See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/5622278

Influence of estrogen deficiency and its

treatment with alendronate and estrogen on
bone density around osseointegrated...

Article in Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology · March 2008
DOI: 10.1016/j.tripleo.2007.06.010 · Source: PubMed

CITATIONS READS

52 78

6 authors, including:

Gabriela Giro Celso Eduardo Sakakura

Universidade Guarulhos Centro Universitário da Fundação Educacio…
50 PUBLICATIONS 491 CITATIONS 25 PUBLICATIONS 372 CITATIONS

SEE PROFILE SEE PROFILE

Rosa Maria Rodrigues Pereira Silvana R P Orrico

Hospital das Clínicas da Faculdade de Medi… São Paulo State University
143 PUBLICATIONS 1,117 CITATIONS 75 PUBLICATIONS 595 CITATIONS

SEE PROFILE SEE PROFILE

All content following this page was uploaded by Gabriela Giro on 31 January 2017.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.
Influence of estrogen deficiency and its treatment with
alendronate and estrogen on bone density around
osseointegrated implants: radiographic study in
female rats
Gabriela Giro, DDS, MSc,a Daniela Gonçalves, DDS, MSc,b
Celso Eduardo Sakakura, DDS, MSc, PhD,c Rosa Maria Rodrigues Pereira, MD, PhD,d
Elcio Marcantonio Júnior, DDS, MSc, PhD,e and
Silvana Regina Perez Orrico, DDS, MSc, PhD,f São Paulo, Brazil
STATE UNIVERSITY OF SÃO PAULO AND UNIVERSITY OF SÃO PAULO

Objective. This study evaluated the influence of estrogen deficiency and its treatment on bone density around
integrated implants.
Study design. Implants were placed in female rat tibiae. The animals were assigned to 5 groups: control, sham,
ovariectomy, estrogen, and alendronate. The control group was humanely killed to confirm integration of the implant.
The others were submitted to ovariectomy or sham surgery. Bone density was measured by digital radiographs at 6
points on sides of the implant.
Results. The analysis of radiographic bone density revealed estrogen privation had a negative impact only in the
cancellous bone. The estrogen group differed significantly (P ⬍ .05) from the ovariectomy and alendronate groups.
The alendronate group presented the highest density for all evaluated regions.
Conclusion. Ovariectomy caused a decrease in the radiographic bone density in the cancellous region. Estrogen
replacement therapy and alendronate were effective treatments in preventing bone mass loss around integrated
implants. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:162-7)

Osseointegrated implants represent an important alter-
native for the rehabilitation of partially or totally eden-
tulous patients. Nevertheless, systemic alterations, such
as osteoporosis, have been reported as factors poten-
tially related to unsuccessful osseointegration. There-
fore, it has been suggested that these systemic disorders
might severely compromise the success of dental im-
plants placed in osteoporotic patients.1
Osteoporosis is an osteometabolic disease that com-
monly affects postmenopausal women as a result of the
decrease in estrogen levels secondary to the loss of
ovarian function.2 Estrogen deficiency increases bone
turnover, which results in a high bone remodeling rate
in which bone resorption exceeds bone formation. As a
result of excessive resorption, the trabecular bone is
compromised.3,4 This process leads to a decrease in
bone mass, which, in turn, results in greater bone fra-
gility and increased risk of fractures.
Several authors5-7 have investigated the role of os-
teoporosis and its treatments on the period of dental
implant healing. It has been reported that drugs cur-
rently used for osteoporosis control are effective in
prevention of bone loss around recently placed im-
plants. However, there are few reports about the effect
of osteoporosis on dental implants that are already
osseointegrated. In view of this, the purpose of the
present study was to evaluate the influence of ovariec-
tomy-induced estrogen deficiency and its treatment

