even so, these
providers reported that amalgam was the most used
material in posterior molar teeth and composite resin
most often in premolars. Clinicians, on average, booked
45% more time and charged 45% more when placing
composite resin as compared with amalgam. The 2 most
cited adverse outcomes from composite restorations were
food impaction and postoperative sensitivity. Re­
commended techniques, such as sectional metal matrices,
were associated with lower food packing, but longer
placement times for composite resin restorations.
Amalgam use was cited as being highest in the publicly
funded sector of UK primary care, and the authors noted
that major changes would be needed in the health ser­
vices structure and funding, as well as education on
posterior composite resin techniques to continue the
phase-down in the United Kingdom and other countries
where amalgam use is prevalent. The second part of this
paper described a study to identify the knowledge of the
phase-down and opinions of UK clinicians of a potential
phase-out of dental amalgam.315 This study used an e-
survey with an overall response rate of 13%. Knowledge
of the current phase-down activity was low, with only 3%
of clinicians able to identify all the patient groups in
whom amalgam use should be avoided. Postgraduate
education on posterior composite resin placement was
prevalent at 88%, but a large majority of providers had
personal and patient-centered concerns over the suit­
ability of alternatives to amalgam and lacked confidence
when placing composite resins in difficult situations. In
regression analysis, the best predictors of high confidence
in placing composite resins were being a private general
dentist or being primarily a composite resin user. Again,
the authors pointed out that the education of clinicians
alongside policy changes is necessary to enable a suc­
cessful phase-down and potential phase-out of amalgam.
A perspectives article in the British Dental Journal
provides a good overview of the issues faced worldwide
with the continued phase-down and eventual phase-out
of dental amalgam.316 This article points out that several
European Union countries have already mandated full
restrictions on amalgam, with others looking to follow.
There are many factors influencing a country’s ability to
accelerate the phase-down, including socioeconomic
crises, COVID-19 backlogs, availability and costs of al­
ternatives, patient preferences, and differences in ma­
terial performance. Without access to amalgam, we risk
the use of more crowns, more extractions, and greater
health inequalities. Regardless of considerable evidence
of safety, there is an imperative to remove mercury
globally as an environmental pollutant. A complete
phase-out, however, could also pose unintended con­
sequences, as we have yet to fully study the human and
environmental consequences of the alternatives. While
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we have best practices in place to control amalgam
waste, there are none developed for waste generated by
alternatives like composite resins. The author points out
that phasing down dental amalgam continues to be the
right thing to do, but until we have suitable alternatives,
policy changes, and investments, better outcomes from
prevention, and effective waste management for all
dental materials, dentists still need a full choice of ma­
terials to best meet patient needs.
A discussion of the environmental consequences
of amalgam is incomplete without the corresponding
consideration of the potential impacts of the alter­
natives. A paper provided a comprehensive review of
the potential pollutant risk to the environment from
the chemical compounds and ingredients found in
resin-based restorative materials.317 This discussion
included the principal pollutant compounds present
in the resin matrix; the degradation process of resin
composites and its consequences; the methods used
for the detection and quantification of monomer
elution and resin composite microparticles; and a
review of the release mechanisms of eluates and resin
composite microparticles into the environment. The
authors point out that the impact on the environment
and biodiversity by all these potential pollutants is
unknown. As resin composites become the mainstay
of restorative dentistry, mitigation strategies for re­
ducing the impact on the environment should be
considered and implemented.
Restoration repair and replacement
Three papers reported on the relative success of different
materials used to repair as well as the choice between
repairing and replacing an existing restoration. One
study examined the survival trajectory of crowns that
had been repaired in a dental school setting to de­
termine the factors associated with the greatest sur­
vival.318 A total of 1002 crown margin repairs were
tracked over 12 years, with 32.8% of repairs requiring
some reintervention. In a covariate model, only repair
material was significant with composite resin repairs
(RR=1.5: 95% CI: 1.02-2.10) and conventional glass io­
nomers repairs (RR=2.0: 95% CI: 1.40-2.73) more likely
to need reintervention than those done with amalgam.
The median survival time of a crown repair was 5.7 years
for amalgam, 5.3 years for a resin-modified glass io­
nomer, 3.2 years for composite resin, and 3.0 years for
conventional glass ionomer. A second study compared a
resin-based sealant (Clinpro Sealant; 3M) with a nano-
filled flowable resin (Filtek Flow Z350XT; 3M) for re­
pairing margin defects in resin composite restora­
tions.319 This prospective trial followed 54 patients with
162 restoration repairs using one of the two materials or
no treatment (control) over 36 months. It was refreshing
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to see a clinical design with a control group finally. The
results showed that margin staining increased for both
repair materials over time, and secondary caries were
better prevented with the nano-filled flowable resin
composite than with the sealant. The third paper pre­
sented a systematic review and meta-analysis evaluating
the risk of failure of repaired versus replaced direct
composite resin and amalgam restorations.320 Thirteen
studies were selected, with 3 included in the meta-
analysis. No difference was found in the risk of failure
between repaired and replaced defective direct restora­
tions (RR=1.21, 95% CI: 0.51-2.83). It was noted, how­
ever, that the risk of bias was high, and the certainty of
the evidence was very low. Such a warning is too often
included in systematic review conclusions.
OCCLUSION AND TEMPOROMANDIBULAR
DISORDERS
Dental occlusion
Mora-Zuluaga et al321 examined the relationship of
malocclusion with the presence of temporomandibular
disorders (TMDs) in children. 87 patients (from 4 to 14
years of age) were examined, and 77 patients studied
had malocclusions. 55 patients had TMD, and 67.3%
were female. The most frequent symptom of TMD was
unilateral articular noise at 33.8%, followed by pain in at
least one masticatory muscle at 26%. TMJ pain was
observed in 24.7% of the patients. There was a statisti­
cally significant relationship between the presence and
severity of TMD with the type of dentition and trans­
verse malocclusion, respectively. Mora-Zuluaga et al
concluded that the presence of TMD in children with
malocclusion presented in a high frequency.
Teng et al322 explored the relationships between the
occlusal plane and jaw deformity by measuring data
obtained from CBCT scans. Eighty participants with fa­
cial asymmetry and 42 normal (control) participants
were measured with a new 3-dimensional geometric
morphologic measurement system. Fifteen craniofacial
surfaces were marked at a point, line, or plane, mea­
suring correlation distances and angles to analyze the
relationship between jaw deformity and the inclination
of the occlusal plane and other relevant facial features. A
significant difference was found between the occlusal
plane of the jaw deformity and that of the normal group,
and a significant positive correlation between the degree
of mandibular deformity and the inclination of the oc­
clusal plane. In addition, statistically significant differ­
ences were found in the deviation of the chin vertex
from the midsagittal plane and the distance between the
midlines of the maxillary and mandibular central incisors
by more than 2 mm.
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October 2023 495

Structural alterations in the temporomandibular joint total score of 10 points. The change in condylar mor­
phology was defined by CRSS as follows: no change=10;
Structural alterations in the temporomandibular joint
mild=8-9; moderate=5-7; and severe=0-4.
(TMJ) can be assessed using CBCT and MR imaging.
Included in the analysis were 119 patients (89
Guercio Monaco et al323 discussed the correlation be­
women, 30 men, mean age 25.4 ±8.1 years). Normal
tween condylar size on CT and the position of the ar­
morphology was present in 25.2% (60/238) of condyles,
ticular disc on MRI of the TMJ. The position of the disc
mild morphological changes in 19.7% (47/238), mod­
in the TMJ is a critical factor associated with condylar
erate in 23.5% (56/238), and severe in 31.5% (75/238).
changes and alteration in mandibular growth in growing
The condyles with moderate morphological changes
patients. Based on the hypothesis that TMJ dysfunction
were inclined to be associated with a retrognathic and
affects the condylar morphology, this study aimed to
clockwise rotating mandible, shorter ramus height, and
quantitatively evaluate the size of the condylar head in
reduced mandibular length. Furthermore, the condyles
height (sagittal views), medial-lateral (M-L), and ante­
with severe morphological changes tended to be asso­
rior-posterior (A-P) dimensions (axial views) using CT
ciated with retrognathic and clockwise mandibular ro­
and to correlate these findings with the articular disc
tation, shorter ramus height, reduced mandibular
position in closed and opened mouth, using MRI.
length, larger mandibular angle, and maxillary retrusion.
This study evaluated 100 TM joints of 50 patients (37
These changes are likely due to the condylar remodeling
women, 13 men, median age 20.28 ±8.21 years). The
and subsequent shortening of the ramus. The larger
closed mouth view on MRI revealed 87 displaced discs.
gonial angle and shorter mandibular length observed in
There were statistically significant associations with
the severe group strongly suggest a close association
the horizontal condylar dimensions, the M-L, and the
between TMJ-OA development and mandibular mor­
A-P sizes of the condylar head. There was a significant
phogenesis. At the same time, the maxillary change in
correlation in the M-L size of the condylar head be­
the severe group might occur secondary to the man­
tween the normal position of the disc and DDNR. A
dibular retrusion. The male patients showed higher
significant correlation was also observed in the A-P size
proportions of condyles with normal and mild re­
of the condylar head between DDR (disc displacements
modeling, and the female patients showed a higher
with reduction) and DDNR (disc displacements without
proportion of severe remodeling. The status of the
reduction). The M-L and A-P sizes of the condylar head
condylar cortex was classified into continuous and dis­
were smaller in joints where the disc was displaced.
continuous groups and hypodense, normal density, and
Sun et al324 authored a paper discussing TMJ os­
sclerotic classifications. Most patients with a continuous
teoarthrosis (TMJ-OA), a degenerative process of non-
and normal density or sclerosed cortex showed no sig­
inflammatory origin closely related to condylar re-
nificant morphological or quantitative volumetric
modeling. Disc displacement is one of the common
changes. Condyles with a discontinuous and hypodense
causes of TMJ-OA or condylar remodeling. The patho­
cortex showed an increased probability of volume re­
logical process is characterized by the deterioration and
duction. These results suggest that after the condyle has
repair of the articular cartilage and subchondral bone.325
undergone a phase of cortical destruction during the
Bone resorption, sclerosis, osteophyte formation, and
initial stages of the disc displacement, the condyle can
various degrees of morphological changes in the condyle
reform smooth and continuous cortical bone.
may occur in TMJ-OA. Osteoarthrosis is a degenerative
joint disease involving the articular cartilage and sub­
chondral bone. TMJ-OA in teenagers frequently leads to
Articulation
functional impairment and Class II dentofacial defor­
mities. Orthodontic treatment or orthognathic surgery is Kois et al326 authored an article describing step-by-step
frequently needed to correct the associated dentofacial techniques to position the maxilla on an articulator using
deformities and improve masticatory function. the natural head position and a facial reference system for
Functional condylar remodeling is characterized by analog and digital workflows. A photographic technique
stable condylar morphological changes, stable ramus captures the natural head position and allows the clin­
height, stable occlusion, and normal growth. Dysfunctional ician to align a 2-dimensional reference photograph with
remodeling is characterized by accelerated TMJ morpho­ the maxillary intraoral digital scan and the virtual ar­
logical changes, decreased ramus height, and mandibular ticulator. Using this reference photograph, the clinician
retrusion. can record and communicate to the dental laboratory
A condylar remodeling scoring system (CRSS) was technician the maxillary arch position in relationship with
established based on 11 anatomical landmarks. For each the facial references and transfer the additively manu­
increase in anatomical regions involved in the condylar factured casts in the same facial orientation for mounting
morphological change, 1 point was subtracted from the and analysis virtually or in an analog articulator.

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496
Standardized transfer attachments are added to cast
files for printing and mounting in an analog articulator.
The files with the transfer attachments are then printed
and attached to newly designed transfer devices, com­
pleting a gypsum-less mounting on the analog articulator
that can be used for facial analysis and treatment plan­
ning. This functional and esthetic digital facebow transfer
to analog mounting protocol incorporates digital transfer
techniques for dental office analog implementation.
Imaging
Minston et al327 authored a paper that aimed to identify
potential clinical and radiological predictors associated
with the outcome of discectomies. This retrospective
observational study reviewed preoperative CBCT images
and medical records of 62 patients who had undergone
discectomy because of disc displacement with reduction
(DDwR), disc displacement without reduction (DDwoR),
systemic arthritis (SA), or joint hypermobility.
The success odds ratio was 11 times higher in pa­
tients with painful DDwR versus that of SA. Without a
subchondral pseudocyst, there were 5.2 times higher
odds of having a successful subjective outcome.
Extensive bone apposition on the temporal joint com­
ponent indicated a 9.3 times higher likelihood of a failed
objective outcome.
Based on CBCT findings related to the objective
outcome failure, predictors of importance were extensive
bone apposition on the temporal joint component and
condylar subchondral pseudocysts for the subjective
outcome failure. Based on the clinical findings related to
the objective outcome failure, predictors of importance
were a combined diagnosis of SA and DDwR.
Fan et al328 reported that degenerative joint disease
(DJD) could be associated with disc displacement (DD)
in TMD patients. However, the relationship between
different types of DDs and DJD remains to be seen.
Radiographic data from 69 men and 232 women were
collected for analysis. CBCT was used to diagnose DJD,
with criteria including erosion, osteophytes, generalized
sclerosis, and cysts in the joint. Sagittal and coronal
MRIs evaluated 8 types of DDs. The results showed that
anteriorly displaced discs without recapture had a sig­
nificantly higher prevalence of DJD than those with
reduction.
Temporomandibular joint surgery
Hua et al329 discussed different techniques to repair
anteriorly displaced discs (ADD). Anterior disc displace­
ment is a common TMD. The clinical manifestations in­
clude joint pain, clicking, and limited mouth opening. In
some patients, conservative treatment, such as medica­
tions, physiotherapy, and low-intensity pulsed ultra­
sound, can achieve good results through masticatory
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
biofeedback. However, some patients may experience
condylar resorption with anterior disc displacement. In
addition, when ADD happens in growing patients, con­
dyle growth may be affected, resulting in mandibular/
facial asymmetry and retrognathia.
Disc repositioning gained more stable results when
combined with orthognathic surgery than when disc
repositioning was not performed. Disc repositioning can
occur with an anchor placed in the condyle, and the disc
can be sutured to the anchor. A disc suturing technique
that sutured the disc to the posterior articular capsule is
another option to reposition the disc over the condyle.
The study evaluated TMJ and jaw stability after disc
repositioning by open suturing when combined with
orthognathic surgery.
Seventeen patients with 20 hypoplastic condyles
were included in the study. Among them, 12 joints had
disc repositioning by open suturing and 8 by a mini-
screw anchor. After an average follow-up of 18.1
months, both the TMJ disc and jaw position were stable
in the 2 groups, except 2 discs moved anteriorly in each
group. The overall condylar bone resorption was 8.3% in
the open suturing group and 12.5% in the mini-screw
anchor group. Disc repositioning by open suturing can
achieve both TMJ and jaw stability for hypoplastic con­
dyles when combined with orthognathic surgery.
Qin et al330 explored 2 therapeutic approaches for
skeletal Class II patients with temporomandibular de­
generative joint disease. Forty-seven patients were in­
cluded in this study. The anterior repositioning splint
(ARS) group was treated with TMJ disc surgery followed
by an ARS and camouflage orthodontic treatment. The
stabilization splint (SS) group was treated with an SS
followed by orthodontic treatment combined with or­
thognathic surgery. In addition, cephalometric analysis
of lateral radiographs and measurements of condylar
height were evaluated before and after splints.
In group ARS, mandibular advancement was ob­
served after treatment in 21 of 24 patients (87.5%). TMJ
disc surgery followed by postoperative ARS could pro­
mote condylar bone remodeling and regeneration. The
severity of skeletal Class II and the hyper-divergent
growth pattern were alleviated, which sustained ca­
mouflage orthodontic treatment instead of orthognathic
surgery for borderline patients.
In group SS, 18 of 23 patients (78.3%) showed a
backward change tendency. After SS therapy, a much
more retrognathic but true mandible position is re­
vealed. Subsequently, combined treatment involving
orthodontics and orthognathic surgery should be con­
sidered based on TMJ anatomy.
Ding et al331 discussed heterotopic ossification (HO)
since it is a serious complication leading to alloplastic
temporomandibular joint replacement (TJR) failure. Se­
vere HO might result in pain and limited mouth
Cagna et al
October 2023
opening after surgery. Therefore, it is necessary to clarify
its clinical and imaging manifestations. Patients who
underwent standard TJR with fat graft and at least 1-
year follow-up were included. Within 1 week after the
operation, joint space was measured and compared
between HO and non-HO TJRs. Maximum incisal
opening (MIO), pain, and QoL were recorded, and their
relevance with HO was analyzed statistically. The study
included 81 patients involving 101 TMJs with a mean
follow-up time of 22.9 months. HO after alloplastic TJR
with fat graft was not severe apart from HO from both
the mandibular ramus and articular eminence, which
affected 3% of the patients in the study.
Tissue engineering
Singh et al332 discussed tissue engineering related to the
development of a TMJ disc implant. An ideal TMJ disc
implant should have some desirable properties. The first
property is to withstand functional masticatory loads for a
considerably long period or loading cycles. The second
factor is that the disc implant should have a similar his­
tological, cellular, and extracellular matrix profile. The
third factor should be high biocompatibility and feasibility
to produce, and lastly, the disc implant should have fa­
miliar mechanical properties of the native disc. The
challenges related to disc implants today include early
scaffold degradation, an immunologic response, difficulty
moving from animal models to clinical applications, in­
adequate size in animal models, biosafety concerns due to
the proximity of the brain, and preliminary biomechanical
studies. Due to these challenges, disc implants are not
currently near completion, but they represent a promising
future in disc replacement strategies.
SLEEP-DISORDERED BREATHING
The objective of this review will be to bring an improved
understanding of the discipline of dental sleep medicine
as it stands today. Improved research with more robust
studies is needed as the field matures into its rightful
place in medicine. Studies do not clearly describe the
design details of the appliance used, nor do the authors
describe the calibration method. Both omissions are
slowing the forward progress of the field.
Oral appliance therapy
A network meta-analysis explored the comparative ef­
ficacies of mandibular advancement devices (MADs) in
treating OSA.333 MADs were classified according to the
mechanism of action within qualifying RCTs. Data in­
cluding AHI, Epworth sleepiness scale (ESS), nadir
oxygen saturation (minSaO2), and sleep efficiency (SE
%) were then meta-analyzed, and comparative ranking
Cagna et al
497
of different devices was calculated based on P scores,
similar to the Surface Under Cumulative Ranking Curve
(SUCRA). Various brands of MADs were also analyzed.
