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Aging and Oral Health: Effects in Hard and Soft


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Current Pharmaceutical Design, 2010, 16, 619-630

619

Aging and Oral Health: Effects in Hard and Soft Tissues


R. Guiglia1, A. Musciotto1, D. Compilato1, M. Procaccini2, L. Lo Russo3, D. Ciavarella3, L. Lo Muzio3, V.
Cannone4, I. Pepe4, M. DAngelo1 and G. Campisi1,*
1

Department of Oral Sciences, University of Palermo, Italy; 2Oral Sciences Institute of Polytechnic University of Marche, Ancona,
Italy; 3Department of Surgical Sciences, University of Foggia, Italy; 4Department of Clinical Medicine and Emerging Diseases,
University of Palermo, Italy.
Abstract: Changing demographics, including an increase in life expectancy and the growing numbers of elderly has recently focused
attention on the need for geriatric dental care. Ageing affects oral tissues in addition to other parts of the human body, and oral health
(including oral mucosa, lips, teeth and associated structures, and their functional activity) is an integral component of general health;
indeed, oral disease can cause pain, difficulty in speaking, mastication, swallowing, maintaining a balanced diet, not to mention
aesthetical considerations and facial alterations leading to anxiety and depression. The World Health Organization recommends the
adoption of certain strategies for improving the oral health of the elderly, including the management and maintenance of oral conditions
which are necessary for re-establishing effective masticatory function. Oral health is often neglected in the elderly, and oral diseases
associated with aging are complex, adversely affecting the quality of life. Although oral health problems are not usually associated with
death, oral cancers result in nearly 8,000 deaths each year, and more than half of these occur at an age of 65 years plus. This report, which
is dedicated to geriatric physicians, geriatric dentistry and specialists in oral medicine reviews age-related oral changes in elderly patients
and efforts to summarize the effects of aging in hard and soft oral tissues.

Keywords: Ageing, oral health, quality of life, geriatrics, dental care, oral medicine, elderly, oral mucosal conditions, periodontal diseases;
salivary glands; burning mouth syndrome.
INTRODUCTION
Ageing is an inexorable process which causes homeostasis
disequilibrium, increased vulnerability, in addition to reduced
adaptation to environmental stimuli, affecting cells, tissues, organs
and bodily systems. All these phenomena are associated with an
increased predisposition to illness and death. The debate continues
as to whether the physiologic and pathologic changes characterizing
ageing are due to the ageing process itself or to diseases,
medications, or environmental changes to which ageing people are
exposed. For certain, the global proportion of older people is
growing faster than of any other age group with approximately 600
million people aged 60 years and over, and this number will double
by 2025. This implies that, with more people living longer, there
will also be an increase in the prevalence of systemic and oral
diseases which need to be addressed for effective prevention,
therapy and rehabilitation.
Ageing per se exerts various effects on oral tissues and
functions. The elderly are at risk of chronic diseases of the mouth,
including dental infections (e.g., caries, periodontitis), tooth loss,
benign mucosal lesions, and oral cancer. Other common oral
conditions to be found in this population are xerostomia (sensation
of dry mouth) and oral candidiasis, which may may manifest itself
as acute pseudo-membranous candidiasis (thrush), erythematous
lesions (denture stomatitis), or angular cheilitis.
Generally, the most common oral condition in the elderly is
tooth loss due to dental caries or periodontal disease (PD). Indeed,
the number of teeth in the arches is considered as a measure of oral
health status, since retaining less than 20 teeth causes masticatory
difficulties and reduced swallowing. Many systemic conditions
(e.g., xerostomia, orofacial pain and oral and pharyngeal cancer,
typical in the elderly) and socio-economic factors (e.g., costs,
educational background, social class) interfere with the maintenance of a functioning dentition and a healthy oral cavity may
have local and systemic effects/implications [1].

*Address correspondence to this author at the Department of Oral Sciences,


University of Palermo, Corso Tukory 211, 90134 Palermo, Italy;
Tel/Fax: +39 91 6552236; E-mail campisi@odonto.unipa.it
1381-6128/10 $55.00+.00

Establishing the links between oral diseases and general health


is not easy but poor oral health found in older adults can lead to oral
infections, tooth loss, caries, PD, abscesses, xerostomia, oral
precancerous lesions or cancer [2]. Ageing is often associated with
systemic disorders and their treatment (e.g., medication, radiation
therapy, chemotherapy) can influence oral health and oral functions
[3-5]. Potential mechanisms of correlation between oral health
problems and systemic conditions have been reported in the
literature [6]. In particular, Kuo et al. [7] have examined the
association between PD(s) and common systemic diseases, like
diabetes, chest infections and respiratory diseases, cardiovascular
diseases and osteoporosis (OP) in a recent review. PD has been also
associated with preterm low birth weight [8], rheumatoid arthritis
[9], pancreatic cancer [10], and recently with Alzheimers disease
[11,12].
Oral health is currently held to be strictly related to social,
cultural and educational background, and, in the particular case of
elderly patients, to the ability to seek dental/oral medical services.
The latter aspect may provide a useful categorization of elderly
patients into three groups: a) functionally independent; b) in poor
health; and c) functionally dependent [13]. The majority of older
adults (95%) lives in the community: approximately 5% of these
are housebound and about 17% have major mobility limitations due
to chronic diseases [14], while 70% of the elderly population is able
to visit the dental office independently [15]. Among elderly people,
many factors have been identified as possible determinants in using
dental services, constituting a complex approach together with other
factors, particularly attitudinal considerations [16] (Table 1).
This paper provides a summary of common pathologic oral
conditions which occur in the hard and soft oral tissues in older
adults, and it emphasizes the importance for the general practitioner
to exchange information and cooperate with dentists in order to
improve patient care.
DISEASES OF ORAL HARD TISSUES

Dentition
External and internal tooth changes
Coronal and root surface caries

2010 Bentham Science Publishers Ltd.

620 Current Pharmaceutical Design, 2010, Vol. 16, No. 6

Tooth loss and sequels

Table 1. Determinants of the Uptake of Dental Services Among


the Elderly
Accessibility of the dental surgery
Availability of dental services (number of dentists and dental
hygienists)
Dental status (caries, number of teeth)
Gender
Personal characteristics
Perceived oral health, symptoms (pain)
Organization of the dental health care system (public, private)
Income
Cost of care
Social, cultural and geographical background
Ethnicity
Social relations
Lifestyle
General health status, functional disability, cognitive decline, number
and types of drugs used
Limitations of dentist

Periodontal Tissues
Gingivitis
Periodontitis
Tooth-alveolar abscess

Alveolar Bone
Atrophic mandible (Alveolar Bone loss, ABL)
Osteoporosis and Bisphosphonate-Related Osteonecrosis of
the Jaw (BRONJ)
Osteoradionecrosis and radiotherapy
Fracture

DENTITION
External and Internal Tooth Changes
Changes in dentition due to the ageing process can be attributed
to normal physiologic processes and to pathologic changes in
response to functional and environmental factors. External tooth
changes include discoloration (from yellow to brown) and enamel
loss due to abrasion, erosion or occlusal attrition [3] (Fig. 1a).
Thinning around the neck of teeth, often related to the use of hardbristled toothbrushes over many years of improper tooth brushing,
is frequently observed [17].
Severe enamel wear will ultimately expose underlying dentin,
which produces sclerotic and secondary dentin [18] in response to
trauma and caries. Over time, the number of blood vessels per tooth
and the thickness of the enamel are reduced, leading to decreased
sensitivity; dentin undergoes a reduction in thermal, osmotic, and
electrical sensitivity, and pain perception.
The susceptibility to caries decreases, the cementum (i.e. the
substance covering the root surface) gradually thickens and pulp

Guiglia et al.