This study was supported by a grant-in-aid from Brazilian agencies
for research support (The State of São Paulo Research Foundation
[FAPESP] and the Coordination for Improvement of Higher Educa-
tion Personnel [CAPES]). The authors are grateful to AS Technology
for supplying the microimplants used in this study.
a f
PhD Student, Periodontics Program, Department of Oral Diagnosis
and Surgery, School of Dentistry of Araraquara, UNESP—São Paulo
State University.
b
PhD Student, Periodontics Program, Department of Oral Diagnosis
and Surgery, School of Dentistry of Araraquara, UNESP—São Paulo
State University.
c
Associate Professor, Barretos Dental School, Barretos Educational
Foundation.
d
Associate Professor, Department of Rheumatology, School of Med-
icine, University of São Paulo.
e
Adjunct Professor, Department of Oral Diagnosis and Surgery,
School of Dentistry of Araraquara, UNESP—São Paulo State Uni-
versity.
Adjunct Professor, Department of Oral Diagnosis and Surgery,
School of Dentistry of Araraquara, UNESP—São Paulo State Uni-
versity.
Received for publication Mar 12, 2007; returned for revision May 19,
2007; accepted for publication Jun 5, 2007.
1079-2104/$ - see front matter
© 2008 Mosby, Inc. All rights reserved.
doi:10.1016/j.tripleo.2007.06.010

162
OOOOE
Volume 105, Number 2
Fig. 1. Study experimental protocol.
with alendronate and estrogen on the density of the
bone tissue surrounding titanium implants 60 days after
implant placement.
METHODS
The study protocol was approved by the Ethics in
Animal Research Committee of the School of Dentistry
of Araraquara (UNESP, Brazil) (Process No. 15/2004)
in compliance with the applicable ethical guidelines
and regulations of the International Guiding Principles
for Biomedical Research Involving Animals (Geneva,
1985).
Animals
Sixty-six female Wistar rats (Rattus norvegicus al-
binus) aged approximately 60 days and weighing 180 to
220 g were used in this study. The animals were kept in
individual cages under climate-controlled conditions
(25°C; 55% humidity; 12 hours 30 minutes of light
alternating with 11 hours 30 minutes of darkness), fed
a standard laboratory diet, and given tap water.
Study design
The rats were anesthetized intramuscularly with a
combination of ketamine chloride (Ketamina Agener;
Agener União Ltda, São Paulo, SP, Brazil; 0.08 mL/
100 g body weight) and 2% xylazine (Rompum; Bayer
S.A. São Paulo, SP, Brazil; 0.04 mL/100 g body
weight). An incision approximately 20 mm long was
made on the medial side of the left tibia proximal
metaphysis. After careful dissection, the bone tissue
was exposed. Bicortical implant beds were prepared by
using a progressive sequence of the rotary drills cooled
with sterile saline solution. A microimplant (AS Tech-
nology, São José dos Campos, SP, Brazil) with a sand-
blasted and acid-etched surface (4.0 mm in length and
2.2 mm in diameter) was placed. Soft tissues were
sutured and postoperatively the animals received an
intramuscular antibiotic injection (Pentabiótico Pequeno
Porte; Fort Dodge, Campinas, SP, Brazil; 1 mL/kg body
weight). After a bone-healing period of 60 days, to
allow for osseointegration according to Cloki and War-
Giro et al. 163
shawsky,8 the animals were randomly divided into 5
groups: control group (CTL, n ⫽ 10), sham surgery
group (SHAM, n ⫽ 14), ovariectomy group (OVX, n ⫽
14), ovariectomy ⫹ estrogen replacement therapy
group (EST, n ⫽ 14), and ovariectomy ⫹ alendronate
group (ALE, n ⫽ 14). The CTL group was humanely
killed to confirm bone healing around the implants
radiographically. The SHAM group was submitted to
fictitious surgery and the OVX, EST, and ALE groups
were submitted to ovariectomy to evaluate the effect of
estrogen deficiency on bone already healed around den-
tal implants. The animals in the EST group received
daily subcutaneous injections of 17 ␤-estradiol (20
␮g/kg body weight) (Sigma Chemical Co., St. Louis,
MO), initiating 5 days postovariectomy. The animals in
the ALE group received subcutaneous injections of
alendronate (50 ␮g/kg body weight) in alternate days,
initiating 5 days postovariectomy. Ninety days after
ovariectomy (or sham surgery), the animals in SHAM,
OVX, EST, and ALE groups were euthanized with a
lethal intraperitoneal dose of 20% chloral hydrate (2
mL/kg body weight) (Fig. 1).
Densitometric evaluation by dual-energy x-ray
absorptiometry
To confirm the existence of systemic bone mass loss,
the femur and lumbar vertebrae (L2, L3, and L4) were
analyzed by dual-energy x-ray absorptiometry (DXA)
using the densitometer (QDR 2000 Hologic, Bedford,
MA) operating in the high-resolution mode and using
specific software for small animals supplied by the
equipment’s manufacturer. The technique was stan-
dardized for each type of bone. For the femur, mea-
surements of bone mineral density (BMD) were made
of global BMD and of 3 subregions: distal epiphysis
(R1), proximal epiphysis (R2), and diaphysis (R3). For
the lumbar vertebrae, global BMD and the bone min-
eral density in L2, L3, and L4 were measured (Fig. 2).
DXA accuracy for determination of bone mineral den-
sity was evaluated by measuring the coefficient of
variation expressed as a percentage of the mean.9,10 For
this reason, 5 consecutive measurements were made of