No statistically significant differences were realized
among MADs in the examined outcomes. However,
some devices were ranked higher than others in several
outcomes based on P values derived from point esti­
mates and standard errors of network estimates. The
most excellent P scores were attained for attached
midline traction (P=.84) and unattached bilateral inter­
lock (P=.78) appliances for the decrease in AHI; attached
bilateral traction (P=.78) and unattached bilateral inter­
locking (P=.76) for ESS; monobloc (P=.91) and un­
attached bilateral interlocking (P=.64) for minSaO2; and
unattached bilateral interlocking (P=.82) and attached
bilateral traction (P=.77) for SE%.
Noteworthy findings in the meta-analysis based on
brands of MADs in the limited patients where they were
specified were the outcomes of SomnoDent Flex, TAP, and
IST in their impacts on AHI reduction, with P values of .94,
.83, and .82, respectively. Monobloc reduced supine-AHI
the most (-44.46; CI: -62.55 to -26.36; P=.99), and un­
attached bilateral interlocking had the most significant
effect on REM-AHI (-11.10; CI: -17.10 to -5.10; P=.87). The
authors concluded that clinically (but not statistically) sig­
nificant differences existed among MADs in terms of their
relative efficacy when analyzed for different OSA therapy
outcomes and sleep apnea phenotypes.
Another study examined the therapeutic efficacy of
custom-made MAD in controlling primary snoring (PS)
and mild OSA and correlated it with anatomical al­
terations demonstrated via imaging tests.334 Individuals
(n=17) diagnosed with OSA, or primary snoring, were
enlisted and treated with MADs. Changes were eval­
uated with polysomnographic (PSG) testing, ESS, and
computed tomography (CT) scanning. Testing was done
at baseline and after MAD use. Anteroposterior di­
mensions were made in the sagittal at the hard palate,
glottis, and supraglottic levels along the hard palate axis.
Afterward, measurements were recorded in the axial
plane at the same levels along the hard palate axis. From
the 6 recorded measurements, the caliber of the airway
increased by 5. These outcomes were only significant in
two areas (sagittal hard palate and axial supraglottic).
Snoring was alleviated in 16 of the 17 patients; 12 in­
dividuals demonstrated a correct airway opening at the
hard palate level. Furthermore, daytime sleepiness de­
creased in all subjects. It was concluded that findings
suggest that sagittal hard palate and axial supraglottic
opening following MAD are mainly responsible for
eliminating snoring and improving OSA.
Treatment for OSA has been suggested to reduce
cardiovascular (CV) risk. However, at this point,
knowledge is limited about the difference in this risk
reduction between MADs and continuous positive
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airway pressure (CPAP) therapy. This RCT compared
the CV effects of MAD and CPAP treatment in subjects
with moderate OSA.335 Patients with an AHI of 15-30
events/hr were randomized to CPAP or MAD therapy.
At baseline and 12-month follow-up, 24-hour ambula­
tory blood pressure (BP) recordings and laboratory
measurements were performed; ambulatory BP data
included 24-hours, daytime, and nighttime systolic BP,
diastolic BP, and heart rate recordings. Laboratory
measurements comprised serum lipid values, creatinine,
high-sensitivity C-reactive protein, plasma glucose, he­
moglobin A1c glycated hemoglobin, proinflammatory
cytokines, soluble receptor for advanced glycation end-
products, chemokines, and adhesion molecules.
Of the 85 participants with moderate OSA, data were
available for 54 patients (24 MAD, 30 CPAP) at 12-
month follow-up, demonstrating that AHI significantly
decreased with either method. In the oral appliance arm,
soluble receptors for advanced glycation end-products
and glycated hemoglobin were significantly higher at 12
months than pre-treatment levels. No significant
changes were elucidated between MAD and CPAP
therapy for all outcomes. The investigators concluded
that treatment of individuals with moderate OSA with
either MAD or CPAP had no profound effects on major
cardiovascular risk factors after 12 months.
Oral appliance therapy (OAT) is recognized as a
well-tolerated alternative to CPAP but may need to be
more efficacious. A major clinical challenge is the in­
ability to predict OAT responders accurately. This pro­
ject’s authors developed a model to estimate OSA
pathophysiological endotypes and applied the physio­
logical-based model to predict response to OAT.336
Sixty-two men and women with OSA (29-71 years)
were enlisted to examine the efficacy of a novel oral
appliance (OA) device. In-lab PSG followed by an OAT
efficacy study was performed. Seven variables from the
diagnostic study, plus age and body mass index (BMI),
were included in the machine learning-based model to
predict OAT response based on standard AHI defini­
tions. The model was initially trained on data from the
first 45 participants using 10-fold cross-validation. A
blinded independent validation was then carried out for
the remaining 17 participants.
The mean accuracy of the trained model to predict
OA treatment responders versus nonresponders (AHI
<5/hr) using 10-fold cross-validation was 91 ±8%. In the
blinded independent validation, 100% (AHI <5/hr); 59%
(AHI <10/hr); 71% (50% AHI reduction); and 82% (50%
reduction in AHI to <20/hr) of the 17 participants were
correctly designated for each of the treatment outcomes
definitions, respectively. They noted that further eva­
luation in larger clinical data sets is warranted. The
outcomes highlight the potential to use routinely col­
lected PSG and clinical data with machine learning-
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Volume 130 Issue 4
based approaches underpinned by OSA endotype con­
cepts to assist prediction of outcomes of OAT for those
with OSA.
Mandibular advancement devices are recognized as a
noninvasive therapy option for individuals with OSA
and act to increase the upper airway (UA) volume.
However, the exact mechanism of therapeutic action
remains unclear. This study set out to explore MAD
mechanisms employing function imaging that combines
imaging techniques and computational fluid dynamics
and assess associations with treatment outcomes.337
One hundred individuals with OSA were prospectively
involved and treated with a custom-made MAD at a
fixed 75% protrusion. Low-dose CT scan was made with
and without oral appliances for computational fluid
dynamics analysis. Subjects underwent PSG at baseline
and 3-month follow-up to assess treatment efficacy.
Treatment response was defined as AHI reduction
≥ 50%. Seventy-one patients completed both 3-month
follow-up PSG and low-dose CT scan with computa­
tional fluid dynamics analysis. MAD therapy sig­
nificantly decreased the AHI (16.5 events/hr, CI: 10.4-
23.6; to 9.1 events/hr, CI: 3.9-16.4; P<.001) and sig­
nificantly improved the total UA volume (8.6 cm3, CL:
5.4-12.8; versus 10.7 cm3, CI: 6.4-15.4; P=.003), espe­
cially the velopharyngeal volume (2.1 cm3, CI: .5-4.1;
versus 3.3 cm3, CI: 1.8-6.0; P<.001). Sub-analysis in re­
sponders and nonresponders only demonstrated a sig­
nificant increase in the total UA volume in responders. It
was concluded that MAD acts via increasing total UA
volume, primarily due to increased velopharyngeal vo­
lume. Responders exhibited a significant improvement
in UA volume with MAD use, while there was no sig­
nificant increase in nonresponders. This project adds
evidence to implement functional imaging with CT fluid
dynamics in the routine prediction of MAD outcomes.
OSA is associated with CV comorbidities, including
left ventricular (LV) hypertrophy. It is unknown whether
sleep apnea is independently responsible for this re­
modeling. CPAP partially reverses LV remodeling, but
data about the effect of MADs on LV hypertrophy are
scant. This prospective trial sought to explore the impact
of mandibular advancement therapy on LV function and
geometry in OSA patients.338 Participants were tested at
baseline and 6 months of therapy via home sleep apnea
testing (HSAT), 24-h ambulatory BP monitoring and 2-
dimensional Doppler and tissue Doppler echocardio­
graphy. Sixty-three individuals (age: 49 ±11 years; BMI:
27.0 ±3.4 kg/m2; baseline AHI HSAT=11.7 events/hr, CI:
8.2-24.9) completed the 6-month follow-up evaluation.
Generally, BP values and LV function were within
normal ranges at baseline and did not change with MAD
therapy. However, the interventricular septum thickness
was at the upper limits of normal pretreatment and
exhibited a significant decrease at follow-up
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October 2023
(11.1 ±2.1 mm versus 10.6 ±2.0 mm, P=.03). This sig­
nificant improvement was only demonstrated in treat­
ment responders. No correlation was found between the
reduction of interventricular septum thickness and the
change in blood pressure. The investigators concluded
that OSA is an independent factor in the pathophy­
siology of LV hypertrophy in patients with mild obesity
and normal BP. MAD therapy can significantly impact
LV changes.
Mandibular advancement device therapy is the most
common second-line treatment for OSA but may be
ineffective in a subgroup of patients. A systematic review
and meta-analysis was performed to elucidate predictors
of oral appliance efficacy for OSA in adults, especially
quantitative analysis in subgroups based on responder
criteria in the studies and type of device.339 Databases,
including PubMed, EMBASE, Scopus, Web of Science,
and Cochrane, were searched to elucidate potentially
relevant studies published through December 2021. The
search identified 1343 potential papers; 99 references
met inclusion criteria and were included in the review,
and 60 were meta-analyzed. Newcastle-Ottawa scale
and Cochrane scale were used to examine the quality of
studies. According to meta-analysis and considering a
low to moderate evidence profile according to the
grading of recommendations assessment, development,
and evaluation (GRADE) scale, responders were
younger with smaller neck circumference and lower
BMI. Responders had shorter maxillary length, lower
anterior and posterior facial height, reduced distance
from the hyoid bone to the third cervical vertebra,
shorter airway length, smaller minimum airway cross-
sectional area, and a higher minimum oxygen saturation
during sleep. Responders required a lower optimal
CPAP pressure than non-responders. The type of ad­
vancement device did not impact the results of the
meta-analysis. The criterion “AHI <10 and reduction of
AHI >50%” is the one that provides the bulk of sig­
nificance for several parameters. It was concluded that
this criterion should be considered for future studies to
predict MAD therapy outcomes for OSA.
Oxygen saturation indices demonstrate a strong
correlation with long-term health outcomes. However,
evidence of the relationship between decreased re­
spiratory events and increased oxygenation levels fol­
lowing OAT remains sparse. This project aimed to verify
the relationship between the decrease in AHI and
oxygen saturation levels following oral appliance treat­
ment; PSG and clinical parameters associated with im­
proving oxygen desaturation were evaluated.340 Forty-
eight individuals with OSA who were using MAD with
pretreatment and post-treatment PSG were categorized
into 3 responder categories according to change in AHI
and minimum O2 post-treatment: responderAHIonly
(decrease in AHI ≥50% but increase in min O2 level of
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499
<4% or decrease; responderMinO2only (increase in min O2
of ≥4% but the reduction in AHI of <50% or increase);
and responderCongruous (decrease in AHI of ≥50% and
elevation in min O2 level of ≥4%). Various demographic
and PSG parameters were statistically compared among
the groups. There were 26 (54.17%) respondersAHIonly, 9
(18.75%) respondersMinO2only, and 13 (27.08%) re­
spondersCongruous. Pretreatment min O2 was sig­
nificantly lower in respondersMinO2only. A higher
pretreatment min O2 demonstrated a significant corre­
lation with a smaller change in mean O2 (ι=-.486) and
min O2 (ι=-.764) with therapy. Pretreatment min O2
showed the greatest ability to predict those showing a
≥ 4% min O2 elevation with treatment. The investigators
concluded that certain patients do not exhibit sufficient
decreases in hypoxemia despite AHI improvements.
Therefore, pretreatment min O2 should be considered in
MAD planning regarding its close relation to improve­
ments in oxygenation levels with therapy.
A different study wanted to compare MAD success
rates using in-lab remotely controlled mandibular po­
sitioner (RCMP) manual titration performed in White
and Chinese participants with OSA to determine the
optimal protrusive position (OPP) for those with
OSA.341 Manual RCMP titration occurred during in-lab
PSG using procedures previously described for partici­
pants. The success rate was determined based on clas­
sical success criteria or those previously used for RCMP
titration. One hundred-sixty participants were involved
in the study, and definitive data were acquired from 141
(71 Chinese and 70 White participants with OSA).
Chinese individuals were significantly younger, with
lower BMI and more severe OSA than their Canadian
counterparts. Among those with predicted success, the
OPP expressed in % of full protrusive position did not
differ between the 2 groups. Chinese ethnicity, younger
age, and lower baseline AHI were significant determi­
nants of RCMP success. Multivariate analysis showed
that only ethnicity and AHI were found to significantly
account for success; the odds ratio for success in Chinese
compared to Whites corrected for AHI was 3.7 and 4.6
depending on the success criteria employed. It was
noted that the predicted success rate of MAD according
to RCMP titration was greater in Chinese, even though
the AHI was greater.
Many types of MADs are available to treat patients
with OSA, including non-custom and custom appli­
ances. However, studies have yet to be performed to
elucidate whether a non-custom device could predict
the treatment success of a custom MAD. This single-
center prospective randomized crossover study explored
the potential of a new generation of non-custom MAD
by comparing its effectiveness with a custom device.342
The researchers hypothesized that device effectiveness is
comparable to objective (PSG) and subjective
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500
(questionnaires, adherence, and patient satisfaction)
outcomes. A consecutive series of patients with OSA
were randomized to start with the non-custom or
custom appliance. Both MADs were used for 12 weeks,
followed by PSG w device in site and questionnaires.
After the first 12 weeks of follow-up, a washout period
of 1 week was applied. Equal effectiveness was defined
as no significant differences in subjective and objective
outcomes between both appliances. Fifty-eight in­
dividuals were included; 40 completed the entire pro­
tocol. The median AHI significantly decreased from 16.3
events/hr (CI: 7.7-24.8) to 10.7 events/hr (CI: 5.6-16.6)
with the custom MAD (P=.010) and to 7.8 events/hr (CI:
2.9-16.1) with the non-custom device (P<.001). Self-
reported outcomes significantly improved in both
groups. No significant differences were elucidated be­
tween the devices. They concluded that the effectiveness
of a non-custom and custom MAD is comparable,
suggesting that a non-custom device can be employed
as a selection tool for mandibular advancement therapy
eligibility to enhance treatment outcomes.
Mouth breathing increases upper airway (UA) col­
lapsibility, leading to reduced efficacy of OSA therapy.
This group hypothesized that employing MADs in­
creases mouth breathing and using an adhesive
mouthpiece (AMT) to prevent mouth breathing in
conjunction with MAD can improve treatment efficacy.
A prospective crossover pilot study evaluated the effec­
tiveness of MAD plus AMT compared with MAD
alone.343 Adults with an AHI between 10 and 50 events/
hr at screening were randomized to no treatment
(baseline), MAD treatment, AMT treatment, and MAD
+AMT therapy. As a primary analysis, absolute AHI was
examined between MAD and MAD+AMD arms. Sec­
ondary analyses, including quantifying the percent
change in AHI, percentage of complete (AHI <5 events/
hr) and incomplete (5-10 events/hr) responders, and the
efficacy of AMT alone in comparison with other treat­
ment arms. Twenty-one participants participated
(baseline AHI=24.3 ±9.9 events/hr). The median AHI
(interquartile range) for the MAD group was 10.5
events/hr (CI: 5.4-19.6), and the MAD+AMT group was
5.6 events/hr (CI: 2.2-11.7; P=.02). Seventy-six percent
of participants attained an AHI <10 events/hr in the
MAD+AMT arm versus 43% in the MAD arm (P<.01).
Lastly, the observed effect was similar in moderate-se­
vere OSA (AHI ≥15 events/hr) in terms of absolute re­
duction and treatment responders, and AMT alone did
not significantly decrease the AHI compared with
baseline. The investigators concluded combining an
adhesive mouthpiece and MAD is more effective than
MAD alone. These results may help augment clinical
decision-making for patients with OSA.
MADs are used as an alternative to CPAP for pa­
tients with OSA, but specific data on adherence to MAD
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Volume 130 Issue 4
therapy are sparse. A systematic review of RCTs with
meta-analysis and meta-regression examined the
dropout rate and commitment of individuals with OSA
to various custom-made (CM) and non-custom made
(NCM) mandibular advancement therapies.344 Elec­
tronic database searches included MEDLINE, Cochrane
Database of Systematic Reviews, Scopus, LILACS, and
Web of Science. RCTs exploring the compliance to
custom and non-custom MADs treating adult patients
with OSA were selected. The quality of evidence was
assessed via GRADE and the risk of bias by the Co­
chrane Collaboration’s tool for assessing the risk of bias
in RCT. The dropout rate was calculated, and adherence
to MAD therapy in terms of hours per night and nights
per week was derived from each study. Thirty-two RCTs
were used; the risk of bias was low in most of the stu­
dies, and GRADE scores showed that the quality of
evidence varied from very low to moderate. The meta-
analyses showed that the average dropout rate was not
significantly different between CM and NCM devices;
the overall mean dropout rate was.171 (CI: .128-.213),
with a mean follow-up of 4.1 months. Adherence was
significantly greater for CM MADs at 6.418 hrs/night
(CI: 6.033-6.803) compared with NCM MADs at 5.107
hrs/night (CI: 4.324-5.890). The meta-regression de­
monstrated that the dropout rate increases significantly
over time (P<.05). The reviewers concluded that there
was very low to moderate quality of evidence that the
dropout rate of MAD treatment was similar among CM
and NCM MADs, adherence significantly decreased
over time and CM devices had greater hours/night use
compared with NCM MAD.
Pathophysiology and medical implications
A review explores the transition of OSA pathophy­
siology to an integrative disease model.345 OSA is
characterized by repeating episodes of upper airway
(UA) obstruction during sleep; the primary abnormality
represents the inability of UA dilating muscles to with­
stand the negative pressures generated within the UA
during inspiration. Myriad factors contribute to the
narrowing of the oropharynx, including craniofacial
anatomy, excess soft tissue deposition in the neck, and
rostral fluid shift in the recumbent position, lending to
elevated collapsing forces within the airway. The coun­
teracting actions of UA dilator muscles, especially the
genioglossus, are negatively impacted by sleep onset,
inadequate genioglossus response, ventilatory instability
(especially following arousal), and loop gain. Sleep
apnea is often associated with comorbidities that include
metabolic, CV, renal, pulmonary, and neuropsychiatric
issues. Evidence accumulates for bidirectional interac­
tions between OSA and comorbidity, especially for heart
failure, metabolic syndrome, and stroke. An in-depth
Cagna et al
October 2023
understanding of the complex pathophysiology of OSA
supports developing treatments focused on pathophy­
siological endotypes. It promotes a move toward preci­
sion medicine as a potential alternative to CPAP therapy
in selected individuals.
This project created a method for observing voluntary
swallowing during sleep using PSG, recognizing that
existing information on the subject is rare.346 Poly­
somnography results were gathered for twenty control
participants and 60 patients with OSA (n=20 each for
mild, moderate, and severe disease). Simultaneous in­
creases in the electromyographic potentials of the sub­
mental and masseter muscles (coactivation) and reduced
oronasal airflow (SA) were extracted as “swallowing.”
