Effect of Estrogen Deficiency on Implant Osseointegration in Dogs Nan Hua, PhD1/Yuanzhi Xu, PhD2/Xiaoshan Tang, DDS2/ Guangwei Shang, DDS2/Yun Shen, DDS2/Raorao Wang, PhD3 Purpose: This study investigated the effect of the absence of estrogen on the process of implant osseointegration in the jaws of beagle dogs. Materials and Methods: Of eight beagle dogs, four underwent bilateral ovariectomy (OVX), and the other four constituted a control group. Twelve weeks postsurgery, XiVE implants (Dentsply) were placed in the second premolar site in the mandible and in the canine site in the maxilla. Zero, 4, 8, 12, and 16 weeks after implant placement, implant stability quotients (ISQs) were measured by resonance frequency analysis (RFA). Results: The blood estrogen levels 12 weeks postsurgery were 5.8 ± 1.8 pg/mL in the OVX group and 37.0 ± 2.9 pg/mL in the control group, which represents a significant decrease (P < .01). The ISQ of maxillary implants in the OVX group 12 weeks after implant placement was 64.5 ± 1.7, and in the control group it was 74.3 ± 1.5; the ISQ was significantly reduced in the OVX group (.01 < P < .05). Conclusion: The results of this study indicate that the absence of estrogen induced by OVX in beagle dogs could reduce osseointegration around maxillary implants but has little influence in the mandible. Int J Oral Maxillofac Implants 2014;29:1204–1207. doi: 10.11607/jomi.3557 Key words: beagle dog, dental implants, estrogen deficiency, osseointegration, ovariectomy
I
n the past decade, endosseous dental implants have become a popular first choice for the rehabilitation of the edentulous patient. Although long-term implant survival rates exceed 90%,1,2 it is still important to consider the effects of several systemic factors, such as smoking and osteoporosis, in treatment planning, because these factors can predispose patients to higher rates of implant failure.3,4 Osteoporosis is a metabolic condition commonly associated with bone deficiency and characterized by decreased bone mass and strength, leading to increased fracture risk after minimal trauma. More than 70 million people worldwide are affected by osteoporosis.5 Once a tooth is lost, the impact of osteoporosis could be a factor in the success of dental implant
therapy.6,7 Despite extensive clinical and animal research, the mechanisms by which osteoporosis leads to implant failure remain incompletely understood. Estrogen deficiency may contribute to osteoporosis as a risk factor in implant failure, and previous studies have indicated that an estrogen-deficient state could affect bone healing and bone density around titanium implants placed in rats, especially in cancellous bone.8–10 Few studies have examined the effects of estrogen on implant osseointegration in the beagle dog, the classic animal model in dental implant research. The aim of this present work was to describe the effects of ovariectomy (OVX)–induced estrogen depletion on the process of osseointegration of screwtype titanium implants in the maxillae and mandibles of beagle dogs.
1Lecturer,
Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China; Department of Stomatology, Shanghai Yangsi Hospital, Shanghai, China. 2Lecturer, Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China. 3 Professor, Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China. Correspondence to: Dr Raorao Wang, Department of Stomatology, the Tenth People’s Hospital, Tongji University, 299 Yanchang Road, Shanghai 200072, PR China. Fax: 86-21-66301725. Email: [email protected] ©2014 by Quintessence Publishing Co Inc.