dimensions are reduced [19-21]. Secondary dentin deposition,


pulpal calcifications, external root resorption, increased density and
volume of pulpal collagen fibers, and a diminished nerve supply are
factors that contribute to a progressive decrease in the pulp mass.
These age-related pulpal changes diminish tooth sensitivity and
pain perception, reduce responsiveness to pulp testing, and usually
decrease the need of local anaesthesia for dental procedures [22].
Coronal and Root Surface Caries
Dental caries causes tooth destruction due to the production of
acid by cariogenic bacteria (e.g. Streptococcus mutans,
Lactobacillus spp, and Actinomyces spp) to form dental plaque [23].
The available worldwide data show that dental caries is a major
public health problem in older people and closely linked to social
and behavioural factors [2,24]. Caries can be identified during a
visit to the dental surgeon and confirmed by dental x-rays: adult
subjects develop coronal caries (i.e. caries on the crown or enamel
surface), while the elderly people are also more susceptible to root
surface caries (i.e. caries on the root or cemental surface) due to
alveolar bone loss around the teeth. The cement is highly organic
and less resistant to environmental agents, such as sugar, acids from
soft drinks, and tobacco (known to have a drying effect) [25]. High
prevalence rates of coronal and root surface caries have been
identified among older populations in several countries worldwide
[2,26]: the incidence of root caries in patients over 60 years is twice
that of 30 year-olds [23], and 64% of people 80+ years have root
caries, and up to 96% have coronal caries [27].
In addition, elderly patients are more susceptible to root caries
due to inadequate oral hygiene, occasional dental examinations and
cleaning, salivary gland dysfunction, insufficient use of fluoridecontaining oral hygiene products and removable partial dentures,
which can trap plaque around the teeth, thereby favouring the
formation of caries. Root surface caries becomes more common in
the elderly because of periodontitis, local trauma, ABL, exposure of
root surfaces by gingival recession and periodontal pockets, and
insufficient removal of food/plaque between the teeth. Furthermore,
gastroesophageal acid reflux can encourage the formation of caries
via the action of acidic substances eroding the tooth structure, leaving a thinner layer of enamel or dentin which is more susceptible
to caries. The presence of caries is approximately asymptomatic in
the initial phases, but when the tooth's neurovascular structure
situated in the dental pulp is involved, sensitivity, pain, bacteraemia
and infection may occur [28].
Tooth Loss and Sequels
Recently, there has been a growing interest in the relationship
between the number of teeth and quality of life, considering not
only physical and functional implications but also social and
psychological factors [5,29]. Partial or total tooth loss is an agerelated condition that is caused primarily by severe dental caries
and periodontitis, thereafter leading to teeth extraction. An efficient
dentition plays an essential role in mastication, deglutition,
phonation, maintaining a balanced diet, aesthetical considerations
and facial expression. It has been suggested that ten occluding pairs
of teeth or twenty well-distributed teeth (shortened dental arch)
are appropriate for optimal masticatory performance [1,30,31]. On
the contrary, tooth loss is the main cause of reduced masticatory
efficiency (16%50%) [32], leading to difficulty in eating and food
selection [33]. Nonetheless, teeth perform other very important
functions:
they support the lips and cheeks;
they maintain an individual's vertical dimension of occlusion
(i.e. the relationship between the mandible and maxilla in
maximum closure/ intercuspidation);
together with the tongue and lips, they allow for the proper
pronunciation of various phonemes;

Aging and Oral Health

they preserve and maintain the height of the alveolar ridge;


they cut, grind, and otherwise chew food; and
as a result of their correct functioning, they assist in avoiding
nutritional deficiencies, social isolation and depression [34].
The treatment of total or partial edentulous arches requires
dental prostheses: fixed (e.g., bridges, implants) or removable
appliances. Fixed reconstructions offer greater stability and the
improved functions of chewing, swallowing, and speaking than
removable appliances, but they not provide the same stability and
proprioception of natural teeth. Both fixed and removable dentures
may be associated with many oral health problems, including
irritation, ulceration, gingival overgrowth, and pain. Since removable dentures are made of acrylic resin and the supporting
edentulous jawbones reabsorb progressively, these medical devices
must be monitored at least yearly to maintain stability and retention,
and to check for trauma to the mucosae. They also require special
attention as regards the removal of plaque in order to maintain oral
health. Teeth supporting partial dentures are most likely to develop
dental caries and gingivitis. Although there was no difference in the
proportion of men and women who lost all of their teeth, there were
large differences in the prevalence of edentulism by socioeconomic
status (6%78%) [24].
PERIODONTAL TISSUES DISEASES
Gingivitis
PD(s) are a heterogeneous group of diseases that affect the
supporting structures of the teeth (i.e. gingiva, root cement, alveolar
bone and periodontal ligament) and they are frequent both in
children and adults. Their aetiology is complex, clinical manifestations are different and several classification types have been proposed. In 1999 the American Academy of Periodontology classified
PD(s) in relation to aetiology [35] (during the International Workshop for a Classification of Periodontal Diseases and Conditions).
The majority of PD(s) occur or are aggravated by an accumulation
of dental plaque, which is a biofilm composed of approximately
500 species of microorganisms and their components (e.g.,
endotoxin, virulence factors) [36]; they develop on the surface of
teeth, leading to gingival inflammation labelled gingivitis. The
latter is characterized by erythema and edema of the gingiva, which
often bleeds easily after periodontal probing and gentle brushing or
even spontaneously (Fig. 1b). Although gingivitis is more common
in older persons, age alone is not a risk factor neither for gingivitis
nor periodontitis [23]. However, it is a reversible condition and if
treated with good oral hygiene the prognosis is good; alternatively
it may progress to periodontitis.
Periodontitis
Periodontitis (Fig. 1c) occurs when gingival inflammation
causes the periodontal ligament to detach from the cement, leading
to: the formation of gingival pockets and bone defects; tooth
migration; the development of diastemas between the loosening
teeth; increased mobility; abscesses; and finally tooth loss [37].
Periodontitis is associated with anaerobic bacteria, such as
Porphyromonas gingivalis, Bacteroides forsythus, and Aggregatibacter actinomycetemcomitans. Age-related immunologic changes
[38] and histological alterations in the periodontal tissue [39,40]
could alter the host response to dental plaque microorganisms,
affecting the patients susceptibility to periodontal disease, in
addition to the response to treatment. Nonetheless, changes in the
periodontal tissue that are ascribable exclusively to age are not
sufficient to lead to tooth loss, especially in a healthy adult [41,42].
Particular attention should be paid to the association between PD(s)
and cardiovascular diseases [43], as well as diabetes [44] and OP
[45]. Recent studies have also investigated the potential relationship
with rheumatoid arthritis [9], pancreatic cancer [10] and
Alzheimers disease [11,12]. For these reasons, it can be confirmed

Current Pharmaceutical Design, 2010, Vol. 16, No. 6

621

that the prevention, diagnosis and treatment of PD(s) are extremely


important in maintaining overall health during the ageing process.
Furthermore, several systemic conditions common among older
adults, as well as their treatments, have been linked with
periodontal disorders. Indeed, several classes of medications
frequently prescribed in older patients have been associated with
gingival overgrowth or other oral conditions [6,46,47]. Finally,
there exist socio-behavioural factors that influence the progression
of PD(s) in elderly people. Irregular dental visits, smoking,
psychosocial stress, and poor socioeconomic status are predictors of
periodontal attachment loss in older patients [48-51].
Tooth-Alveolar Abscess
In most circumstances, such as untreated caries, teeth fractures,
and chronic periodontitis, abscesses may develop, with pain and
destruction of the tooth-supportive structure. A tooth-alveolar
abscess is an acute lesion characterized by localization of pus and
swelling in the structures that surround the tooth, whose consequences may not be limited to the oral cavity due to the possible
spread of the infection through muscles and fascial planes. Pus is a
viscous fluid that usually contains white blood cells, dead tissue and
bacteria. Generally, the term tooth-alveolar abscess comprises 3
distinct processes (Fig. 1d):
1. Periapical abscess: originates in the periapical/periradicular
region due to bacteria deriving from a necrotic dental pulp,
usually secondary to dental caries. (Dental caries is very
common, eroding the protective layers of the tooth (i.e.
enamel, dentine and cement). The damage to the tooth allows
bacteria to invade the pulp, causing infection and necrosis);
2. Periodontal abscess: originates and involves the supporting
structures of teeth (i.e. gingiva, periodontal ligaments, bone
defects, gingival pockets);
3. Pericoronaritis: describes an infection of the gum that overlies
a partially erupted third molar.
When teeth are lost as a result of caries, the inflammatory
process can extend out to the root apex, infection spreading through
the bone and into soft tissue. Thus, untreated caries in older people
are associated with dental abscess and these infections are most
commonly combinations of obligate anaerobes such as the
Peptostreptococcus species, Porphyromonas gingivalis, Prevotella
intermedia, Prevotella melaninogenica and Fusobacterium
nucleatum.
ALVEOLAR BONE
Atrophic Bone Loss (ABL)
The alveolar bone (also known as the alveolar process) is a part
of the jaw that supports and anchors the dental roots. ABL represents the atrophy of the maxillary and mandibular bones, with a
reduction in bone height and volume. The atrophy of the jawbones
is age-related and its primary cause is periodontitis, although tooth
loss, the length of edentoulism, the pressure of wearing denture and
OP may be contributing factors. Reciprocally, ABL can contribute
to tooth loss [52].
Tooth and supporting bone loss reduce facial height, resulting
in a tendency toward prognathism, which may compromise the
patient's self-image. Tooth loss and ABL may interfere with the
patient's ability to eat, limiting dietary selection and compromising
nutrition. ABL and the resulting bone defects may contribute to the
progression of periodontitis and the occurrence of root caries,
causing additional tooth loss. In edentulous elderly patients,
alveolar bone resorption is accelerated, leaving a very reduced
alveolar ridge which can compromise removable denture retention
[52] (Fig. 2a).
Resorption is more pronounced in the mandible than in the
maxilla and there are many elderly people who do not wear their

622 Current Pharmaceutical Design, 2010, Vol. 16, No. 6

Guiglia et al.