The cough reflex that occurred during sleep was isolated
as “aspiration.” The frequency of swallowing events was
evaluated among the different OSA groups; then, mul­
tivariate regression analysis was conducted. The mean
frequency of coactivation with SA in controls was 4.1
events/hr, and that without SA was 1.7 events/hr. These
frequencies increased with the severity of OSA during
non-rapid eye movement (NREM) sleep. The distance of
the hyoid bone to the Frankfurt plane was associated
with the frequency of coactivation with (β=.298, P=.017)
and without SA (β=.271, P=.038). The frequency of
coactivation without SA was associated with aspiration
(β=.192, P=.042). The investigators concluded that new
insights had been provided regarding the interaction
between swallowing and aspiration during sleep. It was
found that the greater the distance from the hyoid bone
to the Frankfurt plane, the greater the coactivation
without SA, which could contribute to aspiration during
sleep.
OSA has significant health consequences but can be
difficult to treat. For many treatment modalities, efficacy
is impacted by the severity of underlying pharyngeal
collapsibility, yet there is no accepted clinical means to
assess it. This study supplies insight into which PSG
surrogate measures of collapsibility are valid, applicable
across the population, and predictive of therapeutic
outcomes.347 Seven favorable PSG-derived surrogate
collapsibility candidates were examined: Vpassive (flow at
eupneic ventilatory drive); Vmin (ventilation at nadir
drive); event depth (depth of average respiratory event);
oxygen desaturation slope and mean oxygen desaturation
(events-related mean); Fhypopneas (fraction of events
scored as hypopneas); and apnea index. The evaluation
consisted of validation by comparison to physiological
standard collapsibility values (critical closing pressure,
Pcrit); capacity to identify greater collapsibility with
older age, male sex, and obesity in a large community-
based cohort (Multi-Ethnic Study of Atherosclerosis,
MESA); and prediction of treatment efficacy (oral ap­
pliances and pharmacological pharyngeal muscle sti­
mulation using atomoxetine-plus-oxybutynin). Pcrit was
Cagna et al
501
significantly correlated with Vmin (r=-.54), event depth
(r=.49), Vpassive (r=-.38), Fhypopneas (r=-.46), and apnea
index (r=-.46; all P<.01) but not others. All indices elu­
cidated greater collapsibility with male sex, age, and
obesity, except Fhypopneas and apnea index, which were not
associated with obesity. Fhypopneas and apnea index were
associated with OA and atomoxetine-plus-oxybutynin
efficacy (both P<.05). The authors noted that among the
candidates examined, event depth, Fhypopneas, and apnea
index were identified as preferred pharyngeal collapsi­
bility surrogates to use in clinical settings.
OSA is defined by pauses in breathing during sleep,
but daytime breathing dysregulation may also be present.
Sleep may be associated with breathing instability in
OSA, otherwise masked by behavioral influence during
wakefulness. A breath-hold (BH) challenge has been
used to exhibit breathing instability. One measure of
breathing instability is breathing rate variability (PRV).
This trial sought to evaluate BRV during rest and in re­
sponse to BH in OSA.348 Sixty-two individuals partici­
pated, including 31 untreated OSA (respiratory event
index or REI=20 ±15 events/hr; 12 women, age 51 ±14
years, BMI=32 ±8 kg/m2) and 31 controls (17 women; age
47 ±13 years, BMI 26 ±4 kg/m2). Breathing movements
were gathered via a chest belt for 5 min of rest and during
a BH protocol (60 s baseline, 30 s BH, 90 s recovery; 3
repeats). The breathing movements calculated the
median breathing rate (BR) and interquartile BRV at rest.
Change in BRV during BH recovery from baseline was
also calculated. OSA versus control groups were com­
pared by using analysis of covariance with age, sex, and
BMI as covariates.
During rest, BRV was 10% greater in OSA than in
controls (P<.05). In response to BH, BRV increased by
7% in OSA compared with 1% in controls (P<.001).
Resting BR was not significantly different in both
groups, and sex and age did not significantly influence
interactions. BMI was associated with BR at rest (P<.05)
and change in BRV with BH (P<.001), but no significant
BMI-by-group interaction was noted. It was concluded
that the findings suggested that breathing instability, as
reflected via BRV, is high in OSA during wakefulness,
both at rest and in response to a stimulus. Breathing
instability combined with elevated BP variability in OSA
may indicate a compromised cardiorespiratory con­
sequence in OSA during wakefulness.
A different study set out to compare the UA’s ana­
tomic and aerodynamic characteristics of edentulous
older adults with mild, moderate, and severe OSA; and
to explore the correlation between the severity of OSA
and the anatomic and aerodynamic characteristics of the
UA in edentulous patients.349 NewTom5g CBCT scans
were performed and analyzed on 58 edentulous in­
dividuals with mild, moderate, and severe OSA. Com­
putational models of the UA were reconstructed
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502
according to CBCT images, and the anatomical and
aerodynamic characteristics of the upper airway were
evaluated by an observer blind to disease severity.
Pearson correlation analysis was used to determine the
correlation between AHI and the anatomic and aero­
dynamic characteristics of the UA. Compared with
edentulous patients with mild and moderate OSA, in­
dividuals with severe sleep apnea have a more hour­
glass-shaped UA. AHI was significantly correlated with
the UA length, shape, and minimum cross-sectional
area. During inspiration, the average airflow velocity
with the upper airway of the severe OSA edentulous
patients was greater than that of patients with less se­
vere disease. During both inspiration (P=.024) and ex­
piration (P=.038), AHI was significantly correlated with
maximum velocity (P=.05) and airway resistance. The
investigators concluded that edentulous patients with
severe OSA exhibit a more hourglass-shaped UA, and
the findings suggest that during inspiration, the airflow
travels faster in these individuals than in those with
mild-moderate OSA.
Inspiratory flow limitation (IFL) is characterized by a
flattening of individual breaths on the airflow/time
tracing of a PSG. It signifies noninvasive elevated upper
airway resistance (UAR). In isolation, an IFL “event”
lacks definition, and the ability to reliably identify event
occurrence has not been tested. IFL events and their
association with immediate physiological responses (as
well as the impact of characteristics including age, sex,
sleep stage, sleepiness, and event duration on the as­
sociation of such outcomes) have not been previously
examined. Patients exhibiting symptoms with normal
to mildly elevated AHI with predominant IFL on PSG
may benefit from treatment. This project was con­
ducted to test the reproducibility of identifying IFL
events and their termination and to elucidate the fre­
quency of the immediate physiological response to
their happening, including desaturation, electro­
encephalography (EEG) arousal, and elevated heart
rate (HR).350 Fifty-eight participants with OSA under­
went full diagnostic PSG. IFL events and their termi­
nation were manually scored using predefined rules
from the unscored nasal cannula flow channel alone.
They were examined for EEG arousal, oxygen desa­
turation of ≥ 3%, and HR increase.
Interscorer reliability was acceptable, with 82% ±3%
average agreement for occurrence. Of all IFL events, 24%
(regardless of definition) were not associated with an EEG
arousal rise in HR or O2 desaturation. Of all IFL events
recorded, 25% led to O2 desaturation, 40% were asso­
ciated with an EEG arousal, and 55% exhibited an increase
in HR; 67% caused either an EEG arousal or an increase in
HR. Responses were demonstrated to occur either in iso­
lation or in combination. IFL events that terminated with
≥2 non-IFL breaths, one of which had a 200% increase in
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
amplitude, were significantly associated with O2 desa­
turation, EEG arousal, and elevation of HR compared with
events that ended in one non-IFL breath. IFL events that
demonstrated a >50% reduction in flow amplitude com­
pared with baseline were significantly associated with O2
desaturation compared with events with a ≤30% reduction.
It was concluded that most IFL events resulted in im­
mediate physiological responses, and no single con­
sequence predictably occurred following every event. They
proposed a framework that can include scoring IFL events
to evaluate the diagnosis and severity of OSA. They sug­
gest that no single consequence be relied on to define IFL
as a respiratory event. The relationship of IFL events to
OSA outcomes remains to be evaluated.
Rapid eye movement (REM) sleep is associated with
decreased ventilation and elevated OSA severity than
NREM sleep for reasons that have not been entirely
determined. This trial used direct physiological mea­
surements to elucidate whether the pharyngeal com­
promise in REM sleep OSA is most consistent with (1)
withdrawal of neural ventilatory drive or (2) deficits in
pharyngeal pathophysiology per se (that is, elevated
collapsibility and reduced muscle responsiveness).351
Sixty-three patients with OSA underwent PSG with
standard measurements of ventilatory ‘drive’ (calibrated
intraesophageal diaphragm electromyography, EMG),
ventilation (oronasal “ventilation”) and genioglossus
EMG activity. Drive withdrawal was determined by re­
viewing these measurements at the nadir drive (first
decile of drive with a stage). Pharyngeal physiology was
determined by examining collapsibility (reduced venti­
lation at eupneic drive) and responsiveness (ventilation-
drive slope). The mixed-model analysis compared REM
with NREM sleep; sensitivity analysis explored phasic
REM sleep.
Twenty-five patients exhibited REM sleep
(≥10 min). Compared with drive in NREM sleep, drive
in REM sleep dipped to noticeably lower nadir values
(-21.8% of eupnea; 95% CI: -31.2% to -12.4%;
P<.001), with an accompanying reduction in ventila­
tion (-25.8% of eupnea; 95% CI: -31.8% to -19.8%;
P<.001). However, no effect of REM sleep on collap­
sibility (ventilation at eupneic drive), baseline genio­
glossus EMG activity, or responsiveness was shown.
REM sleep was associated with greater OSA severity
(+10.1 events/hr; 95% CI: 1.8-19.8), but this associa­
tion vanished after adjusting for nadir drive (+4.3
events/hr; 95% CI: -4.2 to 14.6). Drive withdrawal was
exacerbated in phasic REM sleep. In patients with
OSA, the authors concluded that the pharyngeal
compromise characteristic of REM sleep seems to be
explained mainly by ventilatory drive withdrawal ra­
ther than preferential decrements in muscle activity or
responsiveness. Preventing drive withdrawal may be
the primary target for REM OSA.
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October 2023
Impaired UA sensation may lead to OSA patho­
physiology and could be a therapeutic target; the extent
of impaired sensation and its functional role in OSA
pathogenesis remains unclear. This systematic review
and meta-analysis sought to examine methods of UA
sensory testing in those with OSA, compare UA sen­
sation in participants with and without OSA, and ex­
plore the potential relationship between UA sensation
and OSA severity.352 Major electronic databases were
searched for studies that provided methods of UA sen­
sory testing in people with OSA (n + 3819). Thirty-eight
studies were selected, and information on the type of
sensation, testing methods, validity, and test-retest re­
liability data were extracted. Meta-analyses were per­
formed on case-controlled studies examining potential
relationships between UA sensation and OSA severity.
Seven categories of sensory testing were elucidated:
olfactory, gustatory, chemical, tactile, vibratory, thermal,
and perioral neuro-sensation. Testing methods varied
widely across studies; no tests were validated in OSA.
Individuals with OSA exhibited impaired UA sensation
to airflow (P<.001), chemical (P<.001), gustatory
(P=.009), olfactory (P=.04), tactile (P<.001), and vibratory
(P=.005) stimuli. UA sensory impairment increased with
disease severity (P<.001). The results suggest that, while
variable across testing methods, those with OSA have
impaired UA sensation, which is related to elevated
OSA severity. The development of valid and reliable UA
sensory testing methods that deal with UA function in
patients with OSA is warranted to inform future clinical
and research practices and elucidate potential ther­
apeutic targets.
It is difficult to discern which patients with OSA have
impaired driving ability, which may be explained by
decreased brain metabolite levels involved with mi­
tochondrial metabolism. This project examined markers
of brain energy metabolism in individuals with OSA
described as vulnerable or resistant to driving impair­
ment following extended wakefulness.353 Forty-four
participants with moderate-severe OSA underwent 28-
hour extended wakefulness with three 90-minute
driving simulation tests. Using a 2-step cluster analysis,
objective driving data (steering deviation and crashes)
from the second assessment (22.5 hrs. awake) was used
to categorize patients into vulnerable (poor driving,
n=21) or resistant groups (good driving, n=23). 1H
magnetic resonance spectra were gathered at baseline
using 2 scan sequences (short echo PRESS and longer
echo-time asymmetric PRESS or APRESS); key meta­
bolites were scrutinized, including creatine, glutamine,
and N-acetyl aspartate (NAA) in the hippocampus,
anterior cingulate cortex and left orbitofrontal cortex.
According to cluster analysis, the vulnerable group had
impaired driving performance compared with the re­
sistant group. It exhibited decreased levels of creatine
Cagna et al
503
(PRESS P=ns, APRESS P=.039), glutamate (PRESS
P<.01, APRESS P<.01), and NAA (PRESS P=.038,
APRESS P=.035) exclusively in the left orbitofrontal
cortex. With adjusted analysis, higher glutamate was
associated with a 21% (PRESS) and 36% (APRESS)
decreased risk of vulnerable classification. It was con­
cluded that brain mitochondrial bioenergetics in the
frontal brain regions are impaired in OSA patients vul­
nerable to driving impairment following sleep loss.
These findings suggest a potential method to identify an
at-risk OSA phenotype when evaluating fitness to drive,
but this requires additional, more extensive studies for
confirmation.
Leptin is a hormone related to satiety and has been
examined due to its association with obesity and OSA.
However, the distribution of leptin receptors in the
brainstem and the hypoglossal nucleus has yet to be
defined, even though associated muscle stimulation has
been studied in treating OSA. This study aimed to elu­
cidate the presence of leptin receptors in the nuclei of
these nerves to elucidate leptin involvement in stimu­
lating these areas.354 The brains of 5 cadavers were re­
moved during necropsy at the death verification service.
Informed consent was signed by a family member (wife,
mother, or child) who responded to a questionnaire
concerning comorbidities. Anthropometric data were
recorded. The medulla oblongata and pons were iden­
tified, and immunohistochemical staining analysis was
performed to identify the location of leptin receptors. In
the study, brown staining that signaled neurons was
seen as intense in the hypoglossal nerve nucleus,
moderate in the olivary nucleus, and mild in the dorsal
nucleus of the vagus nerve and the trigeminal nucleus.
More intense brown coloration was observed in the
nucleus and cytoplasm of the motor, as compared to
sensory neurons. The investigators concluded that the
immunoexpression of leptin receptor was shown in the
motor neurons of the human hypoglossal nucleus, and
these findings may assist in elucidating details of the
pathophysiology of neuromuscular control of airway
collapse during sleep and developing new pharma­
cotherapeutic agents to improve UA neuromuscular
tone in those with OSA.
Obstructive sleep apnea syndrome (OSAS) has been
defined by symptoms and ≥ 5 apneas per hour (AHI)
during PSG or ≥15 events/hr without symptoms. A re­
view explored a subgroup of patients: adult non-obese
individuals with OSA and their specific features.355 In
non-obese OSA patients (BMI <30 kg/m2), specific PSG
markers signify specific pathophysiological traits. Pre­
vious works identified an anatomical factor (such as
craniofacial features and retrognathia) in OSA non-
obese. The authors hypothesized that this subgroup
could have a non-anatomical pathological prevalent
trait. Little evidence supports the role of a low arousal
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threshold. This factor could explain the difficulty in
treating sleep apnea in non-obese patients and high­
lights the importance of a specific therapeutic approach
for each patient.
Increasing evidence has suggested that body water
content plays a crucial role in OSA; the causal re­
lationship has yet to be determined. This trial explored
whether greater whole-body water mass is causally as­
sociated with an elevated risk of sleep apnea employing
two-sample Mendelian randomization (MR) analysis.356
Body water mass (BWM)-associated genetic instruments
were isolated from a genome-wide association study by
Neale Lab, which incorporates 331 315 individuals of
European descent. Genetic variants for OSA were de­
rived from the FinnGen dataset. MR analysis was em­
ployed using inverse variance-weighted and weight
median methods, respectively. MR-Egger regression and
MR-Pleiotropy Residual Sum and Outlier tests were
performed to examine the directional pleiotropy.
Moreover, a multivariate MR analysis included BMI,
snoring, and waist-to-hip ratio as covariate exposures to
determine their confounding effects. To clarify the me­
chanisms of the association between BMW and OSA,
further MR analysis was performed on common ede­
matous diseases.
MR estimates demonstrated that per standard de­
viation increase in BWM led to an elevation in the risk of
sleep apnea by 49% (OR=1.490; 95% CI; 1.380-1.696;
P=1.75x10-9). After MR-Pleiotropy Residual Sum and
Outlier correction, the outcome further supports their
causal association (OR, 1.414; 95% CI: 1.253-1.595;
P=1.76x10-8). Furthermore, the multivariate MR analysis
exhibited a significant causal association between a
higher BWM and a higher risk of OSA (OR=1.204; 95%
CI: 1.031-1.377; P=.036). Genetic predisposition to a
higher BWM was also causally related to a greater risk of
edematous diseases. The findings suggested that in­
creased BWM is a potential risk factor for sleep apnea.
Pathologic edema is a possible intermediate factor
mediating this causal association.
OSA manifests significant endotypic traits, including
increased pharyngeal collapsibility, decreased dilator
muscle compensation, and higher chemoreflex loop
gain. This study explored how endotypic traits vary with
age, sex, and race/ethnicity to impact OSA disease se­
verity (AHI).357 These traits were estimated from PSG in
a diverse community-based cohort study (Multi-Ethnic
Study of Atherosclerosis or MESA, N=1971, age 54-93
years). Regression models examined associations be­
tween each exposure (continuous variables per 2 SD)
and endotypic traits (per SD) or AHI (events/hr), in­
dependent of other exposures. Generalizability was
evaluated in 2 independent cohorts. Higher AHI was
associated with obesity (+19 events/hr per 11 kg/m2
[2 SD]), male sex (+13 events/hr versus female), older
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age (+7 events/hr per 20 yrs), and Chinese ancestry (+5
events/hr versus White [obesity-adjusted]). Obesity-re­
lated elevation in AHI was best explained by increased
collapsibility (+.40 SD) and loop gain (+.38 SD; per­
centage mediated=26%; 95% CI: 20-32%). Male-related
increase in AHI was attributed to elevated collapsibility
(+.86 SD) and decreased compensation (-.40 SD; per­
centage mediated=57%; 95% CI: 50-66%). Age-related
AHI increase was explained by higher collapsibility
(+.37 SD) and greater loop gain (+.15 SD; percentage
mediated=48% 95% CI: 34-63%). Elevated AHI with
Chinese descent was explained by collapsibility
(+.57 SD; percentage mediated=87%; 95% CI: 57-
100%). Black race was associated with decreased col­
lapsibility (-.30 SD) and increased loop gain (+.29 SD).
Similar patterns were observed in the other cohorts. It
was concluded that different subgroups exhibit different
underlying pathophysiological routes to OSA, empha­
sizing the variability in mechanisms that could be tar­
geted for intervention.