MATERIALS AND METHODS Animal Use and Surgical Techniques
All experiments were approved by the Ethics Committee of Experimentation at the Shanghai Tongji University, China. Eight female beagle dogs (obtained from the Shanghai Laboratory Animal Center [SLAC], China), 12 to 14 months old, with an average body weight of 12.0 ± 1.0 kg, were used. The second mandibular premolars and maxillary canines of all animals were extracted under general anesthesia with intramuscular injections of 2% thiazine and 10% ketamine. Twelve weeks after tooth extraction, after alveolar wound
1204 Volume 29, Number 5, 2014 © 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Hua et al
Table 1 Results of 17-β-Estradiol Content in Blood Samples (pg/mL) Period (wk)
OVX No. 1
No. 2
Control No. 3
No. 4
Mean ± SD
No. 1
No. 2
No. 3
No. 4
Mean ± SD
0
22
24
31
29
26.5 ± 4.2
27
29
31
25
28.0 ± 2.6
4
13
12
15
13
13.3 ± 1.3
25
27
29
27
27.0 ± 1.6
8
4
7
9
11
7.8 ± 2.4
33
34
39
37
35.8 ± 3.8
12
7
4
5
7
5.8 ± 1.8
35
40
39
34
37.0 ± 2.9
16
4
6
5
8
5.8 ± 1.5
42
39
44
36
40.3 ± 3.5
healing was completed,11 four dogs were randomly selected to undergo bilateral OVX under general anesthesia as described elsewhere,12 while the other four dogs underwent sham operations with the same surgical process as OVX, except that the ovary was not removed. The animals received food and water ad libitum and were weighed weekly.
calibration parameters of the transducer.14,15 A high ISQ value indicates high stability; a low ISQ value indicates low stability.
Testing for Estrogen Levels
The changes in 17-β-estradiol content in the blood samples of beagle dogs over a period of 16 weeks are presented in Table 1. A t test showed significant differences in estrogen levels between the OVX and control groups at 4 weeks postsurgery (P < .01).
At 2, 4, 6, 8, 10, and 12 weeks after OVX or sham operations, the dogs were anesthetized, and samples of blood (2 mL) were obtained by venipuncture. The serum concentrations of 17-β-estradiol were measured by radioimmunoassay with a commercially available radioimmunoassay kit (Boehringer Mannheim) and a gamma scintillation counter (Institute of Applied Physics, Chinese Academy of Sciences).
Implant Placement Procedure
Twelve weeks after the OVX operations, the eight dogs underwent implant surgery under general anesthesia. A crestal incision was made in the extraction area (second mandibular premolars and maxillary canines), together with a short releasing incision at sites proximal and distal to the flaps. After a drilling sequence, titanium XiVE implants (Dentsply) with 8-mm length and 3.4-mm diameter were placed, and computed tomography (CT) was used to examine the results of the available bone.
Resonance Frequency Analysis
Resonance frequency analysis (RFA) was performed according to Garg,13 with an Osstell Mentor apparatus (Osstell), on the day of implant placement and 4, 8, 12, and 16 weeks after implant placement. The Osstell Mentor has a liquid crystal display (LCD) screen and operates with a rechargeable power supply. A transducer is attached to the implant to enable the Osstell Mentor to measure implant stability. RFA values as measured by the Osstell Mentor are presented in a quantitative unit known as the implant stability quotient (ISQ). The ISQ varies from 0 to 100, and these values are derived from the stiffness (N/μm) of the transducer/implant bone unit and the
RESULTS Estrogen Level Testing
Implants
None of the dogs that underwent implant surgery in this study presented early postoperative complications such as local infection, and healing was uneventful. Radiography (Fig 1) indicated no significant space or inflammation between the implant and the bone.
Resonance Frequency Analysis
The mean implant ISQs in OVX and control dogs over a period of 16 weeks are presented in Table 2 and Figs 2 and 3. No statistically significant differences were found between OVX and control groups in the maxilla or mandible at the time of implant placement (P > .05). Differences were observed between test and control groups 4, 8, 12, and 16 weeks after implant placement in the maxilla (.01 < P < .05), but there were no statistically significant differences at any periods after placement in the mandible (P > .05).
DISCUSSION Recently, the reactions of bone tissues following the placement of implants under estrogen-deficient conditions have been studied in experimental rats.16,17 Generally, estrogen deficiency seems to have a negative influence on bone quality around titanium implants. The ovariectomized animal is a very useful model for postmenopausal osteoporosis studies in humans, and most published studies have used rats as the animal The International Journal of Oral & Maxillofacial Implants 1205
© 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Hua et al
a
b
Fig 1 (a) Mandibular and (b) maxillary radiographs of implants 16 weeks after placement.
