DENTOALVEOLAR SURGERY

Evaluation of the Efficacy of

Simvastatin in Bone Regeneration after
Surgical Removal of Bilaterally
Impacted Third Molars—A Split-Mouth
Randomized Clinical Trial
Saikrishna Degala, BDS, MDS (OMFS),* and Nikita A. Bathija, BDSy
Purpose: Simvastatin has been reported to promote osteoblastic activity, inhibit osteoclastic activity,
and support osteoblast differentiation induced by bone morphogenetic protein. This split-mouth random-
ized clinical trial evaluated the effect of local application of simvastatin (10 mg) on bone regeneration after
surgical removal of bilaterally impacted mandibular third molars.
Materials and Methods: A randomized, split-mouth, single-blinded, single-center trial was performed
in 30 patients 18 to 40 years old requiring surgical extraction of bilaterally impacted mandibular third mo-
lars. These patients underwent 2 surgical sessions, with extraction of 1 third molar during each session.
Each participant was randomly assigned to receive Gelfoam soaked with normal saline or with the drug
simvastatin (10 mg) at the first session and were blinded to the use of drug for that particular socket.
The alternate regimen was used during the second session. The study was conducted over a period of
3 months. Patients were evaluated for pain, postoperative swelling, and bone density measurement and
analysis using intraoral periapical radiographs at the end of 1, 4, 8 and 12 weeks, respectively. In addition,
cone-beam computed tomographic (CBCT) images were obtained for every fifth patient at the end of
12 weeks.
Results: Mean gray-level histographic values were significantly higher for the study sockets at the end of
1, 4, 8, and 12 weeks (P = .001) compared with the control sockets (30 sockets each). CBCT analysis
further substantiated accelerated bone regeneration in the study sockets.
Conclusion: The study was statistically and radiographically in favor of the drug, indicating that local
application of simvastatin could be a cost-effective and simple way to stimulate and hasten osseous regen-
eration.
Ó 2018 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 76:1847-1858, 2018

Third molar extraction is a very common procedure alveolar bone or ridge after extraction is ad-
performed in oral and maxillofacial surgery. Loss of vantageous.1
bone on the distal second molar is a common Bone regeneration is a complex process of bone
concern. Thus, preservation or augmentation of the formation similar to normal fracture healing and

Received from Department of Oral and Maxillofacial Surgery, JSS and Hospital (Constituent College), Jagadguru Sri Shivarathre, My-
Dental College and Hospital (Constituent College), Jagadguru Sri suru, Karnataka 570015, India; e-mail: drsaikrishnadegala@gmail.
Shivarathreeshwara University, Mysuru, Karnataka, India. com
*Professor and Head of Department. Received October 27 2017
yPostgraduate Student. Accepted April 25 2018
Conflict of Interest Disclosures: Neither author has a relevant Ó 2018 American Association of Oral and Maxillofacial Surgeons
financial relationship(s) with a commercial interest. 0278-2391/18/30419-1
Address correspondence and reprint requests to Dr Degala: https://doi.org/10.1016/j.joms.2018.04.035
Department of Oral and Maxillofacial Surgery, JSS Dental College