The anatomic orientation of the epiglottis is such that
it points in the opposite direction to inspiratory airflow,
which may contribute to treatment difficulty with PAP
therapy in patients with epiglottic collapse. No previous
studies have examined PAP adherence in these in­
dividuals. This project explored adherence to auto-ti­
trating positive airway pressure (APAP) treatment in
those with epiglottic collapse.358 An age- and sex-mat­
ched case-control study was executed. Based on over­
night level 1 PSG, participants were prescribed APAP in a
tertiary hospital between July 2018 and March 2019. The
site of airway collapse was determined with drug-induced
sleep endoscopy (DISE). Demographic factors, sleep
questionnaire, PSG, and APAP usage data were analyzed.
Eighteen patients with epiglottic collapse (Epi-group) and
36 without (controls) were evaluated. It was determined
that 22.8% of patients in the Epi-group discontinued
APAP within 2 weeks, whereas only 2.8% of participants
in the Control group stopped APAP within 2 weeks
(P=.048). The percentage of days with >4 h of use was
significantly decreased in the Epi-group (64.6% versus
75.6%, P=.008). Furthermore, the adherence failure rate
was 66.7% in the Epi-group and 33.3% in the Control
group (P=.039). Patients with epiglottic collapse also ex­
hibited lower BMI, an unfavorable predictor of APAP
adherence. The results suggest that individuals with
epiglottic collapse have a greater APAP adherence failure
rate than patients without it; these individuals should be
closely followed during treatment, with alternate thera­
pies readily available.
Patients with OSA exhibit brain injury in sites con­
trolling autonomic, cognitive, and respiratory functions.
Brain alterations in sleep apnea may vary with disease
severity as measured by the AHI, which fails to provide
information about the apnea depth and length in
Cagna et al
October 2023
contrast to oxygen desaturation. Although significant
associations between brain injury and AHI in OSA are
recognized, whether AHI or the extent of oxygen de­
saturations better correlates with brain damage is un­
certain. This study used diffusion tensor imaging-based
measures to examine associations between brain al­
terations, AHI, and oxygen desaturation.359 Imaging
data were obtained from 19 patients with OSA em­
ploying a 3.0 Tesla MRI scanner and calculated, nor­
malized, and smoothed mean, axial, and radial
diffusivity maps used for correlations among brain
changes, oxygen desaturation, and AHI values. Positive
correlation and extent of injury (mean, axial, and radial
diffusivity values) and AHI occurred in the frontal areas,
cingulate and insula, amygdala, hippocampus, and basal
pons; negative correlations manifested in the putamen,
internal-capsule, globus-pallidus, and cerebellar cor­
tices. Regional diffusivity values and oxygen desatura­
tion demonstrated positive correlations in the cingulate,
frontal, putamen, and cerebellar sites and negative in­
teractions in several areas, including the occipital index.
It was concluded that patients with OSA demonstrate
negative and positive correlations, indicated by elevated
and reduced diffusivity values, resulting from chronic
and acute alterations in those areas. The extent of injury
in OSA somewhat depends on the extent of AHI and
oxygen desaturation, with the effects representing the
continued progression from acute to chronic processes.
There are conflicting results on the association be­
tween OSA and periodontitis; a systematic review and
meta-analysis set out to clarify the relationship between
the two and determine if periodontitis is associated with
sleep apnea disease severity.360 Electronic databases, in­
cluding Embase, PubMed, Scopus, and Web of Science,
from inception to December 31, 2021, using a combina­
tion of applicable keywords without language restriction.
Observational studies enlisting adults (≥18 years old) that
examined the association between periodontitis and OSA
were included. Two investigators independently reviewed
the titles and abstracts of identified articles for potential
suitability. The prevalence of periodontitis was compared
between OSA-positive and negative participants em­
ploying a pooled odds ratio (OR) with 95% CI. The I2
statistic explored the heterogeneity among the studies. Of
265 citations, 10 eligible studies involving 30 994 partici­
pants were ultimately selected. The study analysis de­
monstrated a significant association between periodontitis
and OSA (OR=2.17, 95% CI: 1.66-2.83), with no sig­
nificant heterogeneity among the studies (I2=42.7%,
P=.073). Analysis of 3 surveys demonstrated that period­
ontitis is significantly associated with mild-moderate OSA
(OR=2.51, 95% CI: 1.32-4.78; I2=0.0%, P=.527) but not
with severe OSA (OR=1.58, 95% CI: .07-3.58; I2=0.0%,
P=.469). Based on the results, periodontitis is directly as­
sociated with OSA; periodontitis is associated with mild-
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505
moderate sleep apnea but not with severe OSA. Further
studies are called for to clarify the mechanisms of these
associations.
In 2010, the American Heart Association (AHA) de­
fined a novel construct of cardiovascular (CV) health to
promote a paradigm change from emphasizing disease
treatment to one inclusive of positive health promotion
and preservation across life in populations and in­
dividuals. Extensive subsequent evidence has supplied
insights into the original approach's strengths and
weaknesses to define and quantify CV health. In re­
sponse, the AHA initiated a writing group to recommend
enhancements and updates.361 The definition and
quantification of each original parameter (Life’s Simple 7)
were scrutinized for responsiveness to interindividual
variation and change. New metrics were considered, and
the age spectrum was expanded to involve the entire life
course. The foundational contexts of social determinants
of physical and psychological health were addressed as
critical factors in optimizing and preserving CV health.
This presidential advisory introduced an upgraded ap­
proach to evaluating CV health: Life’s Essential 8. The
components of Essential 8 include diet (updated); phy­
sical activity; nicotine exposure (updated); sleep health
(new); BMI; blood lipids (updated); blood glucose (up­
dated); and blood pressure. Each metric has a new
scoring algorithm ranging from 0 to 100 points, allowing
the calculation of a new composite CV health score (the
unweighted average of all components that also varies
from 0 to 100 points. Methods for implementing CV
health assessment and longitudinal monitoring are dis­
cussed, as are possible data sources and tools to promote
widespread adoption in policy, public health, clinical,
institutional, and community settings.
OSA elevates sympathetic vasoconstrictor drive and
decreases baroreflex sensitivity (BRS), the amount to
which BP changes modify the cardiac output. Whether
nocturnal CPAP corrects BRS following OSA is unknown.
This cross-sectional study evaluated spontaneous BRS
using non-invasive continuous BP and ECG measure­
ments at rest and during handgrip and Valsalva chal­
lenges, maneuvers that increase vasoconstrictor drive
with progressively greater BP, in untreated OSA
(unOSA), CPAP-treated OSA (cpOSA) and healthy
(CON) participants.362 The total sample was 104 in­
dividuals, including 34 unOSA (22 male; age 50.6 ±14.1
years; REI 21.0 ±15.3 events/hr), 31 cpOSA (22 male; age
49.6 ±14.5 years; REI 23.0 ±14.2 events/hr; self-report 4+
hrs/night, 5+ days/week, 6 months), and 39 CON (17
male; age 42.2 ±15.0 years). BRS was recorded, and BP
variability (BPV) was correlated with BRS during the
maneuvers. BRS in unOSA, cpOSA, and CON was, re­
spectively (mean ±SDv in ms/mmHg), at rest 14.8 ±11.8,
15.8 ±17.0, and 16.1 ±11.3; during handgrip 13.3 ±7.6,
12.7 ±8.4, and 16.4 ±8.7; and during Valsalva 12.7 ±8.0,
THE JOURNAL OF PROSTHETIC DENTISTRY
506
11.5 ±6.6, and 15.1 ±8.9. BRS was lower in cpOSA than
CON for handgrip (P=.04) and Valsalva (P=.03). BRS was
negatively correlated with BPV in unOSA during Valsalva
and handgrip for cpOSA (both R=-.4, P=.02). BRS was
found to be negatively correlated with OSA severity, from
none to severe (R=-.02, P=.04, n=104). The investigators
concluded that BRS was reduced, BPV elevated in OSA
during the pressure challenges, and disease severity ne­
gatively correlated with BRS, which was expected. This
cross-sectional study demonstrated that both CPAP-
treated (self-report) and untreated OSA exhibited de­
creased BRS, leaving open whether within-person CPAP
improves BRS.
The mechanism linking OSA with regulating in­
flammatory response must be better defined. This project
sought to elucidate inflammasome activation, mainly of
NLRP3 (nucleotide-binding oligomerization domain-like
receptor 3), in patients with severe OSA.363 NLRP3 ac­
tivity was examined, as well as essential components of
the inflammasome cascade (including adaptor molecule
apoptosis-associated speck-like protein, caspase-1, Gas­
dermin D, IL-1β, IL-18, and tissue factor) in monocytes
and plasma from patients with severe OSA and control
participants without sleep apnea. The association of the
different key markers with inflammatory comorbidities
was analyzed. Monocytes from individuals with severe
sleep apnea demonstrated greater NLRP3 activity than
those from controls, which directly correlated with the
AHI and hypoxemic indices. NLRP3 overactivity activated
inflammatory cytokines (IL-1β and IL-18) via caspase-1
and increased Gasdermin D, releasing tissue factor. In
vitro models verified that monocytes increase NLRP3
signaling with intermittent hypoxia (IH) in a hypoxia-
inducible factor-1α-dependent fashion and in concert
with plasma from patients with OSA. Plasma con­
centrations of tissue factor were greater in patients with
OSA with systemic inflammatory comorbidities than in
those without them. It was noted that in severe OSA,
NLRP3 activation might be a linking mechanism between
IH and other OSA-induced immediate alterations with
the development of systemic inflammatory response.
Another cross-sectional study aimed to examine the
clinical and PSG characteristics of OSA patients with
hypertension (HTN) and explore the sex differences in
the relationship between REM OSA and HTN.364 A total
of 808 individuals diagnosed with OSA at a tertiary
hospital were enlisted in this trial and were divided into
groups presenting with or without HTN. The clinical and
polysomnographic characteristics were assessed be­
tween the groups. A multivariate binary logistic analysis
evaluated the association between REM OSA and hy­
pertension. After adjustment for confounding variables,
the risk of HTN in patients with OSA increased with
severity categories of AHI during REM sleep (REM AHI)
(OR=1.61 for REM AHI ≥58.87 events/hr relative to REM
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Volume 130 Issue 4
AHI <30.50 events/hr, 95% CI 1.07-2.42, P=.022).
Consistent with these findings, when taken as a con­
tinuous variable, this association remained significant
(OR=1.007, 95% CI 1.001-1.014, P<.05). This effect was
more pronounced in women; OR for REM AHI ≥57.24
events/hr relative to REM AHI <0.36 events/hr was 2.79
(95% CI 1.16-6.73; P=.022). No significant difference
was appreciated in male patients. The investigators
concluded that REM AHI was significantly and posi­
tively associated with HTN in those with OSA, and the
effect was greater in female patients.
The evidence for an association between cancer sur­
vival and OSA remains underexplored. A large retro­
spective multicenter clinical cohort study attempted to
explore an association between markers of OSA severity
(respiratory disturbances, hypoxemia, and sleep frag­
mentation) and cancer-related mortality in patients with
previously diagnosed cancer.365 Linked clinical and pro­
vincial health administrative data were gathered on
consecutive adults who underwent a diagnostic PSG
between 1994 and 2017 in 4 Canadian academic hospitals
and were previously diagnosed with cancer via the On­
tario Cancer Registry. Multivariate cause-specific Cox
regressions were performed to address the research ob­
jective. The sample included 2222 individuals. Over a
median follow-up time of 5.6 years (IQR 2.7-9.1 yrs), 261
of 2222 (11.7%) patients with prevalent cancer died from
cancer-related causes, which accounted for 44.2% (261/
590) all-cause deaths. Controlling for age, sex, alcohol use
disorder, prior heart failure, chronic obstructive pul­
monary disease, HTN, diabetes, treatment for OSA, clinic
site, year of the PSG and time since the cancer diagnosis,
measures of hypoxemia and sleep fragmentation, but not
AHI, were significantly associated with the cancer-spe­
cific mortality; percentage of time spent with arterial
oxygen saturation (SaO2),90% (HR per 5% increase=1.05;
95% CI: 1.01-1.09); mean SaO2 (HR per 3% increase=.79;
95% CI: .68-.902); and percentage of stage 1 sleep (HR
per 16% increase=1.27; 95% CI: 1.02-1.51). The in­
vestigators concluded that in this large clinical cohort of
adults with suspected OSA and previously diagnosed
cancer, nocturnal hypoxemia, and sleep fragmentation as
markers of OSA severity were significantly associated
with cancer-related mortality, highlighting the need for
more targeted risk awareness.
OSA is a significant risk factor for cardiovascular
disease (CVD) development. This project sought to
create and investigate a machine-learning approach
with features for evaluating the 10-year CVD mortality
risk of those with OSA.366 Participants included 2464
patients with OSA who satisfied the inclusion criteria
selected from the Sleep Heart Health Study. They ex­
amined the importance of potential features by mutual
information. The top 9 features were chosen to develop
a random forest model. The model performance was
Cagna et al
October 2023
evaluated on a test set (n=493) using the area under the
receiver operating curve (ROC) with 95% CI and con­
fusion matrix. A random forest model assigned the
highest area under ROC of .84 (95% CI: .78-.89). The
specificity was 73.94%, and sensitivity 81.82%. Sixty-
three years old was a threshold for elevated risk of 10-yr
CVD mortality. Individuals with severe OSA exhibited
greater risk than those with mild disease. The in­
vestigators concluded that a random forest model could
quickly assess the risk of 10-yr CVD mortality. Their
model may help educate patients with OSA in evalu­
ating their future risk of CVD mortality.
Previous investigations of systematic reviews with
meta-analyses have shown that OSA is correlated
with multiple health outcomes. This umbrella review
evaluated the available evidence for the associations
between OSA and health outcomes.367 A meta-ana­
lysis of prior observational studies that reported as­
sociations between OSA and health outcomes in all
human populations and settings was conducted; these
studies were used to conduct an umbrella review of
available systematic reviews and meta-analyses. Sixty-
six studies consisting of 136 unique outcomes were
selected for this analysis. Of those outcomes, 111 had
significant associations (P<.05). Only 7 outcomes ex­
hibited a high quality of evidence (coronary re­
vascularization after percutaneous coronary
intervention or PCI; postoperative respiratory failure;
steatosis; alanine transaminase or ALT elevation;
metabolic syndrome or MS; psoriasis; and Parkinson’s
disease or PD). Twenty-four outcomes had a moderate
quality of evidence, and the remaining 80 had poor
quality. Sixty-nine outcomes demonstrated significant
heterogeneity; 25 outcomes exhibited publication bias.
Sixty-three (95%) studies showed critically low
methodological quality. The reviewers concluded that
out of 66 meta-analyses evaluating 136 unique out­
comes, only 7 were statistically significantly high-
quality evidence. OSA may correlate with an elevated
risk of coronary revascularization after PCI, post­
operative respiratory failure, steatosis, ALT elevation,
MS, psoriasis, and PD.
Strong clinical and epidemiological evidence supports
the importance of genetic factors influencing sleep apnea;
however, data implicating specific genes are scarce. This
study sought to elucidate rare variants contributing to
OSA severity.368 High-detail genomic sequencing data
from the NHLBI Trans-Omics for Precision Medicine
(TOPMed) program and imputed genotype data from
multiple population-based studies were involved in
linkage analysis in the CFS (Cleveland Family Study),
followed by multistage gene-based association analyses
in independent cohorts for AHI. A total of 7708 partici­
pants of European descent were included. Linkage in the
CFS elucidated a suggestive linkage peak on
Cagna et al
507
chromosome 7q31 (LOD=2.31). After accounting for
multiple comparisons, the gene-based analysis identified
21 rare noncoding variants in Caveolin-1 (CAV1) asso­
ciated with lower AHI (P=7.4x10-8). These noncoding
variants significantly supported the linkage evidence
(P<.001). Follow-up analysis elucidated significant asso­
ciations between these variants and elevated CAV1 ex­
pression, and greater CAV1 expression in peripheral
monocytes was linked with lower AHI (P=.024) and
higher minimum overnight oxygen saturation (P=.007). It
was concluded that rare variants in CAV1, a membrane-
scaffolding protein integral to multiple cellular and me­
tabolic functions, are associated with greater CAV1 gene
expression and lower OSA severity, suggesting a novel
target for impacting OSA severity.
Sleep bruxism and Temporomandibular
Disorders (TMDs)
A scoping review examined the evidence on the pre­
sumed relationships between sleep bruxism (SB) and
OSA to evaluate the extent of research on this topic and
generate future research topics.369 A review involving
studies examining temporal and overall association and
prevalence of SB and OSA was conducted. Six databases
and nonpeer-reviewed literature were searched; studies
selection involved 3 independent reviewers. A narrative
synthesis of the findings was performed. Thirteen studies
in adults and 8 involving children were ultimately se­
lected. The median of concomitant conditions prevalence
is 39.3% in adults and 26.1% in children. Substantial
methodological variability was identified among adult
studies and even more when detection methods were
compared in children. No significant association between
OSA and SB surfaced in most adult studies, while a
possible association emerged in children. The reviewers
concluded that based on the existing literature, it is not
possible to verify that there is a relationship between SB
and OSA in adults. The association seems plausible in
pediatric patients, but existing evidence is lacking. Stan­
dardized validated methodologies for identifying SB
should be consistently used in children and adults before
attaining any conclusion regarding an association.
Moreover, assessment of shared phenotypes between
individuals with SB and those with OSA may reveal new
insights that will promote personalized approaches to
optimize the management of such comorbidities.
Sleep bruxism is a condition regulated centrally, with
multifactorial etiology; it can occur due to medication use
and certain systemic disorders. A cross-sectional study
aimed to elucidate associations between SB, obstructive
sleep apnea-hypopnea syndrome (OSAHS), and the use
of antidepressants.370 Two-hundred forty participants
underwent PSG for medical reasons. Patients’ self-re­
ported medical histories were gathered to collect data
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508
about general health conditions and the use of anti­
depressant medications. PSG was used to assess sleep
data and respiratory events and determine the AHI. SB
was also evaluated via PSG electrodes on the masseter
muscles and chin. SB was defined by >2 events of
rhythmic masticatory muscle activity (RMMA) per hour of
sleep. Statistical analyses were conducted to compare the
presence of SB and AHI and the use of antidepressants.
Statistically significant differences were found between
bruxers and non-bruxers when evaluating AHI
(48.28 ±25.84; P=.001) and severity of OSAHS (P=.015).
Correlations did not exist between the use of anti­
depressants and bruxism with comparative analyses
(P=.072); logistic regression did suggest that these medi­
cations may represent greater odds for SB development
(OR=2.387; P=.005). The investigators concluded that the
relationship between antidepressant use and SB remains
inconclusive. SB is associated with OSAHS, mainly in
severe form. Identifying SB may elevate suspicion of
concomitant systemic disturbances.