Table 2 Means and Standard Deviations of ISQs in OVX and Control Dogs OVX
Period (wk)
Maxilla
Control
Mandible
Maxilla
Mandible
0 (baseline) 61.3 ± 3.0 79.8 ± 3.6 60.5 ± 4.0 80.8 ± 3.0 4
48.8 ± 3.9 76.3 ± 2.5 53.8 ± 2.2 74.0 ± 3.7
8
55.8 ± 1.7 81.0 ± 2.2 73.3 ± 1.8 84.3 ± 2.6
12
64.5 ± 1.7 83.3 ± 2.5 74.3 ± 1.5 83.8 ± 2.2
16
66.0 ± 1.2 82.8 ± 2.9 75.5 ± 1.3 84.5 ± 3.1 100
OVX
Control
12
16
80
ISQ
60 40 20 0
0
4
8 Period (wk)
Fig 2 Means of ISQs in the maxillae of OVX and control dogs. 100
OVX
Control
4
5
80
ISQ
60 40 20 0
1
2
3 Period (wk)
Fig 3 Means of ISQs in the mandibles of OVX and control dogs.
model.18 It is difficult to place implants in the alveolar area in rats because of the small body size, so in the present study, the beagle dog, the classic animal model in dental implant research, was used to investigate the impact of estrogen-deficient conditions on osseointegration of implants placed in jaws. The effectiveness of OVX was directly confirmed by the estrogen level test, the results of which indicated that OVX could induce ovarian hormone deficiency in beagle dogs. Extraction of the second mandibular premolar and maxillary canine was chosen in this study because there was sufficient space for the placement of screw-type implants, and the edentulous space had little influence on occlusion. RFA is determined by the stiffness of bone in relation to the most coronal part of the implant, so resonance frequency measurement has been used to evaluate implant stability during healing in bone.19 In classic theory, higher ISQ and insertion torque during the placement of implants indicate better implant-bone integration and stability,20 but recent studies have indicated that low insertion torque can yield favorable survival rates and optimal maintenance of marginal bone levels.21 The ISQ results of the OVX and control groups measured in this study indicated that estrogen deficiency induced by OVX could delay the process of osseointegration and decrease maxillary implant stability, but there was no significant influence in the mandible. Estrogen deficiency increases bone turnover and leads to an imbalance between resorption and bone formation.22 Bone loss due to ovarian hormone deficiency has been linked to hypercalcemic suppression of the parathyroid, which leads to a decrease in 1,25-dihydroxyvitamin D synthesis and gastrointestinal absorption of calcium. Furthermore, various cytokines, including interleukins 1, 6, and 11, tumor necrosis factor α (TNF-α), macrophage colony-stimulating factor (M-CSF), could play fundamental roles in bone resorption, facilitating
1206 Volume 29, Number 5, 2014 © 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Hua et al
the recruitment and maturation of osteoclast precursors.23 The structural modifications in new bone related to estrogen deficiency affect mainly cancellous bone.3 Because the percentage of cancellous bone in the maxilla is much higher than that in the mandible, the estrogen-deficient state has more influence on bone formation in the maxilla than in the mandible. That is why the results of ISQ measurement in this study indicated that an estrogen-deficient state could affect bone healing and osseointegration around titanium implants placed in the maxillae of beagle dogs, but this state had no effect in the mandible. The results of this present study are in agreement with those of previous studies regarding the influence of estrogendeficient conditions on bone healing around implants in cortical and cancellous bone regions in rats.24,25 Although there was no significant difference between the OVX and control groups in terms of the ISQ of the mandible, over the long term, the poor anchoring quality in cancellous bone in the mandible can also decrease the load-bearing capacity of the implants. Therefore, short implants in the mandible with long single-tooth crowns or subjected to bruxism may still show an increased failure rate in patients with osteoporosis. Further research is necessary.
CONCLUSION Within the limits of this animal study, the results suggested that the absence of estrogen induced by OVX in beagle dogs could delay the process of osseointegration around implants and reduce implant stability in the maxilla, with little influence in the mandible.
ACKNOWLEDGMENTS This work was supported by grants from the Science and Technology Commission of Shanghai Municipality (No. 10ZR1423400) and from the Shanghai Health Bureau (20114y056). The authors reported no conflicts of interest related to this study.