Fig. (1). a) Diffuse caries associated with discoloration, b) Gingivitis, c) Chronic periodontitis d) Dento-alveolar abscess.

lower dentures as they find it very difficult to stabilize them [53]. In


particular, maxillary dentures with a significant loading surface area
on the hard palate can usually be fabricated and adjusted for
optimal fit, while mandibular dentures can be more probably
dislodged during speaking and chewing. The more appropriate
treatment for this problem is to prevent it by preserving natural
teeth or even roots and to construct appropriate prosthetic appliances (e.g., overdentures). The placement of dental implants and
biomedical devices placed within the bone seems to provide
functional stimulus to the bone and reduce bone loss [54]. In these
cases, endosseous titanium implants can be surgically placed in the
maxilla or mandible to support the dentures. The implant-supported
prostheses can provide a satisfactory chewing and speaking
capacity for many years while helping to prevent further ABL,
which is associated with wearing dentures without underlying
implant support. Dentures must be evaluated at least once a year to
ensure proper retention, stability, and mucosal health [55]. Dental
implants are used to replace single or multiple teeth or to serve as
abutments for fixed or removable prostheses with the goal of
restoring masticatory function and/or aesthetical considerations
[56]. Patients should take care in maintaining dental implants due to
the possibility of occurring perimplantitis, an inflammatory- mediated destruction of the bone around the implants caused by bacteria.
Osteoporosis and Bisphosphonate-Related Osteonecrosis of the
Jaw (BRONJ)
OP has been defined by the World Health Organization (WHO)
as a systemic skeletal disorder characterized by low bone mass and
microarchitectural deterioration of bone tissue, with a consequent
increase in bone fragility and susceptibility to fractures [57]. It
involves the stomatognathic apparatus with the same percentage of

the skeleton, and in several studies has been correlated with PD in


postmenopausal women and alveolar bone and tooth loss [58-60].
This phenomenon is expressed over a lifetime as increased cortical
porosity and a decreased density of cancellous bone [52]. Bisphosphonates (BPs) are the most frequently administered drugs for
the treatment and prevention of OP and the treatment of osteolytic
lesions in multiple myeloma, Pagets disease and bone metastases
associated with breast, prostate, lung, and other soft tissue tumors,
[61-64]. These medications suppress the actions of osteoclast s
and in this manner reduce bone resorption and increase bone
density. Cases of BRONJ have been reported in patients who take
BPs also for OP. BRONJ is a rare but serious condition,
characterized by trans-mucosal (intraoral) or transcutaneous (facial)
exposure of areas of maxillary or mandibular bone which is histopatologically characterized by avascular necrosis. Infection of the
exposed bone, abscess, fistulas, and pathologic fractures typically
complicate the clinical picture, leading the patient to suffer from
chronic pain and recurrent oro-facial infections [65,66]. No
satisfactory therapy is currently available and pain and infections
can only be controlled, requiring continuous medical care, multiple
courses of long-term antibiotics and analgesics [67-69].
BRONJ commonly follows oral surgical procedures, such as
tooth extraction, or other oral injury (e.g., trauma, dental pathologies), but spontaneous cases have also been reported (these have
tended to occur in patients wearing dentures, a potential source of
local trauma) [65,66]. Little is known about the aetio-pathogenesis
of BRONJ but the leading theory suggests that BRONJ may be
caused by cessation of bone remodelling and turnover. A pathogenetic model has suggested that BPs may inhibit angiogenesis in
the jaws, leading to a loss of blood vessels and vascular insuf-

Aging and Oral Health

ficiency with damage to microcirculation, a tendency to bone


ischemia and subsequent avascular necrosis [70].
Given that only a minority of BPs users develop bone necrosis,
other factors are likely to play a role in conferring susceptibility
(i.e. genetic predisposition, dysfunction of the coagulation system)
[71]. As a precaution, the American Dental Association (ADA)
recommends that patients who are prescribed BPs drugs receive a
thorough dental examination prior to beginning drug therapy, or as
soon as possible after beginning therapy. The ADA also recommends that patients who are taking oral BPs drugs should discuss
any potential risks from dental procedures (such as extractions and
implants) that involve the jawbone with their dentists [72].
Osteoradionecrosis and Radiotherapy
The mandible is one of the bones to be most frequently affected
by irradiation since in the majority of head and neck cancer patients
a large part is inevitably exposed to high doses of irradiation.
The most severe post-radiation late complication of the mandible is osteoradionecrosis (ORN). Contradictory data have been
reported regarding the incidence of this complication, its aetiology
and management. The incidence of mandibular ORN in head and
neck cancer patients, managed with radical or post-operative
irradiation, varies widely in the literature: from 0.4% to 56% [7377].
Although ORN typically occurs in the first three years after
radiotherapy, patients probably remain at indefinite risk. Indeed,
ORN is considered as late radiation damage to the Haversan bone
system and vessels characterized by inadequate repair and
repopulation [78,79]; radiation reduces the vascularization potential
of the tissues. The consequent hypovascular and hypoxic conditions
jeopardize cellular activity, collagen formation and wound healing
capacity [80,81]. Radiologic imaging of ORN has revealed
decreased bone density with possible fractures, cortical destruction
and loss of spongiosa trabeculation.
Numerous factors may be associated with the risk of ORN: a)
treatment-related variables (e.g. total radiotherapy dose, biologically effective dose, photon energy, rachytherapy dose rate, combination of external beam irradiation and interstitial brachytherapy,
field size, fraction size, volume of the mandible irradiated with a
high dose); b) patient-related variables (like deep periodontitis, preirradiation bone surgery, bad oral hygiene, alcohol and tobacco
abuse, bone inflammation, dental extraction after radiotherapy) and
c) tumor-related factors (tumor size or stage, proximity of the tumor
to bone, anatomic tumor site) [82].
In addition to anti-tumor effects, ionizing irradiation causes
damage in normal tissues located in the field of radiation. Oral
complications of radiotherapy in the head and neck region are the
result of the deleterious effects of radiation on salivary glands, oral
mucosa, bone, tooth, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include
mucositis, hyposalivation, loss of taste, ORN, radiation caries and
trismus. Mucositis and loss of loss are reversible consequences that
usually subside early on in the post-irradiation phase, while hyposalivation and its consequences (e.g., dryness of the mouth, burning
sensation, thirst, taste disturbances, difficulties in speech, chewing,
and swallowing, alterations in soft tissues, difficulties associated
with wearing dentures, a shift in oral microflora, noctu-rnal oral
discomfort, radiation caries, mucus accumulation and periodontal
disease) are normally irreversible [83].
Fracture
In severe cases of alveolar ridge atrophy, especially in the mandible, it is possible to experience significant problems in prosthesis
realization. The risk of mandibular fracture should also be considered due to its reduced load-bearing capability; mandible
fracture is a potential complication of BRONJ [84].

Current Pharmaceutical Design, 2010, Vol. 16, No. 6

623

DISEASES OF ORAL SOFT TISSUES AND SALIVARY


GLANDS

Oral and Pharyngeal Mucosa


Potentially malignant lesions (PML)
Cancer
Vesiculobullous diseases
Ulcerative diseases
Recurrent aphthous stomatitis (RAS)
Viral infections
Fungal infections
Bacterial infections

Salivary Glands
Obstructions
Hypofunction
Bacterial infectious
Neoplasia

Others
Burning mouth syndrome (BMS)

ORAL AND PHARYNGEAL MUCOSA


The clinical appearance of the oral and pharyngeal mucosae in
many healthy older persons is indistinguishable from that of
younger people. However, a lifelong history of oral mucosal trauma
(e.g., cheek biting), mucosal diseases (e.g., lichen planus), oral
habits (e.g., smoking), and salivary disorders (e.g., salivary
hypofunction) can modify this clinical aspect. Histologically, there
is evidence of epithelial thinning, decreased cellular proliferation,
loss of submucosal elastin and fat, and increased fibrotic connective
tissues with a degenerative alteration in collagen [85]. Clinically,
these structural changes may be accompanied by dry thin smooth
mucosal surfaces, with a loss of elasticity and stippling. These
changes may predispose the oral mucosa to trauma and infection,
particularly when they are associated with denture use and salivary
disorders. Oral mucosal immunity is believed to undergo various
age-related changes [38,85]. It is not known if advanced age per se
has a clinically significant adverse effect on the appearance and
function of the oral mucosae. However, the concomitant effects of
oral and pharyngeal mucosal diseases with age-related structural
and immunologic changes, local trauma, systemic diseases,
medications and poor nutritional status can cause significant oral
mucosal changes in an older adult [86]. Particularly, changes in oral
soft tissue that frequently occur in the ageing process are related to
subtle alterations in lip contours and in the mucosal lining of the
mouth, tongue and gum. Knowledge of these changes and knowing
what to look for in the mouth of elderly persons is the first step in
ensuring oral health during the ageing process.
Potentially Malignant Lesions (PML)
In 1978 the WHO proposed [87] that the precancerous lesions
of oral cavity be classified into two large groups, lesions and
conditions, with the following definitions:
a precancerous lesion is a morphologically-altered tissue in which
oral cancer is more likely to occur than its apparently normal
counterpart;
a precancerous condition is a generalized state associated with a
significantly increased risk of cancer.
In the latest workshop coordinated by the WHO Collaborating
Centre for Oral Cancer and Precancer on Head and Neck Tumours,
the term potentially malignant disorders [88] was recommended in

624 Current Pharmaceutical Design, 2010, Vol. 16, No. 6

order to indicate that not all lesions and conditions described under
the term precancerous may transform to cancer, but rather there is
a family of morphological alterations (e.g., epithelial precursors), of
which some may have an increased potential for malignant
transformation (Table 2) [89].
Table 2. Potentially Malignant Lesions of Oral Mucosa
Modified by Warnakulasuriya S. et al. [89].
Lesions