164 Giro et al.
Fig. 2. Regions evaluated in femoral densitometry (A) and
lumbar spine densitometry (B).
each anatomic area of the same specimen. The coeffi-
cient of variation of the densitometer was 0.6% for the
femur and 1.2% for the lumbar vertebrae, indicating
that the method was accurate.
Radiographic bone density—image acquisition
Digital radiographs were made using complementary
metal-oxide semiconductor (CMOS) equipment
(Schick Technologies Inc., Dialom Dental Products,
Long Island City, NY). The tibiae were fixed in a
holding device with the vertical long axis of the implant
positioned perpendicularly to the central x-ray beam
and parallel to the sensor at 40-cm focus-object dis-
tance. The x-ray unit was operated at 70 KVp, 10 mA,
and 0.3 s (Expectro 70x, Dabi Atlante, Ribeirão Preto,
SP, Brazil). A wooden block of 2 cm in thickness was
placed between the leg and the x-ray source to increase
secondary radiation.
Image resolution was 635 ppi (pixels per inch), the
size of the image was 900 ⫻ 641 dpi and pixel size was
40 ␮m. Images were stored in the TIFF (Tagged Image
File Format) without compression (8 bits with 600 dpi
resolution).
Imaging analysis
The images were analyzed using an image-analysis
software (Adobe Photoshop 6.0; Adobe Systems Incor-
porated, San Jose, CA) using a personal computer (Intel
Corp., Santa Clara, CA; Pentium M; 1.73 GHz proces-
sor, 512k, 1 DDR Gb) with Windows XP Home opera-
tional system (Microsoft, Inc., Redmond, WA) and flat
15.4-inch WXGA TruBite display (Toshiba America,
Inc., New York, NY).
Bone density was evaluated using gray-level analysis
(histogram) in an area of 5 ⫻ 5 pixels for the regions of
OOOOE
February 2008
Fig. 3. Regions of interest for analysis of radiographic bone
densitometry (1 and 2: superior cortical; 3 and 4: cancellous
bone; 5 and 6: inferior cortical).
interest (ROI), namely superior cortical, cancelous, and
inferior cortical of both sides of the implants (Fig. 3).
The bone density calculations were performed by first
obtaining the gray levels of ROI. The average of gray
level of the ROIs was divided by the gray level of the
implant to compensate minimal differences among ra-
diographs, since the density of the implant was equal in
all specimens.
Statistical analysis
The Kolmogorov-Smirnov test was used to verify
data distribution. Data from femoral and lumbar spine
densitometry were analyzed statistically by Kruskal-
Wallis and multiple comparisons. Data from radio-
graphic bone density were analyzed statistically by
analysis of variance (ANOVA) and Tukey’s test. Sig-
nificance level was set at 5%.
RESULTS
Bone densitometry
The results of femoral densitometry showed statisti-
cally significant differences (P ⬍ .05) among the
groups in all regions (Fig. 4). The lowest values were
observed in the OVX group while the highest values
were observed in the ALE group. Similar results were
found for lumbar spine bone densitometry. However,
no statistically significant difference (P ⬎ .05) was
found between CTL, SHAM, and ALE groups in some
of the evaluated regions (Fig. 5). The EST group did
not differ significantly (P ⬎ .05) from the CTL and
SHAM groups.
Radiographic analysis
Data from the radiographic analysis of the regions of
interest are given in Table I. The analysis of the radio-
OOOOE
Volume 105, Number 2 Giro et al. 165