REFERENCES 1. Sherif S, Susarla SM, Hwang JW, Weber HP, Wright RF. Clinician- and patient-reported long-term evaluation of screw- and cementretained implant restorations: A 5-year prospective study. Clin Oral Investig 2011;15:993–999. 2. Blanes RJ, Bernard JP, Blanes ZM, Beslser UC. A 10-year prospective study of ITI dental implants placed in the posterior region. I: Clinical and radiographic results. Clin Oral Implants Res 2007;18:699–706. 3. Moy PK, Medina D, Shetty V, Aqhaloo TL. Dental implant failure rates and associated risk factors. Int J Oral Maxillofac Implants 2005;20:569–577. 4. Winkler S. Extraordinary implant failure. J Oral Implantol 2010;36:391–400.
5. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:340–357. 6. Reddy M. Osteoporosis and periodontitis: Discussion, conclusion, and recommendations. Ann Periodontol 2001;6:214–217. 7. Alsaadi G, Quirynen M, Komárek A, Steenberghe D. Impact of local and systemic factors on the incidence of oral implant failures, up to abutment connection. J Clin Periodontol 2007;34:610–617. 8. Duarte PM, César Neto JB, Gonçalves PF, Sallum EA, Humberto Nociti JF. Estrogen deficiency affects bone healing around titanium implants: A histometric study in rats. Implant Dent 2003;12:340–346. 9. Motohashi M, Shirota T, Tokugawa Y, Ohno K, Michi K, Yamaguchi A. Bone reactions around hydroxyapatite-coated implants in ovariectomized rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:145–152. 10. Giro G, Coelho PG, Sales-Pessoa R, et al. Influence of estrogen deficiency on bone around osseointegrated dental implants: An experimental study in the rat jaw model. J Oral Maxillofac Surg 2011;69:1911–1918. 11. Kunz C, Adolphs N, Büscher P, Hammer B, Rahn B. Mineralization and mechanical properties of the canine mandible distraction wound following acute molding. Int J Oral Maxillofac Surg 2006;35:822–827. 12. Lee WM, Kooistra HS, Mol JA, Dieleman SJ, Schaefers-Okkens AC. Ovariectomy during the luteal phase influences secretion of prolactin, growth hormone, and insulin-like growth factor-I in the bitch. Theriogenology 2006;15;66:484–490. 13. Garg AK. Osstell Mentor: Measuring dental implant stability at placement, before loading, and after loading. Dent Implantol Update 2007;18:49–53. 14. Ozcan Y, Ozcan M, Varol A, et al. Resonance frequency analysis assessment of implant stability in labial onlay grafted posterior mandibles: A pilot clinical study. Int J Oral Maxillofac Implants 2007;22:235–242. 15. Ersanli S, Karabuda C, Beck F, Leblebicioglu B. Resonance frequency analysis of one-stage dental implant stability during the osseointegration period. J Periodontol 2005;76:1066–1071. 16. Yamazaki M, Shirota T, Tokugawa Y, et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:411–418. 17. Pan J, Shirota T, Ohno K, Michi K. Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats. J Oral Maxillofac Surg 2000;58:877–882. 18. Namkung-Matthai H, Appleyard R, Jansen J, et al. Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone 2001;28:80–86. 19. Boronat López A, Balaguer Martínez J, Carrillo García C, Peñarrocha Diago M. Resonance frequency analysis of dental implant stability during the healing period. Med Oral Patol Oral Cir Bucal 2008;13:E244–E247. 20. Scarano A, Carinci F, Quaranta A, Iezzi G, Piattelli M, Piattelli A. Correlation between implant stability quotient (ISQ) with clinical and histological aspects of dental implants removed for mobility. Int J Immunopathol Pharmacol 2007;20(1 suppl 1):33–36. 21. Norton MR. The influence of insertion torque on the survival of immediately placed and restored single-tooth implants. Int J Oral Maxillofac Implants 2011;26:1333–1343. 22. Bauss F, Wagner M, Hothorn LH. Total administered dose of ibandronate determines its effects on bone mass and architecture in ovariectomized aged rats. J Rheumatol 2002;29:990–998. 23. Cenci S, Toraldo G, Weitzmann MN, et al. Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci USA 2003;100:10405–10410. 24. Nociti FH Jr, Sallum AW, Sallum EA, Duarte PM. Effect of estrogen replacement and calcitonin therapies on bone around titanium implants placed in ovariectomized rats: A histometric study. Int J Oral Maxillofac Implants 2002;17:786–792. 25. Viera-Negrón YE, Ruan WH, Winger JN, Hou X, Sharawy MM, Borke JL. Effect of ovariectomy and alendronate on implant osseointegration in rat maxillary bone. J Oral Implantol 2008;34:76–82.