1847
1848
bone remodeling. Three essential components for
bone to successfully repair are osteoinduction, osteo-
genesis, and the osteoconductive matrix.2 Bone
morphogenic proteins (BMPs) are essential regulators
of osteogenic differentiation during bone repair.
BMP-2 causes multipotent stem cells to differentiate
into osteoblast-like cells.3 Use of inexpensive pharma-
cologic compounds, such as statins, to stimulate
autogenous bone growth factors could be a promising
approach for bone regeneration.
Gutierrez et al4 first reported that statins increased
BMP-2 expression in bone cells. Statins are frequently
used to lower cholesterol levels. Statins induce neoan-
giogenesis, cause stimulation of osteoblasts, decrease
vascular inflammation, are antithrombogenic, and in-
crease the expression of BMP-2 along with many other
osteoinductors.5,6
Various studies have analyzed the role of local
application of the drug simvastatin in bone regenera-
tion. Most of these studies have been carried out in
animals such as Wistar rats, New Zealand white rab-
bits, mice, and others.1,3,7-12 Almost all the trials
reported positive results not only for intraoral sites
but also for extraoral sites, such as cranial defects
and femur fractures. Trials also have been carried
out in humans for periodontal defects,13 periapical
cystic lesions,14 extracted premolar sockets15 and
osteoporosis in women.16 In vitro studies also have
been initiated to determine the exact mechanism of
action.5,17-19
Thus, this study investigated the management of
extracted mandibular third molar sockets using sim-
vastatin with Gelfoam as the carrier to enable bone
regeneration. The drug dosage was 10 mg, which
was chosen based on a literature review of
the drug.
Among statins, simvastatin has been studied
extensively and has pluripotent effects. Because me-
valonate, the result of a b-hydroxy b-methylglutaryl
and coenzyme A reductase response, is the fore-
runner for cholesterol and some other nonsteroidal
isoprenoid mixtures, hindrance of this key catalyst
can have pleiotropic effects. Simvastatin is a methyl
analogue of lovastatin and is synthesized by fermen-
tation of Aspergillus terreus. It is a nonhygroscopic
white crystalline powder that is insoluble in water
but quite soluble in chloroform, methanol, and
alcohol. Absorption of ingested doses of statins
varies from 40 to 75%. All have high first-pass
extraction by the liver. Most of the absorbed dose
is excreted in bile; 5 to 20% is excreted in urine.
Simvastatin is given orally at a dose of 20 to 40 mg
daily. The toxic dose of simvastatin is 160 mg.4
Statins decrease osteoclast formation through
apoptosis. A human study showed a decrease in
SIMVASTATIN FOR BONE REGENERATION
the number of bone fractures after statin
treatment.7
This study had the following aims and objectives:
 To assess the efficacy of simvastatin in bone regen-
eration after the surgical extraction of bilaterally
impacted third molars with a series of intraoral
periapical radiographs (IOPARs) at different inter-
vals during healing.
 To study and compare the rate of bone regenera-
tion in the socket using gray-scale histograms at
different intervals during healing.
 To evaluate and compare the clinical outcome
with and without the use of simvastatin using a
local anesthesia technique.
Materials and Methods
This study is a randomized, split-mouth, single-
blinded, single-center trial in 30 patients 18 to
40 years of age requiring surgical extraction of
bilaterally impacted mandibular third molars. The
participants were selected based on the following
criteria by purposive sampling from the outpatient
department of the authors’ university and the
entire process, from start to finish including
follow-up, was carried out by 1 maxillofacial
consultant.
INCLUSION CRITERIA
 Male and female patients
 Patients 18 to 40 years old
 Patients indicated for bilateral transalveolar
extraction of third molars
 Patients without any other systemic diseases or
comorbidities
FIGURE 1. Intraoperative placement of simvastatin.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral
Maxillofac Surg 2018.
DEGALA AND BATHIJA 1849

FIGURE 2. A, Preoperative right and left intraoral periapical radiographs. B, Postoperative intraoral periapical radiographs. (Fig 2
continued on next page.)
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.

EXCLUSION CRITERIA an informed consent before taking part in the examina-

 Presence of systemic illnesses
 Radiation therapy or chemotherapy to the head
and neck region
 Patients on long-term antibiotics or steroid ther-
apy
 Unwillingness to commit to a long-term follow-up
Preoperatively, bleeding time, clotting time, and
platelet count were measured and IOPARs or pano-
ramic radiographs were obtained. All patients signed
tion, which was reviewed and approved by the ethical
committee of the authors’ organization.
Each patient participated in 2 surgical sessions,
with extraction of 1 third molar during each session.
Patients were randomly assigned to receive Gelfoam
soaked with normal saline or Gelfoam soaked with
simvastatin at the first session (Fig 1). The alternate
regimen was used at the second session. Patients
were unaware as to which extracted site received
the drug intervention. Before the surgical procedure
for the study site, a 10-mg simvastatin tablet was
1850 SIMVASTATIN FOR BONE REGENERATION

FIGURE 2 (cont’d). C, Cone-beam computed tomogram of study socket. D, Cone-beam computed tomogram of control socket. Abbreviations:
C, control socket; S, study socket.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.

crushed and dispensed in 0.9% normal saline 2 mL.
The surgical procedure was carried out under aseptic
conditions after administration of local anesthesia.
The surgical site was closed using 3-0 black braided
silk. Regular postextraction instructions were given
to all patients. The following medications were pre-
scribed: amoxicillin clavulanate 625 mg twice daily
for 5 days, metronidazole 400 mg thrice daily for
3 days, and analgesics (nonsteroidal anti-
inflammatory drugs) twice daily for 3 days. All
patients were recalled on postoperative days 1 and
7 for follow-up study for review of pain and swelling.
IOPARs were taken at the end of 1, 4, 8, and
12 weeks, respectively, for bone density
DEGALA AND BATHIJA 1851

FIGURE 3. Assessment of digitized intraoral periapical radiographs. Arrow points to a marked area being measured and the histogram shows
the mean gray-scale value of the marked area on the grafted (simvastatin) side.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.