Systematic reviews on SB as a comorbid condition of
other sleep-related disorders are sparse; such works
would contribute to the insight of sleep clinicians into the
occurrence of SB in patients with other sleep-related
conditions and the underlying mechanisms of such co­
morbidities. This systematic review sought to elucidate
the prevalence of SB in adults with other sleep-related
disorders, determine the associations between SB and
other sleep-related disorders, and explain the underlying
mechanisms of these interactions.371 A search was con­
ducted on SB and sleep-related disorders in PubMed,
Embase, Cochrane Library, and Web of Science to iden­
tify studies published until May 2020. Quality assessment
was performed using the Risk of Bias Assessment tool for
Non-randomized Studies. Of the 1539 unique selected
studies, 37 papers were involved in the systematic review.
The prevalence of SB in adults with OSA, restless leg
syndrome, periodic limb movement during sleep, sleep-
related gastroesophageal reflux disease, REM behavior
disorder (RBD), and sleep-related epilepsy was greater
than in the general population. However, the specific
mechanisms underlying these positive associations could
not be elucidated. The reviewers concluded that SB is
more prevalent in individuals with the previously listed
sleep disorders than in the general population. Sleep
arousal may be a common factor associated with all the
designated disorders except RBD and PD. The associa­
tions between SB and these identified sleep-related dis­
orders warrant more SB screening in patients with these
sleep conditions.
Sleep bruxism is characterized by rhythmic mastica­
tory muscle activity. This project set out to clarify the
number and type of jaw muscles necessary for a valid
RMMA scoring in patients with OSA.372 Ten individuals
with OSA (4 men; age 50.1 ±8.1 yrs) participated.
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RMMA was scored using ≥ 1 of the following jaw
muscles’ EMG traces of PSG recordings: bilateral
masseter and temporalis (4MT; the reference standard);
unilateral masseter (1 M); bilateral masseter (2 M);
unilateral temporalis (1 T); bilateral temporalis (2 T);
unilateral chin EMG (1 C); and bilateral chin EMG (2 C).
1 M, 2 M, 1 T, and 2 T exhibited excellent agreement
with 4MT (intraclass correlation coefficient=.751, .976,
.815, and .950, respectively), while 1 C and 2 C pre­
sented fair agreement (intraclass correlation coeffi­
cient=.662 and.657). Furthermore, 2 M and 2 T
demonstrated good sensitivity (87.8% and 72.0%) and
positive predictive value (83.1% and 76.0%). In contrast,
1 M and 1 T had good sensitivity (88.4% and 87.8%) and
a fair positive predictive value (60.1% and 53.2%). Ad­
ditionally, 1 C and 2 C showed poor sensitivity (41.1%
and 40.3%) and decent positive predictive value (62.9%
and 60.6%). Therefore, it was concluded that PSG with
bilateral masseter or temporalis EMG recording is con­
sidered valid in RMMA scoring in patients with OSA. In
contrast, the unilateral masseter or temporalis muscle
EMG exhibited only fair accuracy, and chin EMG had
poor accuracy. As a result, these montages cannot be
recommended for RMMA scoring in the presence
of OSA.
A network analysis examined the association be­
tween self-reported SB and insomnia and their potential
risk factors (such as depression and anxiety) and created
a network model with all these factors.373 The Nether­
lands Sleep Registry provided 2251 participants, who all
completed questionnaires on self-reported SB, in­
somnia, depression, anxiety, smoking frequency, al­
cohol, and caffeine use. The associations between self-
reported SB and other variables were analyzed via uni­
variate analysis, multivariate logistic regression, and
network analysis. Although univariate analysis demon­
strated that there was a positive association between SB
and insomnia (P<.001), this association disappeared in
the multivariate logistic regression model (P=.258).
However, multivariate logistic regression did show an
association between self-reported SB and anxiety
(OR=1.087; 95% CI: 1.041-1.134). The network model
showed no direct link between self-reported SB and
insomnia; however, there was an indirect link between
the 2 via anxiety. The authors noted that although self-
reported SB has no direct association with insomnia,
anxiety is a linking factor between them.
Reliable and sustainable bruxism evaluation would
be ideal, but existing studies present mixed results. This
study sought to establish the agreement between patient
self-reports and clinical signs of SB with EMG and
electrocardiographic (ECG) data.374 Two hundred par­
ticipants from a German dental clinic population (120
women, 80 men) participated in the protocol. In­
dividuals completed different SB questionnaires, had a
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October 2023
clinical examination to evaluate bruxism signs, and used
the Bruxoff device to record EMG/ECG data for 5 nights.
To assess interrater reliability for clinical diagnosis of
bruxism, 126 participants were examined for clinical
signs by 2 independent uncalibrated operators. Statis­
tical evaluation included sensitivity, specificity, and ac­
curacy calculations of Cohen’s kappa. According to the
Bruxoff results, 106 individuals were described as
bruxers (94 non-bruxers). The 106 were further classified
into 47 moderate and 59 intense bruxers. The greatest
accuracy and sensitivity values were recorded for the
overall score for clinical bruxism signs (accuracy: 72.0%;
sensitivity: 70.8%). The best specificity (96.8%) was ex­
hibited for the question regarding tooth grinding in the
last 2 weeks reported by others, but concurrent sensi­
tivity was very low (3.8%). Interrater reliability analysis
demonstrated a subsequent agreement (Cohen kappa
of.6). The results indicate that self-report questionnaires
and clinical signs have moderate sensitivity, specificity,
and accuracy for diagnosing bruxism compared with an
ambulatory device to detect SB (Bruxoff). Substantial
agreement was found between the 2 examiners for
clinical signs of bruxism.
Another project examined the association of sleep
bruxism activity with smartphone addiction and sleep
quality among university students during the COVID-19
pandemic.375 A cross-sectional online survey concerning
social distancing involving 546 university students was
conducted from May 29 to June 2, 2020. The participants
were undergraduate and graduate students in Brazilian
public and private universities. A questionnaire self-re­
ported sociodemographic information, academic data, and
severity of possible sleep bruxism (PSB) activities
(grinding, bracing, and thrusting). Participants answered
the Brazilian version of the Pittsburgh sleep quality index
(PSQI-BR) and the smartphone addiction scale (SAS-SV)
short form. Descriptive statistics and multivariate logistic
regression were performed (P=.05). Sample average age
was 24.9 ±5.5 years. Students with higher scores of PSQI-
BR were more likely to present severe PSB-bracing
(OR=1.154; 95% CI: 1.057-1.260), severe PSB-grinding
(OR=1.133; 95% CI: 1.048-1.225) and severe PSB-
thrusting (OR=3.193; 95% CI: 1.107-1.294). Those with
children demonstrated a 3 times greater chance
(OR=3.193; 95% CI: 1.236-8.250) of reporting severe PSB-
thrusting. Being female elevated the chance of reporting
moderate (OR=3.315; 95% CI: 1.333-8.914) and severe
(OR=2.940; 95% CI: 1.116-7.747) PSB-thrusting. Partici­
pants not enrolled in remote learning exhibited a 2 times
greater chance (OR=2.638; 95% CI: 1.233-5.649) of re­
porting moderate PSB-grinding. Students with higher
scores in SAS-SV had a slight increase in the chance of
exhibiting mild (OR=1.042; 95% CI: 1.009-1.077) and
moderate (OR=1.065; 95% CI: 1.018-1.115) PSB-bracing,
as well as mild (OR=1.044; 95% CI: 1.011-1.078) and
Cagna et al
509
moderate (OR=1.041; 95% CI: 1.005-1.077) PSB-
thrusting. It was concluded that smartphone addiction,
poor sleep quality, having children, female sex, and in-
person learning were associated with possible SB during
the COVID-19 pandemic.
Various biofeedback stimulation methods of mana­
ging SB have recently emerged; the outcome of successive
applications of vibratory feedback stimulation has yet to
be elucidated. This prospective, single-arm, open-label
intervention study explored the effect of vibration feed­
back stimulation via an oral appliance (OA) on SB over
the course of 4 weeks of intervention.376 Ten participants
diagnosed with “definite” SB used a specially designed
OA for 45 nights at home. A force-based SB detection
system using a pressure-sensitive piezoelectric film
placed internally in the appliance triggered a vibrator
attached to the OA. Vibratory stimulation was withheld
during the initial 2-week adaptation period (first to fif­
teenth nights), applied during the 4-week stimulation
phase (sixteenth to forty-third nights), and again with­
held during the post-stimulation period (nights 44 and
45). The number and duration of SB episodes/hour of
sleep were calculated based on masseter EMG recordings
via in-home portable PSG and compared between the
fifteenth and forty-fifth nights (without stimulation) and
the seventeenth and forty-third nights (with stimulation).
The number and duration of SB episodes significantly
dropped after vibratory stimulation (fifteenth versus se­
venteeth nights: P=.012 and P=.012, respectively), then
significantly increased with cessation of vibration after the
stimulation period (forty-third versus forty-fifth nights:
P=.023 and P=.023, respectively). The investigators con­
cluded that contingent vibratory stimulation via an OA
might continuously suppress SB-related masticatory
muscle activity for 4 weeks and may be an effective option
for SB management.
OSA is associated with elevations in QT interval
corrected for heart rate (QTc interval) and QT variability
index (QTVI), and sleep bruxism is prevalent in patients
with OSA. A pilot study explored whether QTc interval
and QT variability were altered during episodes of
RMMAs in SB patients with and without OSA.377 The
RR and QTc intervals and QTVI during RMMAs with or
without accompanied limb movements (RMMAs/LMs)
in 10 controls and 10 patients without OSA and during
apneic and recovery periods of OSA in 10 SB patients
with OSA were evaluated. In those with SB without
OSA and control participants, QTc intervals and QTVI
were significantly elevated during RMMAs/LMs com­
pared with those during the 10-second periods (from the
tenth to the twentieth second) before the onset and
following the offset of RMMAs/LMs and significantly
increased during RMMAs/LMs with awakenings com­
pared with those with microarousals and no arousals.
Furthermore, QTc interval and QTVI were positively
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510
correlated with the duration of RMMAs/LMs. In addi­
tion, in the SB patients with OSA, QTc interval and
QTVI during the recovery period of OSA events were
significantly more prolonged and more significant than
those during the apneic period regardless of accom­
panied RMMAs/LMs. QTc interval and QTVI during the
apneic and recovery periods accompanied by RMMAs/
LMs were significantly more prolonged and higher than
those without accompanied RMMAs/LMs. The authors
concluded that OSA and RMMAs/LMs events were as­
sociated with longer QTc intervals and greater QTVI.
The authors suggested that RMMAs/LMs might con­
tribute to these alterations associated with OSA events
accompanied by RMMAs/LMs.
Sleep bruxism is recognized as a complex behavior
with a possible association with the serotonergic pathway.
An exploratory study sought to examine serotonin (ST)
levels in participants with SB diagnosed via video PSG
and assess whether those levels were associated with BMI,
heart rate (HR), and sleep parameters.378 Participants
were hospitalized adults in the Department and Clinic of
Internal Medicine, Occupational Diseases, Hypertension,
and Clinical Oncology at the Wroclaw Medical University.
Single-night video PSG measured sleep, SB parameters,
and HR; BMI and blood ST values were also determined.
A total of 105 individuals were enrolled (80 women). All
participants were Whites aged 18 to 63 (mean age
33.43 ±10.8). Seventy-five patients (71.4%) exhibited SB
(bruxism episode index or BEI ≥2), and 30 (28.57%) did
not. Fifty individuals (47.62%) had severe SB (BEI ≥4). The
results showed reduced blood ST levels were associated
with severe SB, higher BEI, REM sleep and BMI, and
lower maximal pulse. It was concluded that severe SB and
associated phenomena co-occur with lower blood ST
concentration, which supports the hypothesis on the re­
lationship between the ST pathway and SB.
Another study hypothesized that individuals with
primary SB demonstrate masseter and cortical hyper­
activities during quiet sleep intervals associated with a
high frequency of RMMA.379 Fifteen SB patients and 10
controls underwent PSG. The frequencies of oromotor
events and arousals and the percentage of arousals with
oromotor events were assessed. Masseter muscle tone
during sleep was defined using a cluster analysis. EEG
power and heart rate variability (HRV) were quantified
and compared between the 2 groups and among sleep
stages. The frequency of RMMA and percentage of
arousals with RMMA were significantly greater in those
with SB compared to controls in all stages. At the same
time, the variables for nonrhythmic oromotor events did
not differ significantly between the groups. In patients
with SB, the frequency of RMMA was the highest in N1
and the lowest in N3 and REM, while the percentage of
arousals with RMMA was greater in N3 than in stages
N1 and REM. The cluster analysis classified masseter
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Volume 130 Issue 4
activity during sleep into 2 clusters for masseter tone and
contractions. Masseter muscle tone demonstrated ty­
pical stage-dependent alterations in both groups but did
not significantly differ between the groups. Moreover,
no significant differences were found in EEG power or
HRV between the groups. The investigators concluded
that young individuals with SB showed sleep stage-de­
pendent increases in the responsiveness of RMMA to
transient arousals but not masseter or cortical hyper­
activity during sleep.
TMD encompasses complaints of pain in the TMJs,
fatigue, pain of craniocervical muscles, mandibular
movement limitation, and TMJ noises. SB involves
rhythmic (phasic) or non-rhythmic (tonic) masticatory
muscle activity during sleep and is not a movement or
sleep disorder in otherwise healthy individuals. This
case-control study set out to affirm or reject the null
hypothesis that there is no association between SB and
TMD.380 Participants were recruited from patients of the
Artmedica Clinic, Mossoro City, Rio Grande do Norte,
Brazil. Based on inclusion and exclusion criteria, in­
dividuals who underwent PSG were invited to partici­
pate. The sample included 40 participants (age 19
to 76 yrs); they were administered the questionnaire of
the European Academy of Craniomandibular Disorders
(AEDC). Those who answered yes to ≥ 1 question were
referred to the primary investigator’s dental clinic for
examination. Those who satisfied the Diagnostic Criteria
for TMDs (DC/TMD) were examined, and their condi­
tion was classified into ≥ 1 subtype of TMD. The parti­
cipants were assigned into 4 groups based on PSG
results and the responses to the AEDC questionnaire. Of
the 40 patients who answered the questions and un­
derwent PSG, 28 exhibited TMD symptoms. The data
were described as simple frequency and percentage
values using a statistical software program. Values of
P<.05 were considered significant.
The results demonstrated that the frequency of TMD
in those diagnosed with SB was 46.4%. Based on the
DC/TMD of the 28 individuals, local myalgia was the
most prevalent TMD subtype (85.7%). Of the total
sample, 32.5% had TMD and SB, 36.4% were men, and
31 to 40 years old (40%). Therefore, it was concluded
that there was no association between SB as currently
defined and TMD in this cohort, confirming previous
findings on this topic.
Studies on TMD severity in patient populations are
rare; this project compared the psychological states and
OHRQoL among individuals with varying TMD se­
verity.381 Adults ≥ 18 years with and without (controls)
TMDs were enrolled from the TMD/oro-facial pain center
and prosthodontics department, respectively. The pre­
sence and severity of TMDs were determined with the
Fonseca Anamnestic Index (FAI), and TMD diagnoses
were confirmed with the DC/TMD. Psychological states
Cagna et al
October 2023
and OHRQoL were explored with the Depression, An­
xiety, Stress Scales-21 (DASS-21), and Oral Health Im­
pact Profile for TMDs (OHIP-TMD). Data underwent
chi-squared, Kruskal-Wallis/Mann-Whitney U tests, and
the Spearman correlation (α=.05). A total of 961 partici­
pants with a mean age of 32.99 ±13.14 yrs (71.19%
women) were evaluated. Frequencies of the various TMD
categories were as follows: no TMD/controls (12.07%),
mild TMD (24.56%), moderate TMD (40.37%), and se­
vere TMD (23.00%). The 3 most common TMD-related
symptoms were TMJ noises, mouth-opening limitation,
and muscle pain. Those with moderate/severe TMD ex­
hibited more intra-articular and combined disorders.
They reported significantly greater levels of depression,
anxiety, stress, and poorer OHRQoL than those with no/
mild TMD (P<.001). Moderate-to-strong correlations
were noted between FAI and DASS-21/OHIP-TMD
scores (rs=.42-.72). The investigators concluded that pa­
tients with moderate/severe TMD had significantly
greater levels of psychological disturbance and worse
OHRQoL, as these two are correlated, psychological
well-being must be considered when managing those
with moderate/severe TMDs.
The evidence on the relationship between anxiety
and depression and individuals with distinct subtypes of
TMD is uncertain, and an extensive review on the topic
is missing. A systematic review and meta-analysis ex­
plored the distribution and severity of anxiety and de­
pression in those diagnosed with different TMD
subtypes.382 This project is registered in PROSPERO
(CRD42020150562) and follows the PRISMA 2020
Statement. Databases searched included PubMed, Web
of Science, Scopus, and SciELO (up to March 12, 2021)
and the references from each study. Inclusion criteria
consisted of patients diagnosed with TMD using the
Research Diagnostic Criteria (RDC/TMD) or DC/TMD
instruments; evaluation of anxiety and depression with
validated psychological instruments; and allocation of
participants into a minimum of ≥ 2 distinct subtypes
with at least 1 group exhibiting myofascial pain (com­
parison group). Analyses were performed using the
RevMan 5.3.5 statistical software program and random-
or fixed-effects models (α=.05). The quality of evidence
was evaluated based on the review authors’ discretion
based on a 10-item appraisal tool for prevalence studies
and with the Newcastle-Ottawa scale.
Of the 4086 records identified, 24 were eligible for
inclusion; meta-analyses were performed with 20 stu­
dies. In total, 3678 participants were involved in the
review. Most studies found that individuals with myo­
fascial pain exhibited similar occurrence and severity of
anxiety/depression compared to other subtypes of TMD.
However, the average prevalence seemed greater among
myofascial pain (muscular TMD) patients. Despite
moderate-high heterogeneity, anxiety and depression
Cagna et al
511
were more often distributed among patients with myo­
fascial pain (P=.001). TMD patients without myofascial
pain showed less severe levels of anxiety and depression
than individuals with only myofascial pain (P ≤ .01). The
type of psychological instrument appears to impact the
assessment of both anxiety and depression emotional
states. The reviewers concluded that results suggest that
patients with myofascial pain are more anxious and
depressed than those with other subtypes of TMD. They
note that a proper evaluation of the psychological state
of patients appears to be critical to devising adequate
treatment and management of each subtype of TMD.
TMD is a disabling facial pain syndrome with a high
prevalence of insomnia that mainly impacts women.