The International Journal of Oral & Maxillofacial Implants 1207 © 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
I
n the past decade, endosseous dental implants have become a popular first choice for the rehabilitation of the edentulous patient. Although long-term implant survival rates exceed 90%,1,2 it is still important to consider the effects of several systemic factors, such as smoking and osteoporosis, in treatment planning, because these factors can predispose patients to higher rates of implant failure.3,4 Osteoporosis is a metabolic condition commonly associated with bone deficiency and characterized by decreased bone mass and strength, leading to increased fracture risk after minimal trauma. More than 70 million people worldwide are affected by osteoporosis.5 Once a tooth is lost, the impact of osteoporosis could be a factor in the success of dental implant
therapy.6,7 Despite extensive clinical and animal research, the mechanisms by which osteoporosis leads to implant failure remain incompletely understood. Estrogen deficiency may contribute to osteoporosis as a risk factor in implant failure, and previous studies have indicated that an estrogen-deficient state could affect bone healing and bone density around titanium implants placed in rats, especially in cancellous bone.8–10 Few studies have examined the effects of estrogen on implant osseointegration in the beagle dog, the classic animal model in dental implant research. The aim of this present work was to describe the effects of ovariectomy (OVX)–induced estrogen depletion on the process of osseointegration of screwtype titanium implants in the maxillae and mandibles of beagle dogs.
1Lecturer,
Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China; Department of Stomatology, Shanghai Yangsi Hospital, Shanghai, China. 2Lecturer, Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China. 3 Professor, Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China. Correspondence to: Dr Raorao Wang, Department of Stomatology, the Tenth People’s Hospital, Tongji University, 299 Yanchang Road, Shanghai 200072, PR China. Fax: 86-21-66301725. Email: [email protected] ©2014 by Quintessence Publishing Co Inc.
MATERIALS AND METHODS Animal Use and Surgical Techniques
All experiments were approved by the Ethics Committee of Experimentation at the Shanghai Tongji University, China. Eight female beagle dogs (obtained from the Shanghai Laboratory Animal Center [SLAC], China), 12 to 14 months old, with an average body weight of 12.0 ± 1.0 kg, were used. The second mandibular premolars and maxillary canines of all animals were extracted under general anesthesia with intramuscular injections of 2% thiazine and 10% ketamine. Twelve weeks after tooth extraction, after alveolar wound
1204 Volume 29, Number 5, 2014 © 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Hua et al
Table 1 Results of 17-β-Estradiol Content in Blood Samples (pg/mL) Period (wk)
OVX No. 1
No. 2
Control No. 3
No. 4
Mean ± SD
No. 1
No. 2
No. 3
No. 4
Mean ± SD
0
22
24
31
29
26.5 ± 4.2
27
29
31
25
28.0 ± 2.6
4
13
12
15
13
13.3 ± 1.3
25
27
29
27
27.0 ± 1.6
8
4
7
9
11
7.8 ± 2.4
33
34
39
37
35.8 ± 3.8
12
7
4
5
7
5.8 ± 1.8
35
40
39
34
37.0 ± 2.9
16
4
6
5
8
5.8 ± 1.5
42
39
44
36
40.3 ± 3.5
healing was completed,11 four dogs were randomly selected to undergo bilateral OVX under general anesthesia as described elsewhere,12 while the other four dogs underwent sham operations with the same surgical process as OVX, except that the ovary was not removed. The animals received food and water ad libitum and were weighed weekly.
calibration parameters of the transducer.14,15 A high ISQ value indicates high stability; a low ISQ value indicates low stability.