FIGURE 4. Assessment of cone-beam computed tomograms. Arrow points to a marked area being measured and the box shows the mean
gray-scale value of the marked area on the grafted (simvastatin) side.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.
1852
FIGURE 5. Descriptive statistics—gender.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral
Maxillofac Surg 2018.
measurement and analysis. Cone-beam computed
tomographic (CBCT) scanning was performed for
every fifth patient at the end of 12 weeks to further
analyze the efficacy of the drug (Fig 2).
EVALUATION OF PAIN
Pain intensity was evaluated using the visual analog
scale on postoperative days 1 and 7.
CLINICAL EVALUATION OF SWELLING
Preoperatively, swelling was calculated by
measuring a horizontal distance from the corner of
the mouth to the lobe of the ear and a vertical
distance between the outer canthus of the eye and
the angle of the lower jaw using silk suture following
the natural convexity of the patient’s face. The pro-
cedure was repeated on postoperative days 1 and 7.
The swelling was compared with the non-grafted
side to gauge whether simvastatin created additional
FIGURE 6. Descriptive statistics—age.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral
Maxillofac Surg 2018.
SIMVASTATIN FOR BONE REGENERATION
Table 1. DESCRIPTIVE STATISTICS—GENDER
Gender Frequency %
Women 14 46.7
Men 16 53.3
Total 30 100.0
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral
Maxillofac Surg 2018.
swelling in soft tissues other than the expected surgi-
cal swelling.
BONE DENSITY MEASUREMENT AND ANALYSIS
Bone regeneration was assessed with standard IO-
PARs taken using a parallel technique at the end of
1, 4, 8, and 12 weeks for each patient. All exposures
were performed at a standard of 70 kVp and 8 mA.
IOPARs were digitized using Epson Perfection V700
(Epson America, Inc, Long Beach, CA) and analyzed
using Adobe Photoshop CC (2015; Adobe Systems,
San Jose, CA) for gray-scale histographic values,
which indicated densities. Using preoperative radio-
graphs as guides, the area of the extracted third molar
socket was marked using the Magnetic Lasso Tool in
Photoshop CC. The image parameters were standard-
ized and applied for subsequent radiographs at post-
operative weeks 1, 4, 8, and 12 for all patients. The
mean gray-scale values of the extracted socket in
the 2 groups were measured using the Histogram
Tool in Photoshop CC (Fig 3). These values were
recorded in a similar manner for all patients. CBCT
images were analyzed using CS 3D Imaging software
(Carestream Dental, Atlanta, GA) using the curved
slicing option in the coronal plane at a section thick-
ness of 9.9 mm (Fig 4).
All data were transferred to Excel (Microsoft,
Redmond, WA) sheets for ease of comparison
and statistical assessment was performed
using SPSS 20.0 for Windows (IBM Corp,
Armonk, NY). The statistical methods that were
applied to obtain the results included descriptive
statistics, c2 test, cross-tabulations (Cramer V),
Table 2. DESCRIPTIVE STATISTICS—AGE
Age (yr) Frequency %
<20 2 6.7
21-25 19 63.3
26-30 6 20.0
$30 3 10.0
Total 30 100.0
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral
Maxillofac Surg 2018.
DEGALA AND BATHIJA 1853

FIGURE 7. Comparison of pain. CS, control socket; SS, study socket; VAS, visual analog scale.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.

paired-samples t test, repeated measures analysis of
variance, and contingency coefficient analysis
(cross-tabulations).
Results
Of the 30 patients, 16 (53.3%) were men and
14 (46.7%) were women. The patients’ mean age
was 31.5 years (range, 21 to 25 yr; Figs 5,
6, Tables 1,2).
Paired t test showed no relevant difference in mean
values for pain between the study and control groups
from day 1 to day 7. Comparison of postoperative
swelling on postoperative day 1 showed a mild in-
crease horizontally for the study side (mean, 10.67),
but no relevant difference was noted on postoperative
day 7. No relevant difference was found in the vertical
dimension (Figs 7, 8, Tables 3,4).
The mean gray-level histographic values at the end
of the first postoperative week for the study and con-
trol sockets were 70.04  6.4 (minimum, 60.21;
maximum, 79.63) and 66.3  6.1 (minimum, 56.41;
maximum, 76.33), respectively.
The mean values increased to 82.00  6.5 (mini-
mum, 71.12; maximum, 91.1) and 77.41  6.01
(minimum, 67.41; maximum, 85.55)for the study
and control sockets, respectively, at the end
of 4 weeks.
The mean values increased to 92.18  4.7 (mini-
mum, 80.66; maximum, 98.64) and 86.70  4.6