Conditions

Leukoplakia

Actinic keratosis

Erytroplakia

Lichen planus

Palatal lesions in reverse smokers

Discoid lupus erythematosus

Cancer
Oral cancer can occur more frequently in older individuals and
can affect the lips, gum tissues, cheek lining, tongue, hard and soft
palates, pharynx and floor of the mouth. Ninety-five percent of oral
and pharyngeal cancers occur after the age of 40 years [90], and
persons 65+ years are 7 times more likely to be diagnosed with oral
cancer than persons under 65 years of age [91]. Tobacco and
alcohol use are considered to be responsible for up to 75% of oral
cancers [92] but diets low in fruit and vegetables, the potential role
of the human papillomavirus (HPV), the influence of immunosuppression, genetic mutations and PML (primarily leukoplakia)
can all be implicated in these types of cancer [93]. Most oral and
oropharyngeal cancers are squamous cell carcinomas that arise
from the lining of the oral mucosae. PML and oral cancer can
appear as insignificant and asymptomatic lesions. A lesion may
begin as a white or red-colored patch, progress to ulceration, and
eventually become an endophytic or exophytic mass. Patients with
any white or red lesion that persists for longer than two weeks
should be referred to an oral medicine specialist for careful
evaluation [94].
Vesciculobullous Diseases
In the current PD(s) classification system, gingival manifestations of systemic conditions [35] have been included among nonplaque induced gingival disorders. Several mucocutaneous disorders and vesciculobullous diseases (i.e. lichen planus, pemphigoid,
pemphigus vulgaris, erythema multiforme, lupus erythematosus,
drug-induced lesions and others) are listed in this subgroup,
together with allergic reactions to dental materials, foods, and other
substances for topical application. Besides their heterogeneous
nature, all these disorders share two features: an immuno-mediated
pathogenesis and a possible common clinical manifestation, socalled desquamative gingivitis (DG). The term DG indicates the
presence of areas of atrophy, erythema, desquamation, erosion and
vesiculobullous lesions of the attached gingiva, of both anterior and
posterior areas, regardless of aetiopathogenesis. DG is a clinically
relevant entity as it can affect oral health and be a feature of
systemic disease [95].
Ulcerative Diseases
Compilato et al. [96] have proposed a new simple, complex
and destroying classification system (S-C-D system) in a recent
review for ulcers in clinical dental practice. Gingival ulcers have
various aetiologies and they may be due to, self-injury in
psychologically-disturbed or mentally-challenged patients, malignant neoplasms, drugs, dermatoses, or systemic diseases (e.g.,
hematological, mucocutaneous, gastrointestinal, or chronic infections such as tuberculosis, syphilis, mycoses, herpes viruses HIV)
[97].

Guiglia et al.

Recurrent Aphthous Stomatitis (RAS)


RAS is an oral ulcerative condition with an unknown
pathogenesis affecting people of any age. However, in about 80%
of cases the ulcerative episodes first appear before the age of 30 and
in particular during childhood. The frequency of RAS tends to
reduce with age whilst its severity increases [98]. The onset of
recurrent aphthosis in adults suggests a possible predisposing factor
underlying the disease or that the ulcerations are not simple
recurrent aphthosis, but a possible local sign of a more complex and
systemic disease [99]. For this reason, Scully [100] has suggested
that the term RAS should be reserved for ulcers in patients without
systemic diseases, while those with a similar clinical appearance
but associated with systemic disorders [101-105] should be
properly termed aphthous-like ulcers (ALU).
RAS is characterized by recurring, painful, solitary or multiple
ulcers, typically covered by a white-to-yellow pseudo-membrane
and surrounded by an erythematous area (Fig. 2b). RAS usually
involves non-keratinizing mucosae (e.g., labial mucosa, buccal
mucosa, ventral tongue) and three clinical forms have been
described: minor, major, and herpetiform. The minor form is the
most common and appears as rounded, well-demarcated, single or
multiple ulcers less than 1 cm in diameter, which usually heal in 10
to 14 days without scarring.
Viral Infectious
The most common viral infections are supported by the herpes
viruses. Oral zoster is caused by the reactivation of latent varicellazoster virus (VZV) infection. Initial infections typically occur in
childhood, the viruses then remaining latent in the sensory ganglia
until reactivation occurs secondary to immunosuppression, stress,
trauma, prolonged solar exposition, gastrointestinal disturbances or
concurrent infections. The clinical presentation in an older adult
will be similar to that in a younger person but lesions may persist
due to concomitant immunocompromised conditions. Shingles, a
VZV infection, is an acute condition with very painful and frequently incapacitating oral-facial lesions [106]. It is characterized by
a painful segmental eruption of small vesicles that rupture to form
confluent ulcers. Vesicles appear on skin and oral mucous
membranes, occurring unilaterally along the ophthalmic, maxillary,
or mandibular divisions of the trigeminal nerve.
Fungal Infectious
Although it is estimated that Candida spp are present in the
normal oral flora of healthy adults, some physiologic or pathologic
systemic conditions increase the risk of overgrowth in older persons
[107]. These conditions enhance the pathogenicity of individual
Candida spp, and they include local (e.g., xerostomia, denture
irritation, tobacco use, steroid inhaler use) and systemic (e.g.,
immunodeficiencies, systemic corticosteroid use, antibiotic use,
chemotherapy, radiation therapy, endocrine disorders, malabsorption, malnutrition) factors.
One of the most common changes to occur in the lips of elderly
persons is a condition called angular cheilitis (Fig. 2c). This is a
type of lesion that appears as skin folds with fissures at the corners
of the mouth and is primarily caused by candidiasis (fungal
infection) and a deficit of B vitamin. The presence of candidal
hyphae in oral smears indicates that the oral mucosal barrier has
been breached and that the patient is at risk of systemic infection.
Bacterial Infectious
The oral cavity contains more than 500 different bacterial
species [108]. Some of these, and more particularly Fusobacterium
nucleatum and black-pigmented anaerobic bacteria, can also be
found on other mucosal surfaces (e.g., gastrointestinal and genito-

Aging and Oral Health

Current Pharmaceutical Design, 2010, Vol. 16, No. 6

625

Fig. (2). a) Orthopantomogram showing marked resorption of the alveolar arches, b) Multiple ulcers in a case of RAS, c) Angular cheilitis

urinary tracts) [109,110]. The oral microbial flora is normally in


equilibrium, but related diseases can occur when the ecological
balance is compromised. The bacteria responsible for the most
common oral infections, PD(s) and dental caries are now better
known. The lesions caused by dental caries are associated with high
numbers of Streptococcus mutans and lactobacilli [111] while
Porphiromonas gingivalis, Bacteroides forsythus, Fusobacterium
nucleatum, Prevotella intermedia and Treponema denticola have
been associated with adult periodontitis, the most common form of
periodontitis [112]. Finally, Staphylococcus aureus and Streptococcus viridians support acute and chronic salivary infections.
SALIVARY GLANDS
Obstructions
Major and minor salivary glands may undergo degenerative and
obstructive alterations, bacterial infectious, hypofunction, and
neoplasia. Obstructive diseases of the major salivary glands
constitute an important chapter among the diseases of the head and
neck region. Due to the complex ductal system, salivary glands can
present several inflammatory diseases: sialadenitis (inflammation of
a salivary gland), sialodochitis (inflammation of a salivary duct),
sialoceles or ranula (an accumulation of saliva in subcutaneous
tissue due to a scratch in a salivary gland or duct), sialolithiasis
(formation of calculi in the salivary glands), all causing subsequent
obstruction [113-116]. The calculi can be single or multiple, round
or irregular with proximal, distal or intraglandular localization.
Although sialolithiasis may not elicit symptoms in some patients,
the intraductal stones, causing a mechanical obstruction of the
salivary duct with consequent stagnation of saliva, may cause
recurrent swelling during meals, which may be transient or
complicated by bacterial infections, associated with fever and pain
[116-118]. Recurrent or persistent ductal obstruction can lead to
chronic sialadenitis. Chronic or recurrent inflammation of the
submandibular gland could lead to the formation of a persistent
swelling (e.g., Kuttners tumour), which may easily be misdiagnosed for neoplasia [119].

Hypofunction
Saliva is a key element in oral homeostasis, oral function and
the maintenance of oral health. Saliva is involved in multiple
functions such as taste, mastication, deglutition, digestion,
maintenance of oral hard and soft tissues, control of oral microbial
populations, voice and speech articulation [120]. Reductions in
salivary flow (<500 mL in 24-hour) most commonly manifest as
symptoms of oral dryness [121]. It is important to distinguish
between two terms which are often erroneously used as synonyms
in clinical practice: a) xerostomia, indicating a subjective complaint
of a dry mouth; and b) hyposcialia, referring to objective alterations
in salivary performance, quantitative or qualitative, and thus to a
salivary gland dysfunction. Although xerostomia is most often
indicative of reduced salivary output, it is not invariably associated
with objective salivary gland hypofunction. Conversely, the
absence of symptoms of dry mouth is not a guarantee of adequate
salivary function.
Alterations in salivary function lead to a compromising of oral
tissues and functions and they can exert a great impact on a
patients quality of life. Furthermore, hyposalivation can increase
the risk of oral infection (e.g., candidiasis, dental caries, periodontal
disease and tooth loss) [120]. Patients with hyposalivation could
refer thirst, halitosis, dysphagia and, in particular, difficulties
associated with eating dry foods (such as biscuits), an intolerance to
acid and spicy foods, nocturnal oral discomfort, chronic oropharyngeal burning, mucus accumulation, food retention in the mouth, and
plaque accumulation [120,122]. Hyposalivation is common in older
people and its prevalence increases with age, involving
approximately 30% of patients aged 65+ years [123]. The highest
prevalence of hyposalivation in older people could be explained by
the increased incidence of medication use and systemic disease in
this group. Whilst more than 500 drugs have been implicated in
inducing salivary gland hypofunction, few of these have been
demonstrated to affect salivary function in controlled clinical
studies [124].