Testing for Estrogen Levels
The changes in 17-β-estradiol content in the blood samples of beagle dogs over a period of 16 weeks are presented in Table 1. A t test showed significant differences in estrogen levels between the OVX and control groups at 4 weeks postsurgery (P < .01).
At 2, 4, 6, 8, 10, and 12 weeks after OVX or sham operations, the dogs were anesthetized, and samples of blood (2 mL) were obtained by venipuncture. The serum concentrations of 17-β-estradiol were measured by radioimmunoassay with a commercially available radioimmunoassay kit (Boehringer Mannheim) and a gamma scintillation counter (Institute of Applied Physics, Chinese Academy of Sciences).
Implant Placement Procedure
Twelve weeks after the OVX operations, the eight dogs underwent implant surgery under general anesthesia. A crestal incision was made in the extraction area (second mandibular premolars and maxillary canines), together with a short releasing incision at sites proximal and distal to the flaps. After a drilling sequence, titanium XiVE implants (Dentsply) with 8-mm length and 3.4-mm diameter were placed, and computed tomography (CT) was used to examine the results of the available bone.
Resonance Frequency Analysis
Resonance frequency analysis (RFA) was performed according to Garg,13 with an Osstell Mentor apparatus (Osstell), on the day of implant placement and 4, 8, 12, and 16 weeks after implant placement. The Osstell Mentor has a liquid crystal display (LCD) screen and operates with a rechargeable power supply. A transducer is attached to the implant to enable the Osstell Mentor to measure implant stability. RFA values as measured by the Osstell Mentor are presented in a quantitative unit known as the implant stability quotient (ISQ). The ISQ varies from 0 to 100, and these values are derived from the stiffness (N/μm) of the transducer/implant bone unit and the
RESULTS Estrogen Level Testing
Implants
None of the dogs that underwent implant surgery in this study presented early postoperative complications such as local infection, and healing was uneventful. Radiography (Fig 1) indicated no significant space or inflammation between the implant and the bone.
Resonance Frequency Analysis
The mean implant ISQs in OVX and control dogs over a period of 16 weeks are presented in Table 2 and Figs 2 and 3. No statistically significant differences were found between OVX and control groups in the maxilla or mandible at the time of implant placement (P > .05). Differences were observed between test and control groups 4, 8, 12, and 16 weeks after implant placement in the maxilla (.01 < P < .05), but there were no statistically significant differences at any periods after placement in the mandible (P > .05).
DISCUSSION Recently, the reactions of bone tissues following the placement of implants under estrogen-deficient conditions have been studied in experimental rats.16,17 Generally, estrogen deficiency seems to have a negative influence on bone quality around titanium implants. The ovariectomized animal is a very useful model for postmenopausal osteoporosis studies in humans, and most published studies have used rats as the animal The International Journal of Oral & Maxillofacial Implants 1205
© 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Hua et al
a
b
Fig 1 (a) Mandibular and (b) maxillary radiographs of implants 16 weeks after placement.
Table 2 Means and Standard Deviations of ISQs in OVX and Control Dogs OVX
Period (wk)
Maxilla
Control
Mandible
Maxilla
Mandible
0 (baseline) 61.3 ± 3.0 79.8 ± 3.6 60.5 ± 4.0 80.8 ± 3.0 4
48.8 ± 3.9 76.3 ± 2.5 53.8 ± 2.2 74.0 ± 3.7
8
55.8 ± 1.7 81.0 ± 2.2 73.3 ± 1.8 84.3 ± 2.6
12
64.5 ± 1.7 83.3 ± 2.5 74.3 ± 1.5 83.8 ± 2.2
16
66.0 ± 1.2 82.8 ± 2.9 75.5 ± 1.3 84.5 ± 3.1 100
OVX
Control
12
16
80
ISQ
60 40 20 0
0
4
8 Period (wk)
Fig 2 Means of ISQs in the maxillae of OVX and control dogs. 100
OVX
Control
4
5
80
ISQ
60 40 20 0
1
2
3 Period (wk)
Fig 3 Means of ISQs in the mandibles of OVX and control dogs.