FIGURE 8. Comparison of postoperative swelling. Abbreviations: CS, control socket; SS, study socket.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.
1854 SIMVASTATIN FOR BONE REGENERATION

Table 3. PAIRED-SAMPLES STATISTICS—PAIN

difference between the study and control sockets
(P = .001) in favor of the study socket (Fig 10, Table 8).
Mean n SD SEM

Pair 1 Discussion
ss_vas_1postop 2.9333 30 0.69149 0.12625
Bone possesses an intrinsic capacity for regenera-
cs_vas_1postop 2.6667 30 0.71116 0.12984
Pair 2 tion. Inducing bone growth has a wide range of clinical
ss_vas_7postop 0.2333 30 0.43018 0.07854 applications and the value of its induction has
cs_vas_7postop 0.1667 30 0.37905 0.06920 increased in maxillofacial surgery.17
The extraction of teeth is the most common
Abbreviations: cs, control socket; gs, gray-scale or gray-level procedure carried out by a maxillofacial practitioner,
histographic values; postop, postoperative day; SD, standard
deviation; SEM, standard error of the mean; ss, study socket; and the extraction of mandibular third molars is most
vas, visual analog scale. common owing to its various eruption patterns. The
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral extraction sockets heal slowly by secondary intention
Maxillofac Surg 2018. with remodeling up to 1 year after the procedure.20
During this time, approximately 0.5 mm of bone
resorption can occur. In consequence, preservation
(minimum, 76.59; maximum, 92.11) for the study or augmentation of the alveolar bone or ridge
and control sockets, respectively, at the end becomes essential. The process of bone formation
of 8 weeks. involves growth factors such as BMP-2. Many bone-
After 12 weeks, the mean values were 110.46 (min- inducing techniques have been investigated and
imum, 100.32; maximum, 120.42) in the study group each has pitfalls.15,20
and 99.94 (minimum, 90.12; maximum, 110.31) in Many investigators have reviewed the role of sta-
the control group (Tables 5,6). tins in switching on genes for osseous formation,
A statistically significant difference was present with great potential in bone grafting in the cra-
between the 2 groups with an increase in mean niofacial region. The emphasis was shifted to
gray-level histographic values at the end of 1, 4, 8, their osteoinductive properties by the research of
and 12 weeks (P = .001). At every step, markedly Gutierrez et al.4,15
higher values were observed in the study group Simvastatin has been proved to stimulate osteo-
(Fig 9, Table 7). blastic differentiation and mineralization in nontrans-
Analysis of CBCT images substantiated the acceler- formed osteoblastic cells in vitro and in vivo in rats
ated bone regeneration in the study sockets. The and rabbits. It also markedly increases mRNA expres-
mean gray-scale value of the study socket was 179.0 sion for alkaline phosphatase, type I collagen, bone
compared with 125.67 for the control socket. After sialoprotein, and osteocalcin in nontransformed oste-
applying paired t test, there was a significant oblastic cells and decreases gene expression for

Table 4. PAIRED-SAMPLES STATISTICS—SWELLING

Mean n SD SEM df Significance (2-tailed)

Pair 1
ss_hor_SWL_1postop 10.6667 30 1.48819 0.27171 .001
cs_hor_SWL_1postop 9.9400 30 1.37329 0.25073 29
Pair 2
ss_ver_SWL_1postop 9.7967 30 1.24886 0.22801 .541
cs_ver_SWL_1postop 9.7633 30 1.21895 0.22255 29
Pair 3
ss_hor_SWL_7postop 9.6667 30 1.33011 0.24284 .018
cs_hor_SWL_7postop 9.4767 30 1.26291 0.23058 29
Pair 4
ss_ver_SWL_7postop 8.8200 30 1.22006 0.22275 .012
cs_ver_SWL_7postop 9.0167 30 1.22392 0.22346 29
Abbreviations: cs, control socket; df, degrees of freedom; hor, horizontal; postop, postoperative day; SD, standard deviation;
SEM, standard error of the mean; ss, study socket; SWL, swelling; ver, vertical.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.
DEGALA AND BATHIJA 1855