626 Current Pharmaceutical Design, 2010, Vol. 16, No. 6

Many systemic conditions can affect salivary function. Perhaps


the most important is Sjgren syndrome, a chronic autoimmune
disorder of the exocrine glands, primarily the salivary and lacrimal
glands, with associated lymphocytic infiltrates of the affected
glands [125,126]. The disease can occur in 2 forms: primary, which
involves the salivary glands, or secondary, which occurs along with
other autoimmune disorders mainly rheumatoid arthritis, systemic
lupus erythematosus or scleroderma. Xerostomia and xerophthalmia
are the main symptoms of primary Sjgren syndrome. Secondary
Sjgren syndrome also presents with symptoms of associated
systemic conditions. Indeed, this form may extend from an
autoimmune exocrinopathy to the manifestation of diverse extraglandular symptoms; the latter can involve the musculoskeletal,
pulmonary, gastrointestinal, hepatobiliary, hematological, vascular,
dermatological, renal, and nervous systems [125]. Deficiencies in
the quantity and quality of saliva have a negative impact on dental
and oral health. General discomfort is accompanied by problems in
swallowing, speaking, and alterations in taste, related to a lack of
saliva, in addition to photosensitivity, itching and fluctuating vision,
the latter probably related to a decreased ocular tear flow [127].
Other systemic conditions with associated salivary gland dysfunction include: cystic fibrosis, sarcoidosis, primary biliary cirrhosis,
poorly controlled diabetes, human immunodeficiency virus, graftversus-host disease, Epstein-Barr and hepatitis C virus infections,
and thyroid diseases. Rare causes of salivary gland dysfunction
include salivary gland agenesis, with or without ectodermal
dysplasia, triple-A syndrome, amyloidosis and hemochromatosis
[128]. Psychogenic causes, such as depression, anxiety, stress or
fear, can also result in xerostomia. In cases of Alzheimers disease,
patients may complain of dry mouth in the presence of normal
salivary secretion due to altered perception [120].
Bacterial Infections
Sialadenitis can arise from various infectious (viral and
bacterial) and non-infectious (obstructive salivary gland diseases,
Sjgrens syndrome, sarcoidosis, radiation therapy and various
allergens) causes. Bacterial sialadenitis principally affects the
parotid and submandibular glands and an acute and a chronic form
can be distinguished [129]. Acute suppurative sialadenitis is an
inflammatory and infectious process affecting principally debilitated and dehydrated elderly patients; indeed, this disease was a
well-documented complication of abdominal surgery prior to the
advent of antibiotics [130]. Autoimmune disorders, such as:
Sjgrens syndrome, drug-induced (e.g., antidepressant, anticholinergics, diuretics) decreased salivary flow, immunosuppression, diabetes and alcoholism, poor oral hygiene, and ductal
obstructions due to sialolithiasis or abnormalities of the ductal
system, tumour or foreign bodies may represent additional etiologic
factors. Of the infectious agents, most cases (80%) of acute
suppurative sialadenitis are due to Staphylococcus aureus, but
sialadenitis also may arise from Streptococci and anaerobes, such
as Peptostreptococcus spp and Bacteroides spp. [131].
Neoplasia
Salivary gland tumours are rare maxillofacial diseases with an
overall incidence in the western world of approximately 2.5-3.0 per
100,000 per year affected subjects between 50 and 70 years [132].
About 80% of all lesions are benign in nature, hence salivary
malignancies are particularly rare, comprising less than 0.5% of all
malignancies and about 5% are cancers of the head and neck. About
64 to 80% of salivary gland tumours develop in the parotid and,
fortunately, a relatively low percentage of parotid tumours are
malignant (range 15-32%). From 8 to 11% of all salivary tumours
occur in the submandibular gland, but the frequency of malignancy
in this gland is almost double than that of the parotid gland, ranging
from 37 to 45%. Few cases (no more than 1%) affect sublingual
glands and they are usually malignant [133,134]. Tumours of the
minor intra-oral salivary glands make up 9 to 23% of all tumours,

Guiglia et al.

which makes this group the second most common site for salivary
neoplasia; unfortunately, a relatively high proportion (almost 50%)
of these tumour are malignant [134]. Minor salivary gland tumours
are distributed in the upper aero-digestive tract, in the palate,
paranasal sinuses and nasal cavity, tongue, floor of the mouth, lips,
gingiva, pharynx, larynx and trachea. Most of them are intra-oral,
with the palate as the most frequent site followed by the lips,
causing a painless submucosal swelling. The mucosal layer is
frequently adherent to the mass, often showing ulceration [96].
OTHERS
Burning Mouth Syndrome
According to the International Association for the Study of
Pain, burning mouth syndrome (BMS) (i.e. stomatodynia,
glossodynia, oral dysaesthesia) has been defined as a "distinctive
nosological entity" characterized by "unremitting oral burning or
similar pain in the absence of visible oral mucosa changes" [135].
Furthermore, BMS refers to a chronic neurosensory disorder
usually unaccompanied by mucosal lesions or other clinical signs of
organic disease [136-138].
BMS is a relatively common condition with a prevalence in the
general population ranging from 0.7% to 15%, increasing with age
[139, 140]. Scala et al. [137] have proposed a classification of BMS
into two clinical forms: primary BMS or essential/idiopathic
BMS, for which organic local or systemic causes cannot be identified, probably originating in the activation of neuropathological
mechanisms; and secondary BMS, which would be the variant
resulting from local or systemic pathological conditions susceptible
to aetiology-directed therapy.
The aetiopathogenesis of primary BMS seems to be complex
and probably involves interactions among local environmental
factors (salivary gland dysfunction and altered mucosal blood
flow), the peripheral nervous system, central nervous system and
psychosocial factors [141]. New interesting associations have
recently emerged between BMS and peripheral nerve damage.
Lauria et al. [142] have suggested that BMS may be associated with
trigeminal small-fiber sensory neuropathy. Of note is the role of the
gustative innervation of the tongue in the pathophysiology of BMS
related to the peripheral nervous system. Femiano et al. [143] have
suggested that, as a result of the interaction between the
mechanisms of nociception and gustation in the central nervous
system, it is possible that BMS and other oral pain phantoms
result from damage to the gustatory system.
Finally, data have suggested the involvement of the central
nervous system and its interaction with the peripheral nervous
system in the pathogenesis of BMS [137]. Several conditions may
lead to secondary BMS: infections, allergic reactions, galvanism,
dental treatments, parafunctional habits, and salivary gland
dysfunction [144,145]. Moreover, hormonal disorders correlated to
the menopause, diabetes and nutritional deficiencies are systemic
conditions which probably influence the prevalence, onset, and
severity of BMS [137,140].
CONCLUSION
The oral cavity is involved in several physiologic activities
[55,129,130,132,133,136-145], such as language, posture, mastication, swallowing, prosthetic retention. It has been established that
the process of ageing includes a general progressive decline in the
bodys total skeletal musculature mass and its performance, which
includes masticators and mimic facial muscles. Thus the aging
process may lead to dramatic changes in the condition of teeth, oral
mucosae, alveolar bone and salivary glands, even if age alone does
not seem to play an exclusive role in these impairments. Dental,
periodontal, oral mucosal, and salivary diseases have a detrimental
and compounding affect on oral health in elderly persons, yet oral
disease is not necessarily a concomitant of growing older.

Aging and Oral Health

Similarly, numerous systemic diseases, drugs, and other medical


treatments can adversely affect oral functions in older adults. These
disorders must be recognized and managed appropriately by health
care practitioners who will be able to contribute to eradicating
disease, restoring function, and improving the quality of a persons
life.
In this context, geriatric dentistry plays a particularly important
role for the assessment and maintaining of conditions of beneficial
oral health in enhancing the quality of life of older patients. Routine
dental visits may help to reduce the incidence of many systemic
conditions, including cardiovascular diseases, diabetes, pneumonia
infections, and osteoporosis; the effects of stomatologic diseases are
not necessarily limited to the oral cavity, but oral pathogens can
directly (i.e. bacteremia) or indirectly (i.e. by complex immunologic pathways) cause these systemic conditions. Older edentulous
(i.e. no teeth) patients should undergo routine dental visits to
evaluate the status of soft tissue and the proper fitting of dentures. If
there are no acute conditions which need to be closely monitored, 6
months can be considered as an appropriate time interval for each
visit.
This paper is dedicated to geriatric doctors and dentists, as well
as to specialist of oral medicine in an attempt to summarize the
effects of aging in hard and soft oral tissues. According to the
WHO, the health of the mouth, teeth and associated structures and
their functions should be improved in the elderly; oral conditions
can have serious and disabling effects.
Obtaining dental care is different for the independent elderly
and those who are not institutionalized as compared to those who
are homebound. Moreover, accessibility, the organization of dental
care, and financial support for dental treatment are significant
factors that may influence the use of dental services (public,
private) among older people. Barriers to self-care and professional
care must be removed, prevention and early intervention strategies
must be formulated to reduce the risk of oral diseases. In some
communities, mobile dentists are available to visit homes and
nursing homes to provide dental care. This has increased the
number of elderly individuals who use dental services. Although a
certain portion of the elderly population does not regularly visit the
dentist, either because of personal choice or the inability to be
transported, about 60% who are dentate (i.e. with teeth) actually
have routine dental care, compared with 65% of younger individuals. On the other hand, only about 15% of elderly persons with
missing teeth make annual visits to the dentist. It is imperative to:
a) encourage older people to maximize their health and wellbeing
by looking after their dental and oral health; and
b) inform older people about the dental services available to them.
A dynamic assessment of these factors, in turn associated with
university programs of undergraduate and postgraduate training in
geriatric dentistry and oral and periodontal medicine, may be
important in increasing access to dental care by older people.