therapy is a highly effective treatment to prevent ovari-

ectomy-induced bone loss. In spite of its numerically
higher values, the ALE group did not differ signifi-
cantly from the EST group (P ⬎ .05). The analysis of
the data relative to the cancellous bone region showed
that the OVX group presented radiographic bone den-
sity statistically lower than the other groups (P ⬍ .05),
whereas the ALE group presented the highest values
and differed significantly from the other groups (P ⬍
.05). The results of the EST group did not differ sig-
Fig. 4. Comparison between the groups for the bone density nificantly from those of the CTL and SHAM groups.
(g/cm2) of femur. *P ⱕ .05 for the OVX group in comparison
to the other groups. §P ⱕ .05 for the ALE group in compar-
ison to the other groups. DISCUSSION
Osteoporosis is an osteometabolic disorder charac-
terized by progressive bone resorption accompanied by
osteogenesis decrease.11 This study evaluated the influ-
ence of ovariectomy-induced estrogen deficiency and
its treatments on the bone tissue surrounding titanium
implants with established osseointegration. In animals,
osteoporosis may be experimentally induced by differ-
ent methods. Ovariectomy is the most widely used
method to obtain a postmenopausal osteoporosis ani-
mal model and for this reason it was selected for the
present study.12,13 Regarding the postovariectomy time
interval, a 90-day estrogen privation period was estab-
Fig. 5. Comparison between the groups for the bone density lished because the OVX-related bone alterations can be
(g/cm2) of lumbar vertebrae. *P ⱕ .05 for the OVX group in histologically observed as early as 30 days postovari-
comparison to the other groups. §P ⱕ .05 for the ALE group ectomy.14
in comparison to the other groups. Regarding the evaluated drug therapies, it is impor-
tant to emphasize that the estrogen replacement therapy
is the first choice and the most-used treatment approach
for prevention and management of cases of osteoporo-
Table I. Means and standard deviations of radio- sis. Alendronate was selected because it is a widely
graphic bone density values in CTL, SHAM, OVX, used drug in the treatment of osteoporosis and is con-
EST, and ALE groups in the evaluated areas* sidered as an alternative to estrogens, which, among
Superior bone Inferior bone other side effects, might be involved in the develop-
cortical Cancellous bone cortical
a
ment of endometrial cancer.15
CTL 0.48 ⫾ 0.02 0.34 ⫾ 0.03a 0.33 ⫾ 0.03a,b Studies16-20 have investigated the systemic condi-
SHAM 0.52 ⫾ 0.03a,b 0.34 ⫾ 0.01a 0.34 ⫾ 0.02a,b
OVX 0.49 ⫾ 0.05a 0.28 ⫾ 0.01b 0.32 ⫾ 0.02a
tions that might affect the bone tissue both structurally
EST 0.54 ⫾ 0.02b,c 0.37 ⫾ 0.02a 0.37 ⫾ 0.02b,c and functionally because the success of osseointegra-
ALE 0.57 ⫾ 0.05c 0.43 ⫾ 0.05c 0.4 ⫾ 0.03c tion depends, among other factors, on the healing ca-
CTL, control group; SHAM, sham surgery group; OVX, ovarectomy
pacity of the bone tissue around the implant. The re-
group; EST, ovariectomy ⫹ estrogen replacement therapy group; view of literature21-23 reveals that osteoporosis may be
ALE, ovariectomy ⫹ alendronate group. considered as a contraindication for placement of dental
*Different letters indicate groups with different characteristics. implants because this disorder affects the maxilla and
mandible as well as the axial and apendicular skeletons.
It is assumed that the compromised bone metabolism
would negatively affect the healing process in the bone
graphic bone density of the superior cortical and infe- tissue surrounding the implants.24
rior cortical showed that the ovariectomy did not cause In this study, DXA bone densitometric analysis per-
significant alterations in comparison to CTL and formed in 3 distinct femoral regions and in 3 distinct
SHAM groups. The EST group also presented radio- lumbar vertebrae revealed that OVX induced bone
graphic bone density values close to those of the CTL mass loss in all regions examined. These findings are
and SHAM groups, which demonstrates that estrogen consistent with those of a previous study,25 in which the