Table 5. MEAN GRAY-LEVEL HISTOGRAPHIC VALUES (INTRAORAL PERIAPICAL RADIOGRAPHS)—STUDY SIDE

Mean SD n F Significance

ss_gs_w1postop 70.0387 6.41470 30 1,249.66 .001

ss_gs_w4postop 82.0027 6.54098 30
ss_gs_w8postop 92.1793 4.73756 30
ss_gs_w12postop 110.4563 6.70809 30
Abbreviations: gs, gray-scale or gray-level histographic values; postop, postoperative; SD, standard deviation; ss, study socket; w,
week.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.

collagenase-1 and collagenase-3.6,15,18 Some studies
have found that simvastatin suppresses osteoclasts,
thus promoting bone repair.7 Vascular endothelial
growth factor (VEGF) is not only an intense angio-
genic factor but also a vital particle for bone develop-
ment, suggesting that statin-actuated VEGF could
assume a part in angiogenesis and osteogenesis.3,21
Simvastatin also improves trabecular bone density
and promotes and hastens early consolidation and
mineralization.6,8,22
Statins undergo high first-pass metabolism and
increasing the dose of systemic statins can cause liver
failure, kidney disease, and rhabdomyolysis.5 Subcu-
taneous injection of simvastatin was found to be irrel-
evant to osseous generation. Conversely, local
administration was suggested to deliver simvastatin
directly in therapeutic concentrations for bone forma-
tion with virtually no side effects.6,15 In this trial, a
dosage of 10 mg was standardized for all participants
and no adverse effects were observed.
Gutierrez et al4 concluded that topical application
of statin was 50 times more active in bone formation
in rats than oral administration. In addition, several
studies have used simvastatin with carriers, such as
the gelatin sponge,6,9,10,15 collagen sponge,11 collagen
matrix,23 poly(lactic-co-glycolic acid),13,19,24 methyl
cellulose gel,13,25 a-tricalcium phosphate rods,1,8 and
biodegradable hydrogel,26 for successful local delivery.
In this study, gelatin sponge was the carrier of
choice because of its biocompatibility. In addition, it
is bioresorbable and conforms easily to the shape of
bone defects. Moreover, with its slow resorption
rate, it enabled slow and sustained release of simva-
statin to maximize its effect on osseous regeneration.
Nearly all studies on the topical application of simva-
statin on bone defects have indicated positive re-
sults.6,8-10,13,15,16,23 Wong and Rabie23 used
simvastatin for parietal bone defects and found 308%
more new bone in defects grafted with simvastatin.
In another study, simvastatin was locally applied to
mandibular bone defects, resulting in 240% greater
density in the experimental group.10
Nevertheless, there were studies that were contradic-
tory in the beneficial effects of simvastatin on bone
regeneration. Pauly et al24 reported impaired integration
of simvastatin-coated intramedullary titanium implants
after 8 weeks of healing in rat femurs. Similarly, Lima
et al12 combined simvastatin with demineralized bovine
bone matrix for repairing rat calvarial defects, with un-
desirable results after 30 to 60 days of healing.
The present study used a randomized, split-mouth,
single-blinded study to determine the efficacy of local
application of simvastatin in bone regeneration after
surgical extraction of bilaterally impacted mandibular
third molars. The results showed a marked increase
in mean gray-level histographic values of the study
socket compared with the control socket (30 sockets
each). These values were successively higher for the
study site at the end of 1, 4, 8, and 12 weeks, with a
drastic increase in gray-level histographic values for
the study socket at the end of 8 and 12 weeks. These
results corresponded with those of Chauhan et al5

Table 6. MEAN GRAY-LEVEL HISTOGRAPHIC VALUES (INTRAORAL PERIAPICAL RADIOGRAPHS)—CONTROL SIDE

Mean SD n F Significance

cs_gs_w1postop 66.3300 6.09858 30 939.42 .001

cs_gs_w4postop 77.4197 6.00742 30
cs_gs_w8postop 86.7033 4.61901 30
cs_gs_w12postop 99.9357 4.55367 30
Abbreviations: cs, control socket; gs, gray-scale or gray-level histographic values; postop, postoperative; SD, standard deviation;
w, week.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.
1856 SIMVASTATIN FOR BONE REGENERATION