Current Pharmaceutical Design, 2010, Vol. 16, No. 6

VZV

Varicella-Zoster Virus

REFERENCES
[1]

[2]

[3]
[4]
[5]
[6]
[7]

[8]
[9]
[10]

[11]
[12]

[13]
[14]

[15]
[16]
[17]
[18]

[19]
[20]

ABBREVIATIONS
ADA
=
American Dental Association
ABL
=
Atrophic Bone Loss
BMS
=
Burning Mouth Syndrome
BPs
=
Bisphosphonates
BRONJ
=
Osteoporosis and Bisphosphonate-Related
Osteonecrosis of the Jaw
OP
=
Osteoporosis
ORN
=
Osteoradionecrosis
PD
=
Periodontitis
PML
=
Potentially Malignant Lesions
RAS
=
Recurrent Aphthous Stomatitis

627

[21]
[22]
[23]

[24]

[25]

Hildebrandt GH, Dominguez BL, Schork MA, Loesche WJ.


Functional units, chewing, swallowing, and food avoidance among
the elderly. J Prosthet Dent 1997; 77: 588-95.
Schou L. Oral health, oral health care, and oral health promotion
among older adults: social and behavioral dimensions. In: Cohen
LK, Gift HC, Eds. Disease Prevention and Oral Health Promotion.
Copenhagen: Munksgaard, 1995.
De Rossi SS, Slaughter YA. Oral changes in older patients: a
clinician's guide. Quintessence Int 2007; 38: 773-80.
Seymour GJ. "You cannot have good general health without good
oral health". N Z Dent J 2007; 103: 26-7.
Oral health related to general health in older people. Chap. 2.
Gerodontology 2005; 22: 9-11.
Ghezzi EM, Ship JA. Systemic diseases and their treatments in the
elderly: impact on oral health. J Public Health Dent 2000; 60: 28996.
Kuo LC, Polson AM, Kang T. Associations between periodontal
diseases and systemic diseases: a review of the inter-relationships
and interactions with diabetes, respiratory diseases, cardiovascular
diseases and osteoporosis. Public Health 2008; 122: 417-33.
Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol
1996; 1: 821-78.
Bartold PM, Marshall RI, Haynes DR. Periodontitis and rheumatoid
arthritis: a review. J Periodontol 2005; 76: 2066-74.
Michaud DS, Joshipura K, Giovannucci E, Fuchs CS. A prospective
study of periodontal disease and pancreatic cancer in US male
health professionals. J Natl Cancer Inst 2007 2007; 99: 171-5.
Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska
L, de Leon MJ. Inflammation and Alzheimer's disease: possible role
of periodontal diseases. Alzheimers Dement 2008; 4: 242-50.
Kamer AR, Dasanayake AP, Craig RG, Glodzik-Sobanska L, Bry
M, de Leon MJ. Alzheimer's disease and peripheral infections: the
possible contribution from periodontal infections, model and
hypothesis. J Alzheimers Dis 2008; 13: 437-49.
Ettinger RL, Beck JD. Geriatric dental curriculum and the needs of
the elderly. Spec Care Dentist 1984; 4: 207-13.
Leon J, Lai R. Functional status of the noninstitutionalized elderly:
estimates of ADL and IADL difficulties. National Medical
Expenditure Survey, research finding 4. Rockville: Agency for
Health Care Policy and Research, U.S. Department of Health and
Human Services 1990.
Ettinger RL. Oral health and the aging population. J Am Dent
Assoc 2007; 138: 5S-6S.
Holm-Pedersen P, Vigild M, Nitschke I, Berkey DB. Dental care
for aging populations in Denmark, Sweden, Norway, United
kingdom, and Germany. J Dent Educ 2005; 69: 987-97.
Gonsalves WC, Wrightson AS, Henry RG. Common oral
conditions in older persons. Am Fam Phys 2008; 78: 845-52.
Whittaker DK, Bakri MM. Racial variations in the extent of tooth
root translucency in ageing individuals. Arch Oral Biol 1996; 41:
15-9.
Drusini AG, Toso O, Ranzato C. The coronal pulp cavity index: a
biomarker for age determination in human adults. Am J Phys
Anthropol 1997; 103: 353-63.
Morse DR, Esposito JV, Schoor RS. A radiographic study of aging
changes of the dental pulp and dentin in normal teeth. Quintessence
Int 1993; 24: 329-33.
Ketterl W. Age-induced changes in the teeth and their attachment
apparatus. Int Dent J 1983; 33: 262-71.
Burke FM, Samarawickrama DY. Progressive changes in the pulpodentinal complex and their clinical consequences. Gerodontology
1995; 12: 57-66.
MacDonald DE. Principles of geriatric dentistry and their
application to the older adult with a physical disability. Clin Geriatr
Med 2006; 22: 413-34.
Petersen PE. The World Oral Health Report 2003: continuous
improvement of oral health in the 21st century--the approach of the
WHO Global Oral Health Programme. Commun Dent Oral
Epidemiol 2003; 31: 3-23.
Levy BM. Is periodontitis a disease of the aged? Gerodontology
1986; 5: 101-7.

628 Current Pharmaceutical Design, 2010, Vol. 16, No. 6


[26]
[27]

[28]
[29]
[30]

[31]
[32]

[33]
[34]
[35]
[36]

[37]
[38]

[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]

[49]

[50]
[51]

[52]
[53]
[54]
[55]

Vargas CM, Kramarow EA, Yellowitz JA. The oral health of older
Americans. Aging Trends 2001; 3: 1-8.
Warren JJ, Cowen HJ, Watkins CM, Hand JS. Dental caries
prevalence and dental care utilization among the very old. J Am
Dent Assoc 2000; 131: 1571-9.
Hahn CL, Liewehr FR. Innate immune responses of the dental pulp
to caries. J Endod 2007; 33: 643-51.
Locker D. Health outcomes of oral disorders. Int J Epidemiol 1995;
24: S85-9.
Steele JG, Ayatollahi SM, Walls AW, Murray JJ. Clinical factors
related to reported satisfaction with oral function amongst dentate
older adults in England. Commun Dent Oral Epidemiol 1997; 25:
143-9.
Witter DJ, van Palenstein Helderman WH, Creugers NH, Kayser
AF. The shortened dental arch concept and its implications for oral
health care. Commun Dent Oral Epidemiol 1999; 27: 249-58.
Heath MR. The effect of maximum biting force and bone loss upon
masticatory function and dietary selection of the elderly. Int Dent J
1982; 32: 345-56.
Krall E, Hayes C, Garcia R. How dentition status and masticator
function affect nutrient intake. JADA 1998; 129: 1261-9.
Kramarow E, Lentzner H, Rooks R, Weeks J, Saydah S. Health and
aging chartbook. Hyattsville, MD. Health United States: Center for
Health Statistics 1999.
Armitage GC. Development of a classification system for
periodontal diseases and conditions. Ann Periodontol 1999; 4: 1-6.
Paster BJ, Olsen I, Aas JA, Dewhirst FE. The breadth of bacterial
diversity in the human periodontal pocket and other oral sites.
Periodontol 2000 2006; 42: 80-7.
Ship JA, Beck JD. Ten-year longitudinal study of periodontal
attachment loss in healthy adults. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 1996; 81: 281-90.
Farthing PM, Walton LJ. Changes in immune function with age. In:
Squier CA, Hill MW, Eds. The effect of aging in oral mucosa and
skin. Boca Raton (FL): CRC press 1994: pp. 113-20.
Van der Velden U. Effect of age on the periodontium. J Clin
Periodontol 1984; 11: 281-94.
Fransson C, Berglundh T, Lindhe J. The effect of age on the
development of gingivitis. Clinical, microbiological and
histological findings. J Clin Periodontol 1996; 23: 379-85.
Burt BA. Periodontitis and aging: reviewing recent evidence. J Am
Dent Assoc 1994; 125: 273-9.
Persson RE, Persson GR. The elderly at risk for periodontitis and
systemic diseases. Dent Clin North Am 2005; 49: 279-92.
Beck JD, Pankow J, Tyroler HA, Offenbacher S. Dental infections
and atherosclerosis. Am Heart J 1999; 138: S528-S33.
Mealey BL. Periodontal disease and diabetes. A two-way street. J
Am Dent Assoc 2006; 137: 26S-31S.
Geurs NC, Lewis CE, Jeffcoat MK. Osteoporosis and periodontal
disease progression. Periodontol 2000 2003; 32: 105-10.
Meraw SJ, Sheridan PJ. Medically induced gingival hyperplasia.
Mayo Clin Proc 1998; 73: 1196-9.
Ciancio SG. Medications' impact on oral health. J Am Dent Assoc
2004; 135: 1440-8.
Genco RJ, Ho AW, Kopman J, Grossi SG, Dunford RG, Tedesco
LA. Models to evaluate the role of stress in periodontal disease.
Ann Periodontol 1998; 3: 288-302.
Beck JD, Sharp T, Koch GG, Offenbacher S. A study of attachment
loss patterns in survivor teeth at 18 months, 36 months and 5 years
in community-dwelling older adults. J Periodontal Res 1997; 32:
497-505.
Beck JD, Koch GG. Characteristics of older adults experiencing
periodontal attachment loss as gingival recession or probing depth.
J Periodontal Res 1994; 29: 290-8.
Axelsson P, Paulander J, Lindhe J. Relationship between smoking
and dental status in 35-, 50-, 65-, and 75-year-old individuals. J
Clin Periodontol 1998; 25: 297-305.
Bryant SR. The effects of age, jaw site, and bone condition on oral
implant outcomes. Int J Prosthodont 1998; 11: 470-90.
Klemetti E. A review of residual ridge resorption and bone density.
J Prosthet Dent 1996; 75: 512-4.
Carlsson GE. Responses of jaw bone to pressure. Gerodontology
2004; 21: 65-70.
Bryant SR, Zarb GA. Outcomes of Implant Prosthodontic
Treatment in Older Adults. J Can Dent Assoc 2002; 68: 97-102.