166 Giro et al.
induction of estrogen deficiency in ovariectomized rats
caused bone structural alterations with lower density in
long bones. Nevertheless, bone mass loss was not ob-
served either in the CTL group or in the other experimen-
tal groups. Estrogen- and alendronate-based treatments
proved to be effective in preventing postovariectomy bone
mass loss both in the femur and in the lumbar vertebrae.
These results are in accordance with those of Da Paz
et al.26 and Omi and Ezawa,27 who evaluated the effects
of estrogen in long bones and lumbar vertebrae of
ovariectomized rats and observed that hormone admin-
istration was able to inhibit bone mass loss, especially
in cancellous bone areas. Regarding the cortical bone,
the authors did not find any differences in bone mass
loss because this type of bone is not subjected to the
effects of estrogen privation. Alendronate produced a
significant increase in BMD in the evaluated areas,
especially in comparison to the OVX group. This is in
agreement with the results of previous studies,28,29
demonstrated that the alendronate increases the bone
mass because of the decrease in bone remodeling, with
consequent increase in the trabecular volume and the
number of bone trabeculae.26
Different methods have been used for evaluation of
the conditions of bone tissue around the implants. The
radiographic analysis is an important adjunctive tool to
clinical evaluation because it is a rapid, noninvasive,
low-cost method. The method used in this study for
radiographic analysis30,31 allows evaluating the relative
bone density around implants by analyzing the gray
levels in a specific area using image-analysis software.
It has been demonstrated that this method is able to
produce similar results to those of histological stud-
ies.30,32
The findings of radiographic bone density showed
that the effects of estrogen privation are greater in the
cancellous bone region than in the cortical bones. How-
ever, although the OVX group did not present a statis-
tically significant difference for the cortical regions in
comparison to the CTL and SHAM groups, it had the
lowest values. Regarding the cancellous bone region,
the OVX group presented the lowest values and was
statistically different from the other groups (P ⬍ .05).
This difference may be explained by the increase of the
medullar spaces, resulting from the decrease in the
number and thickness of the trabeculae with consequent
decrease in the bone mineral content in this region.33
The speed of bone remodeling should also be consid-
ered in the evaluated regions because the remodeling of
the cancellous bone is 10 times greater than that of the
cortical bone, which might explain the different re-
sponses observed for these 2 regions.34
The EST group did not differ significantly from the
CTL and SHAM groups in any of the evaluated areas.
OOOOE
February 2008
This is in agreement with the results of previous stud-
ies,6,35,36 which demonstrates that daily hormone ad-
ministration protects the bone tissue from the deleteri-
ous effects of estrogen privation.
The group treated with alendronate presented the
highest values and was statistically different from the
other groups for all evaluated areas; however, the effect
of this drug was more intense in the cancellous bone
region. The findings of the present study are consistent
with the systemic effects of alendronate reported by Da
Paz et al.26 and Andersson et al.28 They are also similar
to the findings of Duarte et al.20 and Narai and Naga-
hata,7 who demonstrated by histometrical and biome-
chanical analyses that animals treated with alendronate
presented greater resistance to implant removal, larger
bone/implant contact area, larger bone area between the
implant threads, and higher bone density in areas lateral
to implant surface. Although authors37-39 have reported
some cases that show association of the occurrence of
osteonecrosis of the jaw and therapy with bisphospho-
nates, it should be stressed that these involved use of
other types of bisphosphonates as well as with higher
doses as used for treatment of cancer metastasis or as