FIGURE 9. Comparison of gray-level histographic values in study and control sockets (intraoral periapical radiographs). Abbreviations: CS,
control socket; SS, study socket.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.

and Saifi et al.15 Moreover, CBCT scanning for every
fifth case at the end of 12 weeks supported the posi-
tive role of simvastatin in osseous regeneration.
The authors also evaluated facial swelling in the
study and control groups on postoperative days 1
and 7. The values of facial swelling were numerically
higher on the study side than on control side on post-
operative day 1, which subsided by postoperative day
€
7. Similar findings were reported by Ozeç et al.10
8
Nyan et al found that simvastatin combined with cal-
cium sulfate caused substantial bone regeneration in
rat calvarial defects with considerable soft tissue
inflammation. Hence, simvastatin acts locally depend-
ing on the dose and the carrier.
The present results are reinforced by those of
Maciel-Oliveira et al9 and Griffiths and Cartmell27
who advocated that simvastatin induces osseous
regeneration when topically injected into defects
made in the rat alveolar region. This was supported
with ultrastructural and immunocytochemical studies.
The present study also is supported by the study
conducted by Ayukawa et al7 who found that the effect
of local administration of simvastatin hastened the
healing of artificially created bone defects. Mouhamed
et al14 in their human study concluded that digital
radiologic examination and histologic analysis proved
that adding tricalcium phosphate to simvastatin
improves bone formation.

Table 7. PAIRED-SAMPLES STATISTICS: MEAN GRAY-LEVEL HISTOGRAPHIC VALUES—INTRAORAL PERIAPICAL

RADIOGRAPHS

Mean n SD SEM df Significance (2-tailed)

Pair 1
ss_gs_w1postop 70.0387 30 6.41470 1.17116 29 .001
cs_gs_w1postop 66.3300 30 6.09858 1.11344
Pair 2
ss_gs_w4postop 82.0027 30 6.54098 1.19421 29 .001
cs_gs_w4postop 77.4197 30 6.00742 1.09680
Pair 3
ss_gs_w8postop 92.1793 30 4.73756 0.86496 29 .001
cs_gs_w8postop 86.7033 30 4.61901 0.84331
Pair 4
ss_gs_w12postop 110.4563 30 6.70809 1.22472 29 .001
cs_gs_w12postop 99.9357 30 4.55367 0.83138
Abbreviations: cs, control socket; df, degrees of freedom; gs, gray-scale or gray-level histographic values; postop, postoperative;
SD, standard deviation; SEM, standard error of the mean; ss, study socket; w, week.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.
DEGALA AND BATHIJA
FIGURE 10. Comparison of gray-level histographic values in study and control sockets (cone-beam computed tomograms). Abbreviations: CS,
control socket; SS, study socket
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral Maxillofac Surg 2018.
The present results also are in accord with those of
Chauhan et al6 who documented the affirmative use of
simvastatin in bone regeneration in extracted third
molar sockets. Similar results were found by Saifi
et al15 who used simvastatin in extracted maxillary
and mandibular premolar sockets.
To the best of the authors’ knowledge, this study is
the first to use CBCT imaging as an evaluation param-
eter to assess bone density after treating the bony
defect with simvastatin.
Complications, such as dry socket, infection, or
draining sinus, were not observed during the follow-
up period, suggesting that simvastatin is well tolerated
by patients and is safe for local application.
The present results were statistically and radio-
graphically in favor of the topical use of simvastatin.
However, the present study is limited by its small sam-
ple and short duration of follow-up. Likewise, histolog-
ic analysis should be performed to assess the quality of
newly formed bone. Additional research is needed to
determine the optimal therapeutic threshold, mode
Table 8. PAIRED-SAMPLES STATISTICS: MEAN GRAY-
LEVEL VALUES—CONE-BEAM COMPUTED TOMOGRA-
PHY
Significance
Pair 1 Mean n SD SEM df (2-tailed)
ss_coronal_12w 179.00 6 1.414 0.577 5 .001
cs_coronal_12w 125.67 6 1.211 0.494
Abbreviations: cs, control socket; df, degrees of freedom; SD,
standard deviation; SEM, standard error of the mean; ss,
study socket; w, week.
Degala and Bathija. Simvastatin for Bone Regeneration. J Oral
Maxillofac Surg 2018.
1857
of application, and effectiveness of osseous regenera-
tion in humans.
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