Guiglia et al.
[56]
[57]

[58]

[59]

[60]
[61]

[62]

[63]
[64]
[65]

[66]
[67]

[68]

[69]
[70]

[71]
[72]
[73]
[74]

[75]

[76]

[77]

[78]

Parameter on Placement and Management of the Dental Implant. J


Periodontol 2000; 71: S870-2.
Kanis JA, WHO Study Group. Assessment of fracture risk and its
application to screening for postmenopausal osteoporosis. Report of
a WHO Study Group. World Health Organization technical report
series 1994; 843: 1-129.
Jeffcoat MK, Lewis CE, Reddy MS, Wang CY, Redford M. Postmenopausal bone loss and its relationship to oral bone loss.
Periodontol 2000 2000; 23: 94-102.
Jonasson G, Bankvall G, Kiliaridis S. Estimation of skeletal bone
mineral density by means of the trabecular pattern of the alveolar
bone, its interdental thickness, and the bone mass of the mandible.
Oral Surg Oral Med Oral Pathol Oral Rad Endod 2001; 92: 346-52.
Krall EA, Dawson-Hughes B, Papas A, Garcia RI. Tooth loss and
skeletal bone density in healthy postmenopausal women.
Osteoporos Int 1994; 4: 104-9.
Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J,
et al. Zoledronic acid versus pamidronate in the treatment of
skeletal metastases in patients with breast cancer or osteolytic
lesions of multiple myeloma: a phase III, double-blind, comparative
trial. Cancer J 2001; 7: 377-87.
Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P,
Lacombe L, et al. A randomized, placebo-controlled trial of
zoledronic acid in patients with hormone-refractory metastatic
prostate carcinoma. J Nat Cancer Inst 2002; 94: 1458-68.
Major P. The use of zoledronic acid, a novel, highly potent
bisphosphonate, for the treatment of hypercalcemia of malignancy.
Oncologist 2002; 7: 481-91.
Van Poznak CH. The use of bisphosphonates in patients with breast
cancer. Cancer Control 2002; 9: 480-9.
Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated
osteonecrosis: a long-term complication of bisphosphonate
treatment. Lancet Oncol 2006; 7: 508-14.
Woo SB, Kalmar JR. Osteonecrosis of the jaws and
bisphosphonates. Alpha Omegan 2007; 100: 194-202.
Montebugnoli L, Felicetti L, Gissi DB, Pizzigallo A, Pelliccioni
GA, Marchetti C. Biphosphonate-associated osteonecrosis can be
controlled by nonsurgical management. Oral Surg Oral Med Oral
Pathol Oral Rad Endod 2007; 104: 473-7.
Campisi G, Di Fede O, Musciotto A, Lo Casto A, Lo Muzio,
Fulfaro F, et al. Bisphosphonate-related osteonecrosis of the jaw
(BRONJ): run dental management designs and issues in diagnosis.
Ann Oncol 2007; 18: vi168-72.
O'Neill PR, Hopeck J. Bisphosphonates and osteonecrosis of the
jaws: a primer for physicians for management and risk
identification. Iri Med J 2008; 101: 69-70.
Rizzoli R, Burlet N, Cahall PD, Delmas P, Eriksen EF, Felsenberg
D, et al. Osteonecrosis of the jaw and bisphosphonate treatment for
osteoporosis. Bone 2008; 42: 841-7.
Dannemann C, Zwahlen R, Gratz KW. Clinical experiences with
bisphopsphonate induced osteochemonecrosis of the jaws. Swiss
Med Wkly 2006; 136: 504-9.
Available from: http://www.ada.org/.
Murray CG, Herson J, Daly TE, Zimmerman S. Radiation necrosis
of the mandible: a 10 year study. Part I. Factors influencing the
onset of the necrosis. Int J Radiat Oncol Phys 1980; 6: 543-8.
Perez C, Purdy J, Breaux S, Ogura J, Von Essen C. Carcinoma of
the tonsillar fossa: a nonrandomized comparison of preoperative
radiation and surgery or irradiation alone: long term results. Cancer
1982; 50: 2314-22.
Schratter-Sehn AU, Handl-Zeller L, Strassl H, Braun OM,
Dobrowsky W. Incidence of osteoradionecrosis after combined
radiotherapy-chemotherapy of head and neck tumours. Strahlenther
Onkol 1991; 167: 65-8.
Miura M, Takeda M, Sasaki T, Inoue T, Nakayama T, Fukuda H,
et al. Factors affecting mandibular complications in low dose rate
brachytherapy for oral tongue carcinoma with special reference to
spacer. Int J Radiat Oncol Biol Phys 1998; 41: 763-70.
Dische S, Saunders M, Barrett A, Harvey A, Gibson D, Parmar M.
A randomized multicentre trial of CHART versus conventional
radiotherapy in head and neck cancer. Radiother Oncol 1997; 44:
123-36.
Kim JH, Chu FC, Pope RA, Woodard HQ, Bragg DB, Shidnia H.
Proceedings: Time dose factors in radiation induced osteitis. Am J
Roentgenoly Radium Ther Nucl Med 1974; 120: 684-90.

Aging and Oral Health


[79]

[80]
[81]
[82]
[83]

[84]

[85]
[86]

[87]

[88]

[89]
[90]
[91]

[92]
[93]
[94]
[95]
[96]

[97]
[98]

[99]
[100]
[101]

[102]

[103]

Makkonen TA, Kiminki A, Makkonen TK, Nordman E. Dental


extractions in relation to radiation therapy of 224 patients. Int J Oral
Maxillofac Surg 1987; 16: 56-64.
Perrier M, Moeller P. Osteoradionecrosis. A review of the
literature. Schweiz Monatsschr Zahnmed 1994; 104: 271-7.
Westermark A, Sindet-Pedersen S, Jensen J. Osteoradionecrosis,
pathogenesis, treatment and prevention. Tandlaegebladet 1990; 94:
669-73.
Jereczek-Fossa BA, Marsiglia HR, Orecchia R. Radiotherapyrelated fatigue. Crit Rev Oncol Hematol 2002; 41: 317-25.
Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral
sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med
2003; 14: 199-212.
Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related
osteonecrosis of the jaw: background and guidelines for diagnosis,
staging and management. Oral Surg Oral Med Oral Pathol Oral Rad
Endod 2006; 102: 433-41.
Williams DM, Cruchley AT. Structural aspects of aging in the oral
mucosa. The effect of aging in oral mucosa and skin. In: Squier CA,
Hill MW, Eds. Boca Raton (FL), CRC press, 1994; pp. 65-74.
Hill MW, Karthigasan J, Berg JH, Squier CA. Influence of age on
the response of oral mucosa to injury. In: Squier CA, Hill MW, Eds.
The effect of aging in oral mucosa and skin. Boca Raton (FL): CRC
press,1994: pp. 129-42.
World Health Organization. Collaborating Centre for, Oral
Precancerous lesions. Definition of leukoplakia and related lesions:
an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol
1978; 46: 518-39.
World, Health, Organization. World Health Organization
Classification of Tumours. In: Barnes L, Eveson JW, Reichart P,
Sidransky D, Eds. Pathology & Genetics Head and Neck Tumours.
Lyon: International Agency for Research on Cancer (IARC) IARC,
2005; pp. 177-9.
Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature
and classification of potentially malignant disorders of the oral
mucosa. J Oral Pathol Med 2007; 36: 575-80.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al.
Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106-30.
Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg
L, et al. SEER Cancer Statistics Review 1973-1997. Bethesda:
National Cancer Institute, 2000.
Weinberg MA, Estefan DJ. Assessing oral malignancies. Am Fam
Phys 2002; 65: 1379-84.
Silverman S. Oral cancer, 5th ed. Hamilton Ontario, Canada: BC
Decker, 2003.
National, Cancer, Institute. General information about lip and oral
cavity cancer. 2007; Available at: http://www.cancer.gov/
cancertopics/pdq/ treatment/lip-and-oral-cavity/patient.
Robinson NA, Wray D. Desquamative gingivitis: a sign of
mucocutaneous disorders--a review. Aust Dent J 2003; 48: 206-11.
Compilato D, Cirillo N, Termine N, Kerr AR, Paderni C, Ciavarella
D, et al. Long-standing oral ulcers: proposal for a new 'S-C-D
classification system'. J Oral Pathol Med 2009; 38: 241-53.
Coventry J, Griffiths G, Scully C, Tonetti M. ABC of oral health:
periodontal disease. BMJ 2000; 321: 36-9.
McCullough MJ, Abdel-Hafeth S, Scully C. Recurrent aphthous
stomatitis revisited; clinical features, associations, and new
association with infant feeding practices? J Oral Pathol Med 2007;
36: 615-20.
Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management
of recurrent aphthous stomatitis: a consensus approach. J Am Dent
Assoc 2003; 134: 200-7.
Scully C. Clinical practice. Aphthous ulceration. N Engl J Med
2006; 355: 165-72.
Campisi G, Compilato D, Cirillo N, Ciavarella D, Panzarella V,
Amato S, et al. Oral ulcers: three questions on their
physiopathology. Minerva Stomatol 2007; 56: 293-302.
Campisi G, Di Liberto C, Carroccio A, Compilato D, Iacono G,
Procaccini M, et al. Coeliac disease: oral ulcer prevalence,
assessment of risk and association with gluten-free diet in children.
Dig Liver Dis 2008; 40: 104-7.
Pastore L, Campisi G, Compilato D, Lo Muzio L. Orally based
diagnosis of celiac disease: current perspectives. J Dent Res 2008;
87: 1100-7.