model.18 It is difficult to place implants in the alveolar area in rats because of the small body size, so in the present study, the beagle dog, the classic animal model in dental implant research, was used to investigate the impact of estrogen-deficient conditions on osseointegration of implants placed in jaws. The effectiveness of OVX was directly confirmed by the estrogen level test, the results of which indicated that OVX could induce ovarian hormone deficiency in beagle dogs. Extraction of the second mandibular premolar and maxillary canine was chosen in this study because there was sufficient space for the placement of screw-type implants, and the edentulous space had little influence on occlusion. RFA is determined by the stiffness of bone in relation to the most coronal part of the implant, so resonance frequency measurement has been used to evaluate implant stability during healing in bone.19 In classic theory, higher ISQ and insertion torque during the placement of implants indicate better implant-bone integration and stability,20 but recent studies have indicated that low insertion torque can yield favorable survival rates and optimal maintenance of marginal bone levels.21 The ISQ results of the OVX and control groups measured in this study indicated that estrogen deficiency induced by OVX could delay the process of osseointegration and decrease maxillary implant stability, but there was no significant influence in the mandible. Estrogen deficiency increases bone turnover and leads to an imbalance between resorption and bone formation.22 Bone loss due to ovarian hormone deficiency has been linked to hypercalcemic suppression of the parathyroid, which leads to a decrease in 1,25-dihydroxyvitamin D synthesis and gastrointestinal absorption of calcium. Furthermore, various cytokines, including interleukins 1, 6, and 11, tumor necrosis factor α (TNF-α), macrophage colony-stimulating factor (M-CSF), could play fundamental roles in bone resorption, facilitating
1206 Volume 29, Number 5, 2014 © 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Hua et al
the recruitment and maturation of osteoclast precursors.23 The structural modifications in new bone related to estrogen deficiency affect mainly cancellous bone.3 Because the percentage of cancellous bone in the maxilla is much higher than that in the mandible, the estrogen-deficient state has more influence on bone formation in the maxilla than in the mandible. That is why the results of ISQ measurement in this study indicated that an estrogen-deficient state could affect bone healing and osseointegration around titanium implants placed in the maxillae of beagle dogs, but this state had no effect in the mandible. The results of this present study are in agreement with those of previous studies regarding the influence of estrogendeficient conditions on bone healing around implants in cortical and cancellous bone regions in rats.24,25 Although there was no significant difference between the OVX and control groups in terms of the ISQ of the mandible, over the long term, the poor anchoring quality in cancellous bone in the mandible can also decrease the load-bearing capacity of the implants. Therefore, short implants in the mandible with long single-tooth crowns or subjected to bruxism may still show an increased failure rate in patients with osteoporosis. Further research is necessary.
CONCLUSION Within the limits of this animal study, the results suggested that the absence of estrogen induced by OVX in beagle dogs could delay the process of osseointegration around implants and reduce implant stability in the maxilla, with little influence in the mandible.
ACKNOWLEDGMENTS This work was supported by grants from the Science and Technology Commission of Shanghai Municipality (No. 10ZR1423400) and from the Shanghai Health Bureau (20114y056). The authors reported no conflicts of interest related to this study.
REFERENCES 1. Sherif S, Susarla SM, Hwang JW, Weber HP, Wright RF. Clinician- and patient-reported long-term evaluation of screw- and cementretained implant restorations: A 5-year prospective study. Clin Oral Investig 2011;15:993–999. 2. Blanes RJ, Bernard JP, Blanes ZM, Beslser UC. A 10-year prospective study of ITI dental implants placed in the posterior region. I: Clinical and radiographic results. Clin Oral Implants Res 2007;18:699–706. 3. Moy PK, Medina D, Shetty V, Aqhaloo TL. Dental implant failure rates and associated risk factors. Int J Oral Maxillofac Implants 2005;20:569–577. 4. Winkler S. Extraordinary implant failure. J Oral Implantol 2010;36:391–400.
5. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:340–357. 6. Reddy M. Osteoporosis and periodontitis: Discussion, conclusion, and recommendations. Ann Periodontol 2001;6:214–217. 7. Alsaadi G, Quirynen M, Komárek A, Steenberghe D. Impact of local and systemic factors on the incidence of oral implant failures, up to abutment connection. J Clin Periodontol 2007;34:610–617. 8. Duarte PM, César Neto JB, Gonçalves PF, Sallum EA, Humberto Nociti JF. Estrogen deficiency affects bone healing around titanium implants: A histometric study in rats. Implant Dent 2003;12:340–346. 9. Motohashi M, Shirota T, Tokugawa Y, Ohno K, Michi K, Yamaguchi A. Bone reactions around hydroxyapatite-coated implants in ovariectomized rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:145–152. 10. Giro G, Coelho PG, Sales-Pessoa R, et al. Influence of estrogen deficiency on bone around osseointegrated dental implants: An experimental study in the rat jaw model. J Oral Maxillofac Surg 2011;69:1911–1918. 11. Kunz C, Adolphs N, Büscher P, Hammer B, Rahn B. Mineralization and mechanical properties of the canine mandible distraction wound following acute molding. Int J Oral Maxillofac Surg 2006;35:822–827. 12. Lee WM, Kooistra HS, Mol JA, Dieleman SJ, Schaefers-Okkens AC. Ovariectomy during the luteal phase influences secretion of prolactin, growth hormone, and insulin-like growth factor-I in the bitch. Theriogenology 2006;15;66:484–490. 13. Garg AK. Osstell Mentor: Measuring dental implant stability at placement, before loading, and after loading. Dent Implantol Update 2007;18:49–53. 14. Ozcan Y, Ozcan M, Varol A, et al. Resonance frequency analysis assessment of implant stability in labial onlay grafted posterior mandibles: A pilot clinical study. Int J Oral Maxillofac Implants 2007;22:235–242. 15. Ersanli S, Karabuda C, Beck F, Leblebicioglu B. Resonance frequency analysis of one-stage dental implant stability during the osseointegration period. J Periodontol 2005;76:1066–1071. 16. Yamazaki M, Shirota T, Tokugawa Y, et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:411–418. 17. Pan J, Shirota T, Ohno K, Michi K. Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats. J Oral Maxillofac Surg 2000;58:877–882. 18. Namkung-Matthai H, Appleyard R, Jansen J, et al. Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone 2001;28:80–86. 19. Boronat López A, Balaguer Martínez J, Carrillo García C, Peñarrocha Diago M. Resonance frequency analysis of dental implant stability during the healing period. Med Oral Patol Oral Cir Bucal 2008;13:E244–E247. 20. Scarano A, Carinci F, Quaranta A, Iezzi G, Piattelli M, Piattelli A. Correlation between implant stability quotient (ISQ) with clinical and histological aspects of dental implants removed for mobility. Int J Immunopathol Pharmacol 2007;20(1 suppl 1):33–36. 21. Norton MR. The influence of insertion torque on the survival of immediately placed and restored single-tooth implants. Int J Oral Maxillofac Implants 2011;26:1333–1343. 22. Bauss F, Wagner M, Hothorn LH. Total administered dose of ibandronate determines its effects on bone mass and architecture in ovariectomized aged rats. J Rheumatol 2002;29:990–998. 23. Cenci S, Toraldo G, Weitzmann MN, et al. Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci USA 2003;100:10405–10410. 24. Nociti FH Jr, Sallum AW, Sallum EA, Duarte PM. Effect of estrogen replacement and calcitonin therapies on bone around titanium implants placed in ovariectomized rats: A histometric study. Int J Oral Maxillofac Implants 2002;17:786–792. 25. Viera-Negrón YE, Ruan WH, Winger JN, Hou X, Sharawy MM, Borke JL. Effect of ovariectomy and alendronate on implant osseointegration in rat maxillary bone. J Oral Implantol 2008;34:76–82.
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