Bone Formation Around Titanium Implants in the Rat Tibia: Role of Insulin

/Home/Dental Implants (Prosthodontics)/Dental Implants (Prosthodontics)Articles & Reports/Group 6

Bone Formation Around Titanium Implants in the Rat Tibia: Role of Insulin
September 2003
Siqueira, Jos?© T. DDS, PhD*; Cavalher-Machado, Simone C. MSc**; Arana-Chavez, Victor E. DDS, PhD***; Sannomiya, Paulina PhD**
*Supervisor of Orofacial Pain Team, Division of Dentistry, University of S?Ło Paulo Medical School, S?Ło Paulo, Brazil.
**Associate Professor, Research Division, Institute of Heart (Incor), University of S?Ło Paulo Medical School, S?Ło Paulo, Brazil.
***Associate Professor, Laboratory of Mineralized Tissue Biology, Department of Histology and Embryology, Institute of Biomedical Sciences, University of S?Ło Paulo, S?Ło Paulo, Brazil.
Reprint requests and correspondence to: Paulina Sannomiya, PhD, Research Division, Institute of Heart (Incor), University of S?Ło Paulo Medical School, Av. Dr. En?©as de Carvalho Aguiar, 44, 05403-900 S?Ło Paulo, SP, Brazil
Implant Dentistry: Volume 12(3) September 2003 pp 242-251
Please visit the web site to view the article in its entirety.
Abstract
Background and Purpose: Clinical and experimental studies show, with few exceptions, that type 1 diabetes mellitus is associated with a delay in bone repair around endosseous implants. The effect of insulin in bone repair/remodeling is not completely understood. The aim of this study was to investigate the course of histological and ultrastructural changes of the osseointegration process under the influence of insulin.
Materials and Methods: Titanium implants were inserted into the tibiae of male Wistar rats. Animals were divided into three groups: 1) rats with alloxan-induced diabetes; 2) diabetic rats treated with isophane insulin (2 IU/day); and 3) matching controls. Histological and histomorphometric analysis of bone-implant sections were performed 10 and 21 days after implant placement.
Results: Relative to control values, rats with alloxan-induced diabetes exhibited a 50% reduction in the area of formed bone (P < 0.001) and in the surface of contact between bone and implant (P < 0.01) 21 days after implant placement. There were no significant differences between groups 10 days after surgery. Values returned to normal levels in diabetic rats after insulin treatment. Presence of chondrocytelike cells surrounded by a cartilaginouslike matrix in diabetic rats suggests a delay in the process of bone repair. Ultrastructural characteristics of bone-implant interface in diabetic rats treated with insulin resembled those observed in controls.
Conclusion: The data presented suggest that bone repair around endosseous implants is regulated, at least in part, by insulin. The results imply that the control of the metabolic status of the diabetic patient is essential for a successful osseointegration.
References
1. Branemark PI. Introduction to osseointegration. In: Branemark PI, Zarb GA, Albrektsson T, eds. Osseointegration in Clinic Dentistry. Chicago, IL: Quintessence Books; 1985: 11-76.
2. Branemark PI, Lausma J, Ericson L, et al. Anatomy of osseointegration and the transfer of load. In: Fonseca RJ, Davis WH, eds. Reconstructive Preprosthetic Oral and Maxillofacial Surgery. Philadelphia, PA: WB Saunders Company; 1995: 165-224.
3. Rees TD. The diabetic dental patient. Dent Clin North Am. 1994; 38: 447-463.
4. Guggenheimer J, Moore PA, Rossie K, et al. Insulin-dependent diabetes mellitus and oral soft tissue pathologies. I. Prevalence and characteristics of non-candidal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Oral Endod. 2000; 89: 563-569.
5. Iacopino AM. Periodontitis and diabetes interrelationships: Role of inflammation. Ann Periodontol. 2001; 6: 125-137.
6. Balshi TJ, Wolfinger GJ. Dental implants in the diabetic patient: A retrospective study. Implant Dent. 1999; 8: 355-359.
7. Olson JW, Shernoff AF, Tarlow JL, et al. Dental endosseous implant assessments in a type 2 diabetic population: A prospective study. Int J Oral Maxillofac Implants. 2000; 15: 811-818.