Current Pharmaceutical Design, 2010, Vol. 16, No. 6


[104]

[105]
[106]
[107]
[108]
[109]
[110]
[111]

[112]
[113]
[114]

[115]
[116]
[117]

[118]
[119]
[120]
[121]

[122]
[123]
[124]
[125]
[126]
[127]

[128]
[129]

[130]
[131]
[132]
[133]

629

Field EA, Allan RB. Review article: oral ulceration-aetiopathogenesis, clinical diagnosis and management in the
gastrointestinal clinic. Aliment Pharmacol Ther 2003; 18: 949-62.
Scully C, Porter S. Oral mucosal disease: recurrent aphthous
stomatitis. Br J Oral Maxillofac Surg 2008; 46: 198-206.
Tenser RB. Herpes zoster infection and postherpetic neuralgia. Curr
Neurol Neurosci Rep 2001; 1: 526-32.
Samaranayake LP, Keung Leung W, Jin L. Oral mucosal fungal
infections. Periodontol 2000 2009; 49: 39-59.
Moore WE, Moore LV. The bacteria of periodontal diseases.
Periodontol 2000 1994; 5: 66-77.
Finegold SM, Strong CA, McTeague M, Marina M. The importance
of black-pigmented gram-negative anaerobes in human infections.
FEMS Immunol Med Microbiol 1993; 6: 77-82.
Hentges DJ. The anaerobic microflora of the human body. Clin
Infect Dis 1993; 16: S175-80.
Hardie JM. Oral microbiology: current concepts in the
microbiology of dental caries and periodontal disease. Br Dent J
1992; 172: 271-8.
Haffajee AD, Socransky SS. Microbial etiological agents of
destructive periodontal diseases. Periodontol 2000 1994; 5: 78-111.
Nahlieli O, Baruchin AM. Endoscopic technique for the diagnosis
and treatment of obstructive salivary gland diseases. J Oral
Maxillofac Surg 1999; 57: 1394-401.
Nahlieli O, Baruchin AM. Long-term experience with endoscopic
diagnosis and treatment of salivary gland inflammatory diseases.
Laryngoscope 2000; 110: 988-93.
Nahlieli O, Shacham R, Yoffe B, Eliav E. Diagnosis and treatment
of strictures and kinks in salivary gland ducts. J Oral Maxillofac
Surg 2001; 59: 484-90.
Marchal F, Dulguerov P. Sialolithiasis management: the state of the
art. Arch Otolaryngol Head Neck Surg 2003; 129: 951-6.
Roccia P, Di Liberto C, Speciale R, La Torretta G, Lo Muzio L,
Campisi G. Obstructive sialoadenitis: update of diagnosis and
therapy issues. Recent Prog Med 2006; 97: 272-9.
Roccia P, Di Liberto C, Speciale R, La Torretta G, Lo Muzio L,
Campisi G. Obstructive sialoadenitis: update of diagnosis and
therapy issues. Recent Prog Med 2006; 97: 272-9.
Tagnon B, Weynand B, Reychler H. Kuttner's tumour: a case
report. Acta Chir Belg 2008; 108: 621-4.
Gupta A, Epstein JB, Sroussi H. Hyposalivation in elderly patients.
J Can Dent Assoc 2006; 72: 841-6.
Porter SR, Scully C, Hegarty AM. An update of the etiology and
management of xerostomia. Oral Surg Oral Med Oral Pathol Oral
Rad Endod 2004; 97: 28-46.
Di Liberto C, Pizzo G, Di Fede O, Giannone N, Lo Muzio L,
Campisi G. Dysphagia in oral medicine. Recent Prog Med 2006;
97: 46-54.
Ship JA, Pillemer SR, Baum BJ. Xerostomia and the geriatric
patient. J Am Geriatr Soc 2002; 50: 535-43.
Ciancio SG. Medications impact on oral health. J Am Dent Assoc
2004; 135: 1440-8.
Delaleu N, Jonsson R, Koller MM. Sjogren's syndrome. Eur J Oral
Sci 2005; 113: 101-13.
Fox RI. Sjogren's syndrome. Lancet 2005; 366: 321-31
.Baudet-Pommel M, Albuisson E, Kemeny JL, Falvard F, Ristori
JM, Fraysse MP, et al. Early dental loss in Sjogren's syndrome.
Histologic correlates. European Community Study Group on
Diagnostic Criteria for Sjogren's Syndrome (EEC COMAC). Oral
Surg oral Med Oral Pathol 1994; 78: 181-6.
Hodgson TA, Shah R, Porter SR. The investigation of major
salivary gland agenesis: a case report. Pediatr Dent 2001; 23: 131-4.
Neville BW, Damm DD, Allen CM, Bouquot JE. Salivary Gland
Pathology. Oral Maxillofac Pathol 1st ed. Philadelphia: PA: W.B.
Saunders Co. 1995; pp. 327-9.
Fattahi TT, Lyu PE, Van Sickels JE. Management of acute
suppurative parotitis. J Oral Maxillofac Surg 2002; 60: 446-8.
Brook I, Jackson WE. Changes in the microbial flora of airline
headset devices after their use. Laryngoscope 1992; 102: 88-9.
Speight PM, Barrett AW. Salivary gland tumours. Oral Dis 2002 ;
8: 229-40.
Cawson RA, Odell EW. Neoplastic and non-neoplastic diseases of
salivary glands. Essentials of Oral Pathology and Oral Medicine. 6th
ed. Edinburgh: Churchill Livingstone 1998: p. 247.

630 Current Pharmaceutical Design, 2010, Vol. 16, No. 6


[134]

[135]

[136]
[137]
[138]

[139]

Neville BW, Damm DD, Allen CM, Bouquot JE. Salivary Gland
Pathology. Oral Maxillofac Pathol. 1st ed. Philadelphia, PA: W.B.
Saunders Co., 1995; pp. 336-9.
Merskey H, Bugduk N. Classification of chronic pain. Descriptions
of chronic pain syndromes and definitions of pain terms. In:
Merskey H, Bugduk N, Eds. Seattle, IASP: Report by the IASP
Task Force on Taxonomy 1994; p. 74.
Barker KE, Savage NW. Burning mouth syndrome: an update on
recent findings. Aust Dent J 2005; 50: 220-3.
Scala A, Checchi L, Montevecchi M, Marini I, Giamberardino MA.
Update on burning mouth syndrome: overview and patient
management. Crit Rev Oral Biol Med 2003; 14: 275-91.
Maltsman-Tseikhin A, Moricca P, Niv D. Burning mouth
syndrome: will better understanding yield better management? Pain
Pract 2007; 7: 151-62.
Boras VV, Brailo V, Lukac J, Kordic D, Blazic-Potocki Z. Salivary
interleukin-6 and tumor necrosis factor-alpha in patients with
burning mouth syndrome. Oral Dis 2006; 12: 353-5.

Received: October 1, 2009

Accepted: October 22, 2009

Guiglia et al.
[140]

[141]

[142]
[143]

[144]
[145]

Lamey PJ, Lamb AB. Prospective study of aetiological factors in


burning mouth syndrome. Br Med J (Clin Res Ed.) 1988; 296:
1243-6.
Patton LL, Siegel MA, Benoliel R, De Laat A. Management of
burning mouth syndrome: systematic review and management
recommendations. Oral Surg Oral Med Oral Pathol Oral Rad Endod
2007; 103: S39: e1-13.
Lauria G, Majorana A, Borgna M, Lombardi R, Penza P, Padovani
A, et al. Trigeminal small-fiber sensory neuropathy causes burning
mouth syndrome. Pain 2005; 115: 332-7.
Femiano F, Gombos F, Scully C. Burning Mouth Syndrome: open
trial of psychotherapy alone, medication with alpha-lipoic acid
(thioctic acid), and combination therapy. Med Oral 2004; 9: 8-13.
Sardella A. An up-to-date view on burning mouth syndrome.
Minerva Stomatol 2007; 56: 327-40.
Muzyka BC, De Rossi SS. A review of burning mouth syndrome.
Cutis 1999; 64: 29-35.