Insomnia with objective short sleep duration (ISSD) is
an emerging phenotype linked to cardiometabolic
morbidity and greater mortality. This study explores the
association of ISSD with clinical and laboratory pain and
systemic inflammation in TMD.383 Baseline data were
gathered from 128 women with TMD and insomnia in a
clinical trial examining psychological interventions for
sleep and pain. Participants completed self-report
questionnaires, 1-night PSG, a 2-week actigraphy as­
sessment, quantitative sensory testing (QST) to examine
cold pain tolerance, pain sensitivity and central sensiti­
zation, and circulating interleukin (IL)-6 levels were
determined to assess systemic inflammation. Thirty-one
individuals (24.2%) satisfied the criteria for ISSD [PSG
(sleep duration <6 h)]. Compared with those with in­
somnia and normal sleep duration, ISSD were older
(40.4 versus 34.9, P<.05), and a greater proportion self-
identified as Black (48.4% versus 11.3%, P<.001). Mul­
tivariate regression analysis showed that ISSD endorsed
greater self-report pain severity and functional limitation
of the jaw. ISSD also showed elevated generalized pain
sensitivity, enhanced central sensitization, cold pressor
tolerance, and higher resting IL-6 concentrations. The
investigators noted that this is the first study to describe
the ISSD phenotype in a chronic pain sample and ex­
pand the scope of its adverse health outcomes to chronic
pain. ISSD may be an essential chronic pain phenotype
associated with a more severe clinical and laboratory
pain profile, and future research should explore im­
plications for treatment response and disease trajectory.
Coronavirus-19 disease and sleep issues
The COVID-19 pandemic has been associated with re­
duced sleep quality and psychological distress, and the
general population has responded to the pandemic and
quarantine orders in multiple ways. This cross-sectional
study explored whether sleep quality was low during a
short-term (circuit break) quarantine restriction and
whether sleep quality was associated with participants’
overall attitudes about the pandemic using a validated
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512
scale.384 The project was performed online in England in
November 2020 and included 502 individuals aged >18.
Sleep quality was evaluated via the Pittsburgh Sleep
Quality Index (PSQI), and pandemic attitudes were as­
sessed via the Oxford Pandemic Attitudes Scale-
COVID-19 (OPAS-C), a validated 20-item, a 7-domain
scale that examines pandemic-related stress, fear,
loneliness, sense of community, sense of exaggerated
concern, non-pharmaceutical interventions, and vaccine
hesitancy. Unadjusted and multivariate logistic regres­
sion odds ratios of association were explored between
the dependent variable of poor sleep quality (PSQ I>5)
and risk factors, including OPAS-C score, age, sex,
educational level, and income. The mean PSQI score
was 7.62 ±3.49, with 68.9% of participants meeting the
criteria for poor sleep quality using the PSQI cutoff of >5.
The mean OPAS-C score was 60.3 ±9.1. There were
significantly elevated odds of poor sleep quality in the
highest v lowest OPAS-C quartiles (OR=4.94; 95% CI:
2.67-9.13; P<.0001). Age, sex, income, political orienta­
tion, employment status, and educational attainment
were not associated with poor sleep quality. It was con­
cluded that >2/3rds of respondents satisfied the criteria
for poor sleep quality. The odds of poor sleep quality
increased in a dose-response relationship with pandemic
attitudes (such as greater levels of pandemic-related
stress, fear, or loneliness). The association between poor
sleep quality and pandemic attitudes alludes to oppor­
tunities for public health and sleep medicine interven­
tions and showcases the importance of further research.
The COVID-19 pandemic has imposed extraordinary
and unpredictable alterations on daily life for an un­
known duration. As a result, core aspects of well-being,
including behavior, emotion, cognition, and social in­
teractions, have been negatively affected. Sleep and
circadian rhythms, with an extensive impact on phy­
siology, behavior, emotion, and cognition, have also
been affected. This review provides an updated overview
of the pandemic’s impact on circadian rhythms and
sleep based on the results of published studies (n=48) in
3 categories.385 The first section explored circadian
misalignment due to the pandemic in the general po­
pulation (including shift workers, health care staff, and
students) and patients with COVID-19. It summarized
the most important contributing factors to circadian
misalignment. Second, sleep difficulties and poor sleep
quality during the pandemic are examined, including
contributing factors, rate and prevalence, and impact on
the general population and patients with COVID-19.
Third, currently applied/recommended interventions for
aligning circadian rhythms and improving sleep quality
in the general population and patients with COVID-19
during the pandemic are summarized. The reviewers
note that circadian misalignment and sleep difficulties
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Volume 130 Issue 4
are expected consequences of the pandemic in the
general population (with the elderly, students, children,
health care, and night-shift workers as risk groups) and
patients with COVID-19. Home confinement and its
physiological, circadian, and psychological effects are
critical to these difficulties. Circadian and sleep problems
significantly impact symptom severity, treatment pro­
gress, recovery timeframe, and even diagnosis of
COVID-19. Therefore, behavioral interventions can be
beneficial for normalizing the factors contributing to
circadian and sleep difficulties.
Sleep and circadian phenotypes are associated with
certain diseases. This project examined whether sleep
and circadian phenotypes were causally linked with
COVID-19-related outcomes.386 Habitual sleep duration,
insomnia, excessive daytime sleepiness (EDS), daytime
napping, and chronotype were chosen as exposures.
Important outcomes included positivity and hospitaliza­
tion for COVID-19. This observational cohort study de­
rived multivariate risk ratios (RRs) and their 95% CIs.
Two-sample Mendelian randomization (MR) analyses
were conducted to estimate the causal effects of the sig­
nificant findings in the observation analyses. Odds ratios
(ORs) and the corresponding 95% CIs were compared
using inverse variance weighting, weighted median, and
MR-Egger methods. In the UK Biobank cohort study,
both often EDS and sometimes daytime napping were
associated with hospitalized COVID-19 (EDSoften vs. never
RR=1.24, 95% CI: 1.02-1.5; daytime nappingsometimes versus
never RR=1.12. 95% CI: 1.02-1.22). Moreover, sometimes
daytime napping was also associated with a higher risk of
COVID-19 susceptibility (RRsometimes versus. never=1.04;
95% CI: 1.01-1.28). In the MR analyses, EDS would raise
the risk of hospitalized COVID-19 (MR IVW method:
OR=4.53; 95% CI: 1.04-19.82), whereas little evidence
supporting a causal link between daytime napping and
COVID-19 outcomes. The investigators concluded that
observational and genetic evidence promotes a potential
causal link between EDS and a higher risk of COVID-19
hospitalization, suggesting interventions for EDS symp­
toms might reduce severe COVID-19 rates.
OSA has been proposed as a risk factor for severe
COVID-19 and is also associated with several known
risk factors for COVID-19. A population-based study
explored the association of sleep apnea with hospitali­
zation due to COVID-19 using a cohort with detailed
information on OSA and comorbidities.387 All commu­
nity-dwelling Icelandic citizens ≥ 18 years old and di­
agnosed with COVID-19 infection in 2020 were
included. Centralized national registries provided data
on demographics, comorbidities, and COVID-19 out­
comes. The centralized Sleep Department Registry at
Landspitali (the National University Hospital) supplied
diagnoses of OSA. Severe COVID-19 was defined as the
Cagna et al
October 2023
composite outcome of hospitalization and death. The
associations between OSA and the outcome were ex­
pressed as odds ratios (ORs) with 95% CIs, calculated
with logistic regression analysis and inverse probability
weighting. A total of 4756 people diagnosed with
COVID-19 infection in Iceland were included in the
study (1.3% of the Icelandic population), of whom 185
had a diagnosis of sleep apnea. In total, 238 were hos­
pitalized or passed away (38 had OSA). Adjusted for
age, sex, and BMI, OSA was associated with poor out­
comes (OR=2.2; 95% CI: 1.4-3.5); this association was
slightly attenuated (OR=2.0; 95% CI: 1.2-3.2) when
adjusted for demographic variables and comorbidities. It
was noted that OSA was associated with a twofold
elevated risk of severe COVID-19, and this was not
explained by obesity or other comorbidities.
A nationwide cross-sectional study described sleep-
related and mental health symptoms before and during
the COVID-19 pandemic and determined attitudes to­
ward help-seeking to treat these symptoms.388 An online
questionnaire was sent through the Brazilian Sleep As­
sociation’s social media to gather data, including socio­
economic and sleep aspects currently and before the
pandemic. Furthermore, questions addressed current and
previous anxiety, depression, and burnout symptoms.
Help-seeking was addressed in the survey and by a single
question asked when the participant reported mental or
sleep problems. The total sample included 6360 in­
dividuals, with a mean age of 43.5 ±14.3 years, 76.7%
female, and 63.7% with undergraduate or higher degrees.
Seventy percent of participants reported sleep dis­
turbances, and 80% described anxiety symptoms during
the pandemic. Only one-third demonstrated help-
seeking behavior. The hours of sleep decreased from 7.12
to 6.2, which coincides with the 28.2% increase in dis­
satisfaction with sleep duration during the pandemic. The
greatest frequency of sleep-related complaints was diffi­
culty falling asleep ≥3 times/week, from 27.6% pre-pan­
demic to 58.9% during the pandemic (P<.001). It was also
noted that help-seeking was more prevalent in men than
women and more in younger participants than in older
ones. The researchers concluded that self-reported sleep
and mental health problems increased during the pan­
demic and were not followed by more help-seeking.
The impact of sleep-disordered breathing (SDB) and
sleep-related hypoxemia in COVID-19 infection and
outcomes remains unclear, and controversy exists as to
whether continue treatment for OSA with CPAP given
concern for aerosolization with limited data to elucidate
professional organization recommendations. This case-
control study sought to examine the association of OSA
(diagnosed by PSG) and sleep-related hypoxemia with
severe acute respiratory syndrome-coronavirus-2 (SARS-
CoV-2) infection, and World Health Organization
(WHO) designated COVID-19 clinical outcomes while
Cagna et al
513
accounting for confounders including obesity, cardio­
pulmonary disease, cancer, and smoking history.389 The
study was conducted within the Cleveland Clinic Health
System (Ohio and Florida). It included all individuals
tested for COVID-19 between March 8 and November
30, 2020, with an existing sleep study report. Sleep indices
and SARS-CoV-2 positivity were explored with overlap
propensity score weighting, and COVID-19 clinical out­
comes were assessed using the institutional registry.
Outcomes were SARS-CoV-2 infection and WHO-de­
signated COVID-19 clinical outcomes (hospitalization,
use of supplemental oxygen, noninvasive ventilation,
mechanical ventilation or extracorporeal membrane oxy­
genation, and death).
Of 350 710 people tested for SARS-CoV-2, 5402 had
a prior PSG (mean age 56.4 ±14.5 yrs; 55.6% women;
n=3005), of whom 1935 (35.8%) tested positive for
SARS-CoV-2. Of the 5402 participants, 1696 were Black
(31.4%), 3259 were White (60.3%), and 822 were an­
other race or ethnicity (15.2%). Those who were positive
versus negative for COVID-19 had a greater AHI
(median AHI=16.2 events/hr, IQR: 6.1-39.5 events/hr,
P<.001 versus 1AHI=3.6 events/hr, IQR: 5.5-33.6 events/
hr; P<.001) and elevated percentage of total sleep time
(TST) at <90% oxygen saturation (median TST=18%,
IQR: 10-12.8%; P=.02 versus TST=1.4%, IQR: 10-10.8%,
P=.02). Following overlap propensity score-weighted
logistic regression, no SDB measures were associated
with SARS-CoV-2 positivity. Median TST <90 was as­
sociated with the WHO-designated COVID-19 ordinal
clinical outcome scale (adjusted OR=1.39; 95% CI: 1.10-
1.74; P=.005). Time-to-event analyses demonstrated
sleep-related hypoxia associated with a 31% greater rate
of hospitalization and mortality (adjusted HR=1.31; 95%
CI: 1.08-1.57; P=.005). This case-control study con­
cluded that SDB and sleep-related hypoxia were not
associated with increased SARS-CoV-2 positivity.
However, once patients were infected with COVID-19,
sleep-related hypoxia was an associated risk factor for
worse infection outcomes.
Another project produced a protocol paper de­
scribing the second survey produced by the
International Covid Sleep Study (ICOSS) group to
evaluate the associations between SARS-CoV-2 infec­
tion and sleep, sleepiness, and circadian problems as
possible predisposing factors for more severe COVID-19
disease and development of Long-COVID in the general
population.390 The survey comprised 47 questions on
sleep, daytime sleepiness, circadian rhythm, health,
mental well-being, life habits, and socioeconomic status
before and during the pandemic. For those previously
who tested COVID-19 positive, conditional questions
addressed vaccinations, specific sleep symptoms, or
sleep disorders. Surveys were to be administered online
between May and November 2021 in Austria, Brazil,
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Bulgaria, Canada, China, Croatia, Finland, France,
Germany, Israel, Italy, Japan, Norway, Portugal,
Sweden, and the USA. Data collected will contribute
important information on the open questions about
COVID-19 disease risk factors, symptomatology, and
evolution of Long-COVID, and other long-term con­
sequences related to the pandemic.
The COVID-19 pandemic has significantly affected
the mental and physical well-being of healthcare
workers (HCWs), impacting healthcare systems world­
wide. A year into the pandemic, the need to establish
the occurrence of sleep dysfunction and psychological
distress in the face of COVID-19, clarify risk and pro­
tective factors, and evaluate effective countermeasures
remained of critical importance.391 Despite implicit
limitations regarding the quality of available studies, a
great deal of evidence to date suggests that a substantial
proportion of HCWs undergo significant sleep dis­
turbances (estimated to afflict every two in five HCWs)
as well as mood symptoms (with >1 in 5 noting high
levels of depression or anxiety). Younger age, female sex,
frontline status, fear or risk of infection, occupation,
current or past mental health issues, and reduced social
support were all associated with a higher risk of dis­
turbed sleep and adverse psychological outcomes.
Moreover, the review explores the link between sleep
deprivation, susceptibility to viral infections, and psy­
chosocial well-being in relation to COVID-19; the ex­
isting evidence dealing with the presence and predictors
of traumatic stress/post-traumatic stress disorder (PTSD)
and burnout in HCWs is also summarized. Lastly, the
role of resilience and custom interventions to address
vulnerability and prevent long-term physical and mental
implications, promoting psychological resilience via an
enhanced social support network, has proven crucial for
HCWs in coping under strenuous circumstances. Future
research should focus on providing high-quality in­
formation on the long-term consequences and effec­
tiveness of applied interventions.
Patients with severe COVID-19 develop acute re­
spiratory distress syndrome (ARDS), necessitating ad­
mission to the intensive care unit (ICU). COVID-19 is
associated with an increased prevalence of comorbidities
like patients with sleep-disordered breathing. This pro­
spective cohort study examined the association between
undiagnosed SDB and the risk of ARDS and pulmonary
abnormalities in a group of COVID-19 survivors be­
tween 3 and 6 months following diagnosis.392 Patients
who developed ARDS during hospitalization because of
COVID-19 were prospectively compared with a control
group of participants who had COVID-19 with mild to
moderate symptoms. All individuals were evaluated
between the twelveth and twenty-fourth week after
SARS-CoV-2 infection. The evaluation includes persis­
tent symptoms, lung diffusing capacity of carbon
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monoxide (DLCO), chest CT scan, and HSAT. SDB was
diagnosed using the respiratory disturbance index (RDI)
≥ 5 events/hr. The association between SDB and ARDS,
the risks of lung impairment, and the hazard ratios were
evaluated. Sixty participants were included (ARDS=34;
controls=26). The mean follow-up was 16 weeks (range
12-24). ARDS reported a high prevalence of SDB (79%
versus 38% in the control group), with 35% of partici­
pants exhibiting DLCO impairment and 67.6% ab­
normal chest CT. SDB was independently associated
with ARDS (OR=6.72; 95% CI: 1.56-28.93; P<.01) and
abnormal chest CT (HR=17.2; 95% CI: 1.68-177.4;
P=.01). Furthermore, ARDS, days on mechanical venti­
lation and male sex were also associated with an ele­
vated risk of abnormal chest CT. It was concluded that
undiagnosed SDB is prevalent and independently as­
sociated with ARDS. In addition, undiagnosed SDB in­
creased the hazard of abnormal chest CT in the
midterm.
A systematic review and meta-analysis with regres­
sion investigated the extent of sleep disturbances during
the COVID-19 pandemic.393 Eleven databases and 6
preprint repositories were searched from November
2019, to July 2021. The DerSimonian and Laird method
was used to develop random-effect meta-analyses. Two
hundred fifty studies included 493 475 individuals from
49 countries. During the COVID-19 pandemic, the es­
timated global prevalence of sleep disturbances was
40.49% (CI: 37.56-43.48%). Bayesian meta-analysis re­
vealed an OR=.68 (CI:.59-.77), which translates to a rate
of approximately 41%. This demonstrates that the esti­
mated rate using classical meta-analysis is robust. Six
major populations were elucidated; the estimated pre­
valence of sleep problems was 52.39% (CI: 41.69-
62.88%) among patients infected with COVID-19,
45.96% (CI: 36.90-55.30%) among children and ado­
lescents, 42.47% (CI: 37.95-47.12%) among HCWs,
41.50% (CI: 32.98-50.56%) among special populations
with healthcare needs, 41.16% (CI: 28.76-54.79%)
among university students, and 36.73% (CI: 32.32-
41.38%) among the general population. Sleep dis­
turbances were more prevalent during lockdown than
no restrictions (42.49% vs 37.97%). Four in every 10
individuals noted a sleep problem during the COVID-19
pandemic. Patients infected with the virus, children, and
adolescents were the most impacted groups.
A different review article explored the management
of sleep issues during the COVID-19 pandemic.394 The
sleep of millions has been negatively impacted during
the pandemic; the impacted population includes the
public and HCWs. A prevalence of 20-45% is reported
globally for insomnia symptoms during this time. Sleep
deprivation in society leads to the increased strain of
COVID-related economic disruption, psychosocial is­
sues, substance abuse, and suicide. Disordered sleep is
Cagna et al
October 2023
not expected to disappear with the control of COVID-
19, stressing the necessity of interventions. The question
becomes how to manage sleep dysfunction during and
after the pandemic. Depression and anxiety are common
complaints during pandemic restrictions; insomnia
symptoms and fatigue persist even as mood improves in
those recovering from COVID-19 infection. Manage­
ment of disturbed sleep and mental health is especially
warranted in frontline HCWs. This overview involves 53
studies (as of February 2021) dealing with disturbed
sleep during the pandemic, treatment studies on
COVID-related sleep disturbance, and the need to rely
on current treatment guidelines for common sleep dis­
orders. The existing research from the first year of
COVID-19 has generally described symptoms of poor
sleep rather than dealing with treatment strategies. It
involves digital cognitive behavioral therapy for in­
somnia (CBT-T) for the general population and HCWs,
acknowledging the need for greater acceptance and ef­
ficacy of controlled studies of CBT for affected groups.
Suggestions based on a tiered public health model are
discussed.