8. Farzad P, Andersson L, Nyberg J. Dental implant treatment in diabetic patients. Implant Dent. 2002; 11: 262-267.
9. Fiorellini JP, Chen PK, Nevins M, et al. A retrospective study of dental implants in diabetic patients. Int J Periodontics Restorative Dent. 2000; 20: 366-373.
10. Bjursten LM, Emanuelsson L, Ericson LE, et al. A new method for ultrastructural studies of the intact tissue-metal interface. Biomaterials. 1990; 11: 596-601.
11. Thomas DM, Hards DK, Rogers SD, et al. Insulin and bone, clinical and scientific view. Endocrinol Metab North Am. 1997; 4: 5-17.
12. Spanheimer RG, Umpierrez GE, Stumpf V. Decreased collagen production in diabetic rats. Diabetes. 1988; 37: 371-376.
13. Umpierrez GE, Goldstein S, Phillips LS, et al. Nutritional and hormonal regulation of articular collagen production in diabetic animals. Diabetes. 1989; 38: 758-763.
14. Verhaeghe J, Suiker AMH, Nyomba BL, et al. Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology. 1989; 124: 573-582.
15. Takeshita F, Iyama S, Ayukawa Y, et al. The effects of diabetes on the interface between hydroxyapatite implants and bone in rat tibia. J Periodontol. 1997; 68: 180-185.
16. Iyama S, Takeshita F, Ayukawa Y, et al. A study of the regional distribution of bone formed around hydroxyapatite implants in the tibiae of streptozotocin-induced diabetic rats using multiple fluorescent labeling and confocal laser scanning microscopy. J Periodontol. 1997; 68: 1169-1175.
17. Takeshita F, Murai K, Iyama S, et al. Uncontrolled diabetes hinders bone formation around titanium implants in rat tibiae. A light and fluorescence microscopy, and image processing study. J Periodontol. 1998; 69: 314-320.
18. Fiorellini JP, Nevins ML, Norkin A, et al. The effect of insulin therapy on osseointegration in a diabetic rat model. Clin Oral Implants Res. 1999; 10: 362-368.
19. Levy JR, Murray E, Manolagas S, et al. Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. Endocrinology. 1986; 119: 1786-1792.
20. Kream BE, Smith MD, Canalis E, et al. Characterization of the effect of insulin on collagen synthesis in fetal rat bone. Endocrinology. 1985; 116: 296-302.
21. Bembenek ME, Liberti JP. The anabolic effect of insulin on type II collagen synthesis of Swarm rat chondrosarcoma chondrocytes. Arch Biochem Biophys. 1984; 233: 203-211.
22. Thomas DM, Udagawa N, Hards DK, et al. Insulin receptor expression in primary and cultured osteoclast-like cells. Bone. 1998; 23: 181-186.
23. Sun XJ, Rothenberg P, Kahn CR, et al. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 1991; 352: 73-77.
24. Burks DJ, White MF. IRS proteins and ?¸-cell function. Diabetes. 2001; 50: S140-S145.
25. Ogata N, Chikazu D, Kubota N, et al. Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J Clin Invest. 2000; 105: 935-943.
26. Akune T, Ogata N, Hoshi K, et al. Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts. J Cell Biol. 2002; 159: 147-156.
27. Krakauer JC, McKenna MJ, Buderer NF, et al. Bone loss and bone turnover in diabetes. Diabetes. 1995; 44: 775-785.
28. Piepkorn B, Kann P, Forst T, et al. Bone mineral density and bone metabolism in diabetes mellitus. Horm Metab Res. 1997; 29: 584-591.
29. Spanheimer RG. Correlation between decreased collagen production in diabetic animals and in cells exposed to diabetic serum: Response to insulin. Matrix. 1992; 12: 101-107.
30. Glajchen N, Epstein S, Ismail F, et al. Bone mineral metabolism in experimental diabetes mellitus: Osteocalcin as a measure of bone remodeling. Endocrinology. 1988; 123: 290-295.
31. Verhaege J, Suiker AMH, Visser WJ, et al. The effects of systemic insulin, insulin-like growth factor-1 and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. J Endocrinol. 1992; 134: 485-492.