associated with an infectious process.
Within the limitations of this study, it may be con-
cluded that the ovariectomy, with consequent estrogen
privation, negatively affected radiographic bone den-
sity in the cancellous bone region around implants with
established osseointegration. Both systemic therapies
evaluated in this study were effective in preventing
bone mass loss and the administration of alendronate
resulted in higher bone density, especially in the can-
cellous bone region. Although alendronate yielded bet-
ter results, it should be taken into account that, in the
present study, the implants were inserted in the tibia.
However, the accumulation of alendronate in the jaw-
bones may be greater than that observed in the long
bones. In addition, the jawbones are more frequently
handled and are more susceptible to infection. There-
fore, further studies with loading of implants should be
considered before any suggestion that alendronate ther-
apy would be beneficial for implant survival in osteo-
porotic bone.
REFERENCES
1. van Steenberghe D, Quirynen M, Molly L, Jacobs R. Impact of
systemic diseases and medication on osseointegration. Periodon-
tol 2000 2003;33:163-71.
2. Consensus Development Conference on Osteoporosis. Am J
Med 1993;95A:5S-16S.
3. Bagi CM, Wilkie D, Georgelos K, Williams D, Bertolini D.
Morphological and structural characteristics of the proximal fe-
mur in human and rat. Bone 1997;21:261-7.
4. Friedlander AH. The physiology, medical management and oral
implications of menopause. J Am Dent Assoc 2002;133:73-81.
5. Tresguerres IF, Clemente C, Donado M, Gomez-Pellico L,
 OOOOE
Volume 105, Number 2
Blanco L, Alobera MA, et al. Local administration of growth
hormone enhances periimplant bone reaction in an osteoporotic
rabbit model. Clin Oral Implants Res 2002;13:631-6.
6. Duarte PM, Cesar-Neto JB, Gonçalves PF, Sallum EA, Nociti
FH Jr. Estrogen deficiency affects bone healing around titanium
implants: a histometric study in rats. Implant Dent 2003;12:340-6.
7. Narai S, Nagahata S. Effects of alendronate on the removal
torque of implants in rats with induced osteoporosis. Int J Oral
Maxillofac Implants 2003;18:218-23.
8. Clokie CM, Warshawsky H. Development of a rat tibia model for
morphological studies of the interface between bone and a tita-
nium implant. Compendium 1995;16:56-60.
9. Gala Paniagua J, Diaz-Curiel M, de la Piedra Gordo C, Castilla
Reparaz C, Torralbo Garcia M. Bone mass assessment in rats by
dual energy x-ray absortiometry. Br J Radiol 1998;71:754-8.
10. Grier SJ, Turner AS, Alvis MR. The use of dual-energy x-ray
absorptiometry in animals. Invest Radiol 1996;31:50-62.
11. Nasu M, Amano Y, Kurita A, Yosue T. Osseointegration in
implant-embedded mandible in rats fed calcium-deficient diet:
a radiological study. Oral Dis 1998;4:84-9.
12. Devlin H, Ferguson MWJ. The rate of incisor dentine calcifica-
tion and of mandibular growth in the molar region of the ovari-
ectomized rat. Arch Oral Biol 1990;35:29-32.
13. Kalu DN. The ovariectomized rat model of postmenopausal bone
loss. Bone Miner 1991;5:175-92.
14. Wronski TJ, Lowry PL, Walsh CC, Ignaszewski LA. Skeletal
alterations in ovariectomized rats. Calcif Tissue Int 1985;37:
324-8.
15. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooper-
berg C, Stefanick ML, et al. Risks and benefits of estrogen plus
progesterin in healthy postmenopausal women. 2002;288:
321-33.
16. Sakakura CE, Margonar R, Holzhausen M, Nociti FH Jr, Alba
RC Jr, Marcantonio E Jr. Influence of cyclosporin a therapy on
bone healing around titanium implants: a histometric and bio-
mechanic study in rabbits. J Periodontol 2003;74:976-81.
17. Margonar R, Sakakura CE, Holzhausen M, Pepato MT, Alba RC,
Marcantonio E. The influence of diabetes mellitus and insulin
therapy on biomechanical retention around dental implants: a
study in rabbits. Implant Dent 2003;12:333-9.
18. Lugero GG, De Falco Caparbo V, Guzzo ML, Konig B Jr,
Jorgetti V. Histomorphometric evaluation of titanium implants in
osteoporotic rabbits. Implant Dent 2000;9:303-9.
19. Cho P, Schneider GB, Krizan K, Keller JC. Examination of the