Other works summarized the known associations
between COVID-19 and sleep dysfunction. They pro­
vided an overview of sleep medicine during the pan­
demic and looked into the future: insomnia, EDS, and
pandemic-related considerations for OSA and CPAP
therapies.395,396 Treatment strategies and management
options are also discussed. COVID-19 is a reminder that
global infectious disease outbreaks are not unique and
have the potential to cause devastating morbidity and
mortality, disrupt health care delivery, demand critical
decision-making in the absence of scientific evidence,
interrupt trainee education, wreak economic damage,
and contribute to a sharp rise in demand for health care
services that exceeds system capacity. Therefore, asses­
sing how the sleep medicine community dealt with
challenges brought on by the COVID-19 pandemic is
appropriate.
To mitigate viral transmission, the most effective and
efficient strategy was the rapid use of telemedicine.
Myriad additional strategies were implemented virtually
overnight, including more HSAT, reconsidering possible
risks of PAP therapy, a decrease or cessation of labora­
tory services, and deployment of workers to provide
frontline care to those infected with the virus. During
some periods, critical shortages in necessary personal
protective equipment, ventilators, and even oxygen
contributed to logistical challenges, intensified by per­
sistent financial constraints and insufficient staffing.
However, through ongoing innovation, resiliency, and
flexibility, breakthroughs were made in staff responsi­
bilities and workflow adaptations, using clinical areas,
seeking legislative support, and achieving professional
society collaboration. As a result, the missions of
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515
providing health care, teaching, and research pursuits
could continue. The summary reviews what has been
learned and specifics that need to be highlighted moving
into the future.
The COVID-19 pandemic, caused by SARS-CoV-2,
persisted throughout 2021. Highly effective vaccines be­
came widely available in 2021, and basic, translational,
and clinical knowledge about COVID-19 expanded at a
quick pace. This update reviews publications of the
American Thoracic Society and other journals that inform
a general understanding of pathophysiology, clinical
manifestations, vaccines, and treatment advances in
COVID-19 while considering broader impacts on society,
healthcare delivery, and medical education.397
The World Health Organization (WHO) is mandated
to compile and disseminate mortality statistics and has
followed the progression of the COVID-19 pandemic
since early 2020. Reported statistics on COVID-19
deaths are difficult for many countries due to variations
in testing access, differential diagnostic abilities, and
inconsistent certification of COVID-19 as the cause of
death. Beyond what is directly attributable, the pan­
demic has led to widespread collateral damage that has
led to loss of lives and livelihoods. This paper reports a
comprehensive and consistent measurement of the im­
pact of the COVID-19 pandemic by estimating excess
deaths by month for 2020 to 2021.398 The authors predict
the pandemic all-cause deaths in locations lacking
complete reported data using an over-dispersed Poisson
count framework that applies Bayesian inference tech­
niques to quantify uncertainty. They estimated 14.83
million excess deaths worldwide, 2.74 times more deaths
than the 5.42 million reported due to COVID-19 for this
timeframe. There are wide discrepancies in the excess
death estimates across the 6 WHO regions. Data and
methods employed to generate these estimates are de­
scribed and showcase the need for better reporting
where gaps persist. Various summary measures and the
hazards of ranking countries’ epidemic responses are
examined.
ORAL MEDICINE AND ORAL AND MAXILLOFACIAL
SURGERY
The literature review of the oral medicine (OM) and oral
and maxillofacial surgery (OMFS) section summarizes
the latest developments relevant to general dentists,
prosthodontists, and implant dentists. In the last years, a
particular focus was set on the implications of COVID-
19 for dentistry. The progression of the vaccination
campaign and increasing immunocompetence within
the population have reduced the challenges of the
pandemic for oral health providers, and the health
burden of COVID-19 is gradually fading. However, in
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this report's OM/OMFS section in 2021, oral mucosal
appearances of COVID-19 and the emergence of oral
lichen planus (OLP) as possible side effects of accredited
vaccinations were described.399 The scientific commu­
nity has made significant progress in researching the
etiology and treatment of OLP, a nagging problem that
impedes dental treatment, including the placement of
prosthodontic restorations. Therefore, all oral healthcare
providers must understand OLP. Here, all facets of OLP
will be concisely updated, including basic research, di­
agnosis, and available treatment options.
OLP is a disease affecting both the mucosa and the
attached gingiva. As the physiological and micro­
biological aspects of oral wound healing were elucidated
in the OM/OMFS review of 2021, this year’s report will
focus on anatomical intricacies of the gums (mainly
blood supply patterns and suggested incision designs)
with implications on wound healing and will highlight
their clinical relevance. Furthermore, the benefit of au­
tologous platelet concentrates on soft and hard tissue
healing processes will be explained in this section.
Oral Lichen Planus – New insights into an enigmatic
disease
OLP is triggered by an autoimmunologic activity of
mainly CD8 +T-lymphocytes against basal layer epi­
thelial cells of the oral mucosa.400 This reaction involves
the secretion of proinflammatory cytokines (tumor ne­
crosis factor-alpha, interferon-gamma, and interleukin
1, 2, 6, and the recently discovered 17) and causes ker­
atinocyte apoptosis.400-402 The sustained inflammatory
process creates epithelial damage and leads to the ty­
pical clinical appearances of OLP. The clinical image of
OLP is diverse. The most widely known form of OLP is
the reticular type (Wickham striae). The other types
(papular, plaque-like, erosive, bullous, and ulcerative)
are more challenging to diagnose. 402 However, there is
inconsistency in the nomenclature, and some authors
have suggested a simplification of the terminology with
a reduction into three OLP types (reticular, atrophic, and
ulcerative/erosive).400
The reason for T-cell activation is still unknown.401
The antigen that triggers the inflammatory response
might have an intrinsic or an extrinsic origin.401 The
majority of patients with OLP emerge without obvious
reasons (idiopathic). Due to a significant correlation with
OLP occurrence in patients suffering from hepatitis C,
researchers have suspected a viral trigger of OLP.401
Lucchese et al401 performed a meta-analysis of pub­
lished studies examining the potential role of herpes
viruses (HSV-1, -2, EBV, CMV) and papillomavirus
(HPV 16) and failed to find any correlations with ser­
opositivity for the mentioned viruses and OLP. Villa
et al400 summarized the available literature about
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possible effects of the oral microbiome and OLP de­
velopment and stated that overgrowth of specific bac­
terial strains might be associated with OLP. The
establishment of cause-and-effect relationships is still
impossible. Consequently, at present, OLP is likely as­
sociated with microbiological changes but possibly not
caused by them.400,401 To further elucidate the etio­
pathogenesis of OLP, Mallah et al403 assessed high-
quality studies dealing with the occurrence rates of OLP
and diabetes mellitus and found a moderate association.
Psychopathology has been presumed to be intertwined
with OLP occurrence.404 A topical systematic review
corroborated this theory.404 Further research will be
necessary in this field. The authors stated that the pre­
sent evidence needs to be more robust due to remark­
able bias in the analyzed studies.404
The overall prevalence of OLP in the general popu­
lation was estimated to be around 2%.405 estimate's
accuracy has been debated due to geographical differ­
ences and an unknown parent population.405.A recent
meta-analysis of demographical and epidemiological
studies concluded that the OLP prevalence is likely
lower (about 1%) and increases with age (especially >40
years).405 Geographical differences in OLP prevalence
rates could not be found.
OLP is considered to carry the risk of malignant
transformation (especially the active and ulcerative
forms). Studies have found transformation rates be­
tween 0.4% and slightly over 2% (higher in some stu­
dies). Newer publications have highlighted the
difficulties in interpreting these numbers due to incon­
sistencies in the nomenclature of OLP.406,407 While
some authors deem epithelial dysplasia in OLP lesions
as an exclusion criterion for diagnosing OLP, others do
not.406 Although the actual risk of malignant conversion
of OLP lesions is unknown, even lower than the re­
ported rates of roughly 2% warrants close clinical sur­
veillance of affected patients.407,408
OLP diagnosis should be made based on clinical
assessment and histopathological examination.409 Sur­
gical biopsies, especially when performed frequently, are
not well tolerated by affected patients. The application of
oral liquid brush cytology of OLP lesions with im­
munohistochemical evaluation protocols has been stu­
died by Idrees et al.409 The authors concluded that this
technique could be used with high accuracy and might
be a valuable adjunct to or even replace the surgical
biopsy to diagnose OLP in the future.
The mainstay of OLP therapy consists of topical
immunosuppressive drugs such as corticosteroids and,
in severe cases, calcineurin inhibitors (cyclosporin).402 In
the recent literature, many new agents have gained at­
tention due to their immunologic potential.402 Phos­
phodiesterase-4 inhibitors (Apremilast), biologicals
targeting relevant interleukins (interleukins l-17) or
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October 2023
tumor necrosis factor decoy receptors, systemic im­
munosuppressants, and newer drugs (Janus-kinase in­
hibitors) are currently used for patients with refractory or
excessive OLP where topical therapy has failed.402 While
systemic therapy regimens are usually not carried out by
oral health care providers, topical therapies (first line)
can be administered by dentists. As stated, locally ap­
plied corticosteroids are recommended as the primary
therapy of OLP.410 A recent systematic review confirmed
the superiority of clobetasol(-propionate) containing
solutions (0.025%-0.05% dilution) over other corticos­
teroids (dexamethasone).410 The injection of platelet-
rich fibrin into OLP lesions has been proposed as a vi­
able alternative to corticosteroids.411-413 The initial re­
sults have shown good efficacy of iPRF use without
remarkable side effects. The following paragraph will
discuss the new developments of second-generation
platelet concentrates. Furthermore, Vitamin D and cur­
cumin supplementation have been reported to alleviate
the burden of OLP.414,415
The implications of OLP on dental treatment are
complex. While OLP has been identified as a risk factor
for the exacerbation of periodontitis,416 its presence does
not seem to decrease implant survival.417,418 Removable
prostheses are associated with an increased rate of OLP
and other potentially premalignant oral mucosal le­
sions.419 The placement of fixed prosthodontic restora­
tions may be favorable in OLP patients whenever
possible.
Innovations in autologous platelet concentrates
Autologous platelet concentrates (APC) have been used
clinically for over 20 years.420 Numerous different APCs
are currently promoted and advertised. These differ sig­
nificantly in the manufacturing process, applicability, and
clinical benefit.420 The primary and most widely known
APC is platelet-rich plasma (PRP). Despite an abundance
of studies about the efficacy and applicability of PRP that
have been carried out since the beginning of the mil­
lennium, the superiority of PRP administration has not
been proven beyond doubt, which is due to the large
array of PRP formulations and limited homogeneity of
the study results.421 In 2001, Dohan et al422 further de­
veloped the idea of APCs and described the second-
generation APC, called platelet-rich fibrin. The main
differences between PRP and PRF are depicted in Table 1.
Table 1. Biologic characteristics of PRP and PRF (autologous platelet
concentrates)
PRP PRF
Blood collection with anticoagulant Blood collection without
anticoagulant
Two centrifugation steps One centrifugation step
Liquid concoction, sometimes Gel-like concoction
activated with coagulant before
clinical use
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Different types of PRP and PRF can be created by
changing the centrifugation speed and time. In addi­
tion,420 PRP and PRF can be prepared as injectable
formulations (iPRF, where i=injectable).
High-quality studies examining the benefits of PRF
on oral wound healing procedures (soft tissue and hard
tissue) are rare, which makes the design of meta-ana­
lyses difficult. PRF formulations in oral surgical soft
tissue procedures will likely expedite wound healing
processes and reduce swelling and postoperative pain
within the first days after surgery.423 This effect seems to
fade after about one week.423
In recent years, the use of PRF has been researched in
virtually every field of dentistry. Favorable effects of PRF
in regeneration procedures for periodontal intrabony
defects,424,425 gingival recession surgery (especially Miller
class I and II, with a low level of evidence),238 apexifica­
tion of immature teeth after endodontic treatment426 and
the treatment of internal derangements, osteoarthritis
and arthrosis of the TMJs have been reported.427 It is still
unclear whether PRF improves bone healing and is sui­
table for ridge preservation procedures after tooth ex­
tractions (ambivalent evidence).428,429 The superiority of
adding PRF to xenografts in sinus lifting procedures has
yet to be proven.430
In summary, PRF augments the predictability of a
wide array of oral surgical interventions and improves
postoperative patient comfort. Therefore, its wide clin­
ical use can be advocated.
Recent development of oral mucosal anatomy and
perfusion schemes
Understanding the anatomy of oral mucosal structures is
important for all oral health care providers. Recently,
some new insights into gingival perfusion patterns have
been provided. Mikecs et al431 examined the artery and
arteriole anatomy in the oral mucosa of the esthetic zone.
They found that the gingiva in the anterior maxilla re­
ceives at least three vertically oriented affluent vessels
from the superior labial artery, which decrease in dia­
meter toward the alveolar crest and spread out horizon­
tally in their terminal branches beyond the mucogingival
junction. Compression or severing of those arteries sig­
nificantly impacts the adjacent areas and creates hor­
izontal ischemic patterns. Even if only minimal areas of
the vestibular mucosa are compressed, the effect on the
marginal gingiva may be excessive. The authors highlight
the importance of avoiding vertical vestibular incisions
and excessive flap tension in any surgical procedure in­
volving marginal gingival structures.
Shahbazi et al432 also investigated the perfusion
patterns of the maxillary vestibular mucosa. They con­
firmed the importance of the superior labial artery (SLA)
for the blood supply of the mucosa in the esthetic zone.
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518
Still, they stated that the periosteum in this area received
its nutrition from terminal branches of the infraorbital
artery (IOA). Posterior superior alveolar artery (PSAA)
components nourish the oral soft tissues in the molar
and premolar areas. Cadaveric studies performed by the
authors revealed that interseptal anastomoses connect
vestibular and palatal blood vessels.432 A high density of
blood vessels was noted in the upper lip frenulum,
which makes this area a “safe zone” for releasing inci­
sions. Due to the segmental organization of the vestib­
ular blood supply between the PSAA, the IOA, and the
SLA, another safer zone for a vertical incision is the area
distal to the canine. This marks the natural division
between the PSAA and IOA perfusion areas, and thus
nutrition deficiencies will occur with less likelihood.
These findings contrast with the results of Kleinheinz
et al433 published in 2005, who stated that the maxillary
vestibular blood supply was mainly based on branches
of the IOA. None of the authors found differences in the
known vascular architecture of the mandible, which is
dependent on facial artery branches (vestibular) and
sublingual/submental artery branches (lingual aspect).
Gingival blood flow seems to be reduced in bruxism
patients during clenching.434 The use of a new tooth­
brush has been shown to increase gingival micro­
circulation and might therefore be protective of gingival
inflammation.435
CARIES AND CARIOLOGY
The scientific literature related to dental caries and car­
iology was extensive in 2022. Selected articles are re­
viewed in 8 general fields: Global Considerations,
Behavioral Considerations, Diagnostic Protocols,
Preventive Protocols, Use of Silver Diamine Fluoride,
Root Caries, Deep Caries Removal Strategies, and the
Relation Between Vaping and Caries Risk.
Global considerations
One interesting study attempted to characterize the
burdens, trends, and inequalities of untreated caries at
the global, regional, and national levels between 1990
and 2019 through various analytical approaches.436 The
prevalence of dental caries in permanent and deciduous
teeth decreased by 3.6% during this time, and caries
prevalence in permanent dentition was lower in more
developed countries. Globally, over 60 million cases of
caries were attributable to sociodemographic inequality
in 2019. The burden of dental caries remains a global
public health challenge.
A review article attempted to make the case that
dental caries is a non-communicable disease,438 flying in
the face of Anderson’s classic paper in 1993 discussing
managing dental caries using the medical model and
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Volume 130 Issue 4
identifying specific biofilm bacteria responsible for de­
mineralizing tooth structure.439 The authors declare that
caries prevention and management is about controlling
risk factors to maintain a balanced intraoral biofilm
ecology that guards against a continuing low pH driven
by the frequent consumption of sugars. They believe
caries control is no longer about attempts to eradicate
specific microorganisms It should be classified as a non-
communicable disease with similar risk factors to other
chronic/systemic diseases. This approach provides op­
portunities for developing common preventive strategies
that promote health equity through action on the social
determinants of health. Readers are cautioned to accept
these conclusions with a healthy degree of skepticism.
Another self-congratulatory article from the same
group describes why well-intentioned global collaborations
educating the profession and public about dental caries
prevention are essential.440 The article also successfully ex­
plains why these global collaborations are meaningful and
are inherently difficult to create and manage.
A group of collaborators from the United Kingdom
and Brazil published an article exploring the relationship
between obesity and childhood caries in the United
States.441 Three standards were used to define obesity,
and 3 different parameters were used to measure caries
prevalence. The results were predictably unintelligible,
and obesity was related to the prevalence of caries when
using some parameters but not with others. However,
the primary conclusion was that the relationship be­
tween obesity and dental caries varied based on the
definition of obesity and dental caries used.
Another paper asked, “Does dental caries lead to
stunting and wasting in children?”442 This was a review
of a systematic review published earlier in 2022.443 In­
cluded in the initial study were 38 articles about wasting
and stunting. For the permanent dentition, the balance
of evidence showed no relation between caries pre­
valence or severity with wasting. However, positive as­
sociations between dental caries prevalence and severity
with wasting and stunting were found for the primary
dentition. However, the authors cautioned that the
complexity of synthesizing dental and nutritional data,
dentition type, age, and income status, made drawing
definitive conclusions extremely difficult.
An umbrella review evaluated the results of 18 sys­
tematic reviews on the effectiveness of minimal inter­
vention dentistry for managing carious lesions into dentin
in primary teeth.444 The interventions evaluated were 38%
sodium diamine fluoride, the Hall technique, selective
caries removal, and atraumatic restorative treatment. It
was concluded that minimal intervention dentistry tech­
niques were effective in arresting the progress of dentinal
caries in primary teeth compared to no treatment. The
authors claimed that these techniques should be con­
sidered a mainstream option rather than a compromise to
Cagna et al
October 2023
conventional approaches when such approaches are im­
possible due to lack of cooperation or cost.
Behavioral considerations
A cross-sectional study from Turkey asked the question,
“Can sleeping habits be associated with sleep bruxism,
TMDs, and dental caries among children”?445 One
hundred children aged 6 to 13 years were included in the
study, which consisted of a parental questionnaire, in­
traoral and TMD exam and a sleep study. Bedtime re­
sistance was significantly associated with sleep bruxism
and TMD symptoms. Untreated dental caries was sig­
nificantly associated with sleep fragmentation. Readers
are cautioned that association is not synonymous with
causality.
Another cross-sectional study investigated associa­
tions among internet addiction, lifestyle behaviors, and
dental caries in 1562 high school students in Southwest
Japan.446 Internet addiction (IA) was characterized by a
Young’s Internet Addiction test score of greater than 50.