bone-implant interface in experimentally induced osteoporotic
bone. Implant Dent 2004;13:79-87.
20. Duarte PM, de Vasconcelos Gurgel BC, Sallum AW, Filho GR,
Sallum EA, Nociti FH Jr. Alendronate therapy may be effective
in the prevention of bone loss around titanium implants inserted
in estrogen-deficient rats. J. Periodontol 2005;107-14.
21. Horner K, Devlin H, Alsop CW, Hodgkinson IM, Adams JE.
Mandibular bone mineral density as a predictor of skeletal os-
teoporosis. Br J Radiol 1996;69:1019-25.
22. Jacobs R, Ghyselen J, Koninckx P, Van Steenberghe D. Long-
term bone mass evaluation of mandible and lumbar spine in a
group of women receiving hormone replacement therapy. Eur
J Oral Sci 1996;104:10-6.
23. von Wowern N, Klausen B, Kollerup G. Osteoporosis: a risk
factor in periodontal disease. J Periodontol 1994;65:1134-8.
24. Dao TT, Anderson JD, Zarb GA. Is osteoporosis a risk factor for
osseointegration of dental implants? Int J Oral Maxillofac Im-
plants 1993;8:137-44.
View publication stats
Giro et al. 167
25. Rico H, Gomez M, Revilla M, Gonzalez-Riola J, Seco C, Her-
nandez ER, et al. Effects of promethazine on bone mass and on
bone remodeling in ovariectomized rats: a morphometric, densi-
tometric, and histomorphometric experimental study. Calcif Tis-
sue Int 1999;65:272-5.
26. Da Paz LH, de Falco V, Teng NC, dos Reis LM, Pereira RM,
Jorgetti V. Effect of 17 beta-estradiol or alendronate on the bone
densitometry, bone histomorphometry and bone metabolism of
ovariectomized rats. Braz J Med Biol Res 2001;34:1015-22.
27. Omi N, Ezawa I. The effect of ovariectomy on bone metabolism
in rats. Bone 1995;17:163-8.
28. Andersson N, Surve VV, Lehto-Axtelius D, Ohlsson C, Hakan-
son R, Andersson K, et al. Drug-induced prevention of gastrec-
tomy and ovariectomy-induced osteopenia in the young female
rat. J Endocrinol 2002;175:695-703.
29. Andersson N, Surve VV, Lehto-Axtelius D, Andersson K, Ry-
berg B, Ohlsson C, et al. Pharmacological treatment of osteope-
nia induced by gastrectomy or ovariectomy in young female rats.
Acta Ortho Scand 2004;75:201-9.
30. Taba M Jr, Novaes AB Jr, Souza SL, Grisi MF, Palioto DB,
Pardini LC. Radiographic evaluation of dental implants with
different surface treatments: an experimental study in dogs. Im-
plant Dent 2003;12:252-8.
31. Sakakura CE, Giro G, Gonçalves D, Pereira RMR, Orrico SRP,
Marcantonio-Júnior E. Radiographic assessment of bone density
around osseointegrated titanium implants after ovariectomy in
rats. Clin Oral Impl Res 2006;17:134-8.
32. Novaes AB Jr, Souza SL, de Oliveira PT, Souza AM. Histomor-
phometric analysis of the bone-implant contact obtained with 4
different implant surface treatments placed side by side in the
dog mandible. Int J Oral Maxillofac Implants 2002;17:377-83.
33. Marcus R. Biochemical assessment of bone resorption and for-
mation. Bone 1996;18:15S-6S.
34. Väänänen HK. Mechanism of bone turnover. Ann Med
1993;25:353-9.
35. Wronski TJ, Dann LM, Qi H, Yen CF. Skeletal effects of
withdrawal of estrogen and diphosphonate treatment in ovariec-
tomized rats. Calcif Tissue Int 1993;53:210-6.
36. Sims NA, Morris HA, Moore RJ, Durbridge TC. Estradiol treat-
ment transiently increases trabecular bone volume in ovariecto-
mized rats. Bone 1996;19:455-61.
37. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-
induced exposed bone (osteonecrosis/osteopetrosis) of the jaws:
risk factors, recognition, prevention, and treatment. J Oral Max-
illofac Surg 2005;63:1567-75.
38. Farrugia MC, Summerlin DJ, Krowiak E, Huntley T, Freeman S,
Borrowdale R, et al. Osteonecrosis of the mandible or maxilla
associated with the use of new generation bisphosphonates. La-
ryngoscope 2006;116:115-20.
39. Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related os-
teonecrosis of the jaw: background and guidelines for diagnosis,
staging and management. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2006;102:433-41.
Reprint requests:
Gabriela Giro. DDS, MSc
Departamento de Diagnóstico e Cirurgia
Faculdade de Odontologia de Araraquara
UNESP, Rua Humaitá, 1680
14801-903, Araraquara, SP, Brazil
gabriela_giro@terra.com.br