The unhealthy lifestyle behavior index (ULBI) was de­
termined by a cumulative count of 8 different lifestyle
behaviors. Dental caries was determined by the number
of decayed, missing, and filled permanent teeth (DMFT).
Internet addiction was observed in 406 participants and
was associated with a larger DMFT. A higher ULBI was
associated with both IA and a larger DMFT.
Diagnostic protocols.
A cross-sectional study established the correlation
between an index for caries treatment needs and an
index for caries lesion detection and evaluation.447 There
were 3 samples of children based on age (age 3 years,
n=302; age 5 years, n=183; and age 11 to 14 years, n=60.
Dental caries treatment needs were estimated for every
child through the Caries Treatment Needs Index (CTNI).
A diagnosis of dental caries was made according to
ICDAS II criteria operationalized by grouping the codes
into 4 categories. There was a significant correlation
between both indices in all groups of the 3- and 5-year-
old participants and between 3 of the 4 groups in 11- to
14-year-old participants. The authors felt the statistical
evidence was sufficient to demonstrate reasonable
equivalence for both indices (CTNI) and (ICDAS II) for
use in future clinical and epidemiological studies.
A review study compared the diagnostic ability of
near-infrared imaging (NIRI) with other diagnostic tools
for dental caries.448 Conventional diagnostic methods,
including visual/tactile inspection and conventional
radiography, have low sensitivity and are ineffective
with early caries diagnosis. Late caries detection is as­
sociated with increased loss of tooth structure. NIRI has
excellent potential as an early diagnostic tool. NIRI uses
light ranging from 700 to 1700 nm, which has better
optical properties than conventional optical systems
Cagna et al
519
using light in the visible spectrum. It enables deeper
light penetration into tooth tissue, weak scattering,
lower background noise, and strong photon absorption
with detailed images. NIRI does not require ionizing
radiation. Several in vivo studies have demonstrated that
NIRI technology has the potential to improve perfor­
mance compared with current diagnostic methods. It
exhibits increased sensitivity compared to radiographs
and is more suitable for identifying approximal enamel
lesions. Limitations of NIRI include difficulty in asses­
sing lesions adjacent to existing restorations and asses­
sing the proximity to the pulp, as it cannot gauge to
outline of the pulp. No discussion of time and costs were
included in the study.
A descriptive article discussed dental caries diagnosis
using terahertz spectroscopy (THz) and birefringence.449
THz waves with highly penetrating and non-ionizing
properties are ideally suited for early dental caries di­
agnosis; however, the research is in its infancy. This
article discusses available evidence regarding this tech­
nology and studies that need to be done to increase the
accuracy of THz technology in detecting dental caries
and stimulate the development of THz caries instru­
ments. While not yet ready for prime-time use, THz
technology has excellent potential as a new tool for
caries diagnosis.
A cross-sectional study of 400 Brazilian school chil­
dren in a disadvantaged region was carried out to in­
vestigate the role of dental pain and psychosocial factors
on the relationship between dental caries and
OHRQoL.450 Several predictors, including OHRQoL,
DMFT, dental pain, and social support, were collected
and subjected to statistical analysis. The number of
dental caries was indirectly linked with OHRQoL
through dental pain and social support. The authors
concluded that tackling dental caries and psychosocial
factors may attenuate the impact of oral health on
OHRQoL in children.
Preventive protocols
A systematic review (including 32 studies and 1 systematic
review) evaluated the efficacy of screening and fluoride
application in children younger than 5 years.451 The results
were disappointing but are probably the best evidence
available. The data showed neither benefit nor harm with
primary oral health screening or referral to a dentist.
However, dietary fluoride supplementation and the use of
fluoride varnish were associated with improved caries
outcomes in higher-risk children and settings.
A narrative review article evaluated studies on hy­
droxyapatite toothpaste (HAP) to prevent dental
caries.452 Caries is a process of demineralizing enamel
and dentin due to the dissolution of hydroxyapatite at
low pH. HAPs have been shown to restore
THE JOURNAL OF PROSTHETIC DENTISTRY
520
demineralized enamel surfaces and are attractive to
some because they are a fluoride-free anti-caries agent.
The article summarizes in vitro, in situ, and in vivo re­
search findings related to the remineralization potential
of HAP. The authors are very enthusiastic about this
product and declare that HAP is a biomimetic oral care
agent with a high safety profile and no risk of fluorosis.
However, the reality is that there is no evidence that
HAP is superior to fluoride-containing toothpaste in
preventing or arresting dental caries. However, it may be
a decent alternative for young children where fluorosis is
a concern.
Another narrative review addresses restorative ma­
terials containing quaternary ammonium compounds
coupled with organic silica into minute particles (QASi)
that potentially have sustained antibacterial action.453
Because secondary caries adjacent to existing restora­
tions account for 40% of needed restorations, restorative
materials with antibacterial properties might prevent or
reduce this problem. Several composite resin materials
with incorporated antibiotic agents have been tested in
recent years, but their effectiveness has been limited
because the agents are exhausted over time. Based on
laboratory and limited human studies, the QASi mate­
rials retain their antibacterial action over time without
leaching or losing activity. They also have mechanical
properties comparable to contemporary materials and
have been cleared for use by the FDA. While further
investigation is needed, these materials can reduce
secondary caries adjacent to existing restorations which
is a significant problem with composite resin materials.
A systematic review evaluated the efficacy of nano-
hydroxyapatite (nHA) on caries prevention.454 Ten in
vivo and in situ studies were included in the analysis.
Under demineralizing situations, NaF was able to hinder
demineralization, whereas nHA did not, and the results
were the same as with a fluoride-free control. Under
remineralizing conditions, NaF and nHA had the same
remineralizing potential. However, the level of evidence
was very low. Therefore, the authors concluded that
there is no conclusive evidence on the efficacy of nHA.
Several additional articles investigated novel ap­
proaches to prevent dental caries. In the interest of
brevity, these studies will be referenced and described in
a sentence or two. One study evaluated the efficacy of
dual-sensitive antibacterial nanoparticles to prevent
dental caries.455 The results demonstrated the high ef­
ficacy of dual-sensitive antimicrobial peptides for the
selective damage of bacterial biofilms, which may pro­
vide an efficient strategy for preventing dental caries.
Another systematic review evaluated caries manage­
ment with non-metallic nanomaterials.456 Non-metallic
nanomaterials do not stain enamel or dentin and have
good biocompatibility. However, this review
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
demonstrated that non-metallic nanomaterials have
antibacterial properties based primarily on in vitro stu­
dies, so their clinical efficacy is still being determined.
Another review article proposed that nano­
technology-based therapies for preventing and treating
Streptococcus mutants-derived dental caries may be ef­
fective because they improve the retention of the ther­
apeutic agents in the biofilm in the oral cavity.457
Streptococcus mutans is the principal cariogenic biofilm
constituent because it produces an extracellular poly­
meric substance (EPS) which allows the biofilm to bind
to the tooth structure and eventually mature and cause
acidic demineralization. A review article evaluated re­
search on several different strategies through EPS dis­
ruption.458 Another approach to minimize the effect of
Streptococcus mutans in dental caries is to use microbiota-
derived postbiotic mediators (PMs). One interesting
study evaluated findings that indicate that microbiota-
derived PMs may have a preventive role in the patho­
genesis of dental caries.459 A review article evaluated the
effectiveness of bacterial extracellular signaling systems,
known as quorum sensing, to disrupt oral biofilm for­
mation and thus prevent oral infectious diseases such as
dental caries.460 Natural compounds such as trans-cin­
namaldehyde have been shown to disrupt biofilm as­
sembly, but finding a way to deliver such hydrophobic
biologic molecules has been difficult. One group of in­
vestigators found that using porous silicon micro­
particles could effectively provide a controlled cargo
release over 14 days and significantly reduce biofilm
formation by downregulating glucan synthesis and
hindering acid production.461
Use of sodium diamine fluoride
Sodium diamine fluoride (SDF) has gained attention
recently as an agent to arrest caries in primary teeth and
prevent and arrest root caries in elderly patients. When it
was first introduced, acceptance in North America was
limited because the arrested caries lesions were stained
black. Consequently, most of the early research on this
material was done in China and South America.
However, because SDF is so effective in arresting caries
in young and elderly patients, its use has gained po­
pularity in North America, and numerous articles related
to SDF were published in 2022. Readers are referred to
the section on Dental Materials and Therapeutic Agents,
which reviewed 9 articles about SDF. The following
narrative will examine several more.
Yet another study was published on the efficacy of
SDF and potassium iodide in arresting caries with re­
duced discoloration.462 Several previous studies have
shown that potassium iodide does not inhibit the ef­
fectiveness of SDF but provides only a marginal
Cagna et al
October 2023
reduction in discoloration. This in vitro study using ar­
tificial caries and bovine teeth affirmed the results of
previous studies.
Another study evaluated the parental perception of
SDF treatment outcomes for managing dental caries in
children.463 The study used a cross-sectional survey of
parents of children 2-10 years of age. Most parents were
receptive to SDF treatment. However, the treating den­
tist’s advice, cost, and aversion to more invasive treat­
ment were significant factors in their decision-making.
An important review article investigated published
protocols for the use of SDF.464 An earlier study in­
vestigating teaching related to SDF in US dental schools
found that 66% of schools were using SDF, but only 18
of 66 schools had clear protocols for use.465 The review
included 14 protocols from 15 different publications.
Protocols were recommended by manufacturers (n=4),
dental associations (n=3), and author teams (n=7), and
application times ranged from 10 to 240 s, with the
majority suggesting 60 s. Some publications re­
commended limited caries removal before application,
while others suggested no excavation. There were many
other protocol variations involving isolation techniques,
drying the lesions, methods of application, removing
excess SDF solution, and whether to apply fluoride
varnish to the SDF-treated lesion. While SDF is an ef­
fective agent for arresting and preventing caries, there is
an obvious need for continued research into optimum
protocols for use in specific situations.
Another important article attempted to identify the
top 100 cited articles related to SDF.466 It was described
as a bibliometric analysis and accessed 4 significant
databases. The category with the most articles was
clinical trials (n=24), followed by systematic reviews
(n=12), literature reviews (n=14), and narrative reviews
(n=12). The highest number of most-cited papers ori­
ginated in China and the USA. The most studied out­
come was caries arrest. This paper is a valuable resource
for any investigator interested in this field.
A marginal in vitro study compared the relative
ability of silver nitrate and SDF to affect dentin re­
mineralization and the relative cytotoxicity to dental
pulp cells of the 2 materials.467 The rationale for the
study was that silver nitrate is already available in many
countries and is less expensive. The results showed that
SDF was superior in remineralization potential, and the
cytotoxic effects were similar.
An in vitro study using bovine teeth and artificially
induced early enamel caries lesions compared the effi­
cacy of SDF and fluoride varnish to remineralize the
lesions.468 The study was done in 2 stages. In the first
stage, SDF was superior to other agents in reminer­
alizing the lesions. In the second stage, fluoride varnish
was superior to SDF in preventing demineralization. The
authors concluded that fluoride varnish is a better choice
Cagna et al
521
over SDF for treating early, incipient, non-cavitated,
white-spot enamel lesions. However, readers are ad­
vised to accept this conclusion with caution due to the
relatively low level of evidence.
A study evaluated the use of SDF in a children’s
hospital.469 Conclusions were based on 13 articles. SDF
has been used effectively with children 1 year of age and
up. Their recommended protocol was 38% SDF applied
twice yearly. The primary reported complication was
staining. The authors developed a decision algorithm for
patients attending their hospital. They concluded that
SDF treatment was extremely useful in children between
0 and 4 years of age and in patients with special health
care needs aged 0 to 18.
An in vitro study measured free fluoride, silver ion
concentrations, and pH of 4 commercially available 38%
SDF solutions.470 The mean fluoride concentrations in the
solutions ranged from 43 233 to 54 400 ppm. The mean
concentrations of silver ions ranged from 258 841 to 319
966 ppm. The pH values ranged from 9.0 to 9.2. The
measured values of fluoride, silver ions, and pH were
slightly different between the 4 products, but there is no
indication that differences in their clinical efficacy exist.
A systematic review on the efficacy of nonrestorative
caries treatment updated previous reviews on the same
subject.471 All 35 included articles presented results of
RCTs with a follow-up period of 6 to 84 months. The
modalities studied were sealants, fluoride gels and
varnishes, resin infiltration, and SDF. The authors con­
cluded that new articles published between 2017 and
2022 provide further evidence of the effectiveness of
non-restorative caries treatment options.
Two articles presented different outcomes related to
the bond strength to dentin of glass ionomer cement
pretreated with SDF. The first article was an in vitro
study that compared microtensile bond strength (µTBS)
to sound dentin and artificial caries-affected dentin.472
Dentin exposed to an artificial caries process and sound
dentin were treated with 38% SDF and immediately
restored with Fuji IX. Results showed that µTBS was
reduced to sound dentin, while no differences were
found in the µTBS to artificially caries-affected dentin.
The second study was a systematic review and meta-
analysis of the bonding performance of adhesive mate­
rials to SDF-treated dentin.473 Twenty-two studies were
used in the systematic review and 21 in the meta-ana­
lysis. SDF dentin pretreatment did not influence the
glass ionomer bonding independent of the dentin con­
dition. SDF pretreatment impaired the bonding with
adhesives; however, a rinsing step after SDF eliminated
this effect in sound dentin and increased the bond
strength to caries-affected dentin.
To summarize this section, SDF has become an es­
sential modality for preventing and arresting caries in
pediatric and elderly patients. The optimum protocol in
THE JOURNAL OF PROSTHETIC DENTISTRY
522
either situation has yet to be scientifically validated, but
SDF is efficacious in both groups of patients. More re­
search is needed to define the best protocols regarding
the time of application, partial caries removal in deep
lesions, the number of applications per year, and the
necessity for spackling.
Root caries
A narrative review evaluated previous research on using
SDF for root caries management.474 The important
contribution to the literature of this paper was the
proposal of a specific protocol for managing root caries.
The authors propose removing the superficial carious
dentin with deep lesions, followed by 2 applications of
SDF about 1 week apart. After that, the dentin will be
dark and hard, and the lesion can be restored with GI,
RMGI, or composite resin.
A systematic review evaluated the clinical evidence
for professionally applied fluoride to prevent and arrest
dental caries in elderly patients.273 Out of 527 identified
studies, 7 were included in the review. Positive results
were found for the use of 5% NsF varnish, 1.3% APF,
and SDF. The significant findings were that 5% NaF
varnish and 1.23% APF gel prevented root caries, and
38% SDF solution prevented and arrested root caries.
An analytic article reviewed the previous systematic re­
view and supported the search and analysis of the in­
cluded studies, validating the conclusions.475
A study from the UK developed a root caries pre­
diction model based on data collected from a population
of elderly dental attendees.476 Data collected from 1432
participants was assessed at baseline and 4 years. Pre­
diction parameters of root caries prevalence included:
increasing age, having 9 or more teeth restored at
baseline, smoking, decreasing dental anxiety, and wor­
sening OHRQoL. The data indicate that adults at risk for
developing root caries can be accurately identified, and
appropriate preventive procedures be recommended
and implemented.
Deep caries removal
Protocols for removing “deep caries” have evolved
over many years. The traditional approach was
“complete” caries removal, which is very subjective,
almost impossible to calibrate and frequently resulted
in pulp exposure with concomitant complications.
Current protocols call for “selective” caries removal,
where the deep caries are circumscribed, left in place,
and a “well-sealed” restoration is placed. Research
has shown this approach has lower odds of treatment
failure than the conventional technique for complete
caries removal.477 A national dental practice-based
network study used a cross-sectional questionnaire to
assess practitioners’ use of selective caries removal
THE JOURNAL OF PROSTHETIC DENTISTRY
Volume 130 Issue 4
when treating deep caries in asymptomatic and
symptomatic teeth.478 Five hundred dentists re­
sponded to the questionnaire, with 60% working in
private practice settings. Selective caries removal was
appropriately used more frequently with asympto­
matic lesions than with symptomatic lesions. The
study's primary finding was that selective caries re­
moval is used more often than in the past based on
previous studies but is still underused by many prac­
titioners. In addition, the usual recommendation of
increased dissemination of knowledge and continuing
dental education activity were made.
A UK-based questionnaire study found that sig­
nificant variation occurs in managing deep caries.479
Results showed that NHS practitioners were less likely
to use rubber dams and use selected caries removal than
practitioners with post-graduate qualifications. The au­
thors concluded that although clear guidelines are
available, this needs to translate into consistent man­
agement approaches in practice.
An expert consensus article on caries management
noted that although knowledge of the prevention of
caries is well understood, the incidence and prevalence
of dental caries are still relatively high.480 The sub­
sequent discussion of performing caries risk assessment
and developing a caries treatment plan offers nothing
new to managing dental caries.
Relationship between vaping and dental caries
Two critical studies evaluated the relationship between
e-cigarette or vaping use and dental caries. First, an in
vitro study demonstrated that exposure to e-cigarette
aerosol suppressed the growth of commensal strepto­
cocci and favored the development of streptococcus mu­
tans.481 The study also showed that e-cigarette aerosols
significantly increased biofilm formed by streptococcus
mutans but did not affect biofilm formation by com­
mensals. The data from this study indicates that routine
use of e-cigarettes can increase the caries susceptibility
of users.
A cross-sectional study compared the caries risk of
patients with a history of vaping versus those without.482
The records of 13 098 Tufts School of Dental Medicine
patients were searched to assess the relationship be­
tween the use of e-cigarettes and caries risk. Patients
who vaped were at significantly higher levels of caries
risk than those who did not use e-cigarettes. The study
indicates the need to include vaping history in routine
medical and dental history.
In summary, dental caries research was conducted at
a high level in 2022. While no silver bullets were dis­
covered, our understanding of the disease process and
how to prevent that process have continued to progress
and build on the research of pioneers in the field.
Cagna et al
October 2023
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Corresponding author:
Dr David R. Cagna
Department of Prosthodontics
University of Tennessee Health Sciences
Center College of Dentistry
875 Union Avenue
Memphis, TN 38163
Email: dcagna@uthsc.edu.
CRediT authorship contribution statement
Annual review of selected scientific literature: A report of the Committee on
Scientific Investigation of the American Academy of Restorative Dentistry.
David R. Cagna, DMD, MS: Conceptualization, Investigation, Writing, and
Project Administration. Terence E. Donovan, DDS. James R. McKee, DDS.
Frederick Eichmiller, DDS. James E. Metz, DDS. Riccardo Marzola, DDS.
Kevin G. Murphy, DDS, MS. Matthias Troeltzsch, MD, DMD, PhD:
Conceptualization, Investigation, and Writing.
Copyright © 2023 by the Editorial Council of The Journal of Prosthetic Dentistry.
All rights reserved.
https://doi.org/10.1016/j.prosdent.2023.06.001
Cagna et al