The beneficial roles of insulin and parathyroid hormones in the treatment of experimentally induced diabetic osteoporosis in female rats: bone mineral density, morphometric and histological studies

• Autorzy: Abd El Aziz G.S. , Ramadan W.S. , El-Fark M.O. , Saleh H.A.M.
• Języki publikacji: EN

Abstrakty

EN

Background: Diabetes mellitus (DM) and osteoporosis are two frequent medical conditions with an increasing prevalence in elderly people and are responsible for large number of incurable fractures. This study is designed experimentally in female rats in order to determine whether combined treatment of insulin and parathyroid hormone (PTH) enhances the reversibility of the osteoporotic changes that occurred in streptozotocin (STZ)-induced DM. Materials and methods: In this study, 30 adult female rats aged 3 months were used, they were randomly divided into: control group (6 rats) and diabetes group (24 rats), in which experimental DM was induced by i.p. injection of a single dose of STZ (60 mg/kg/body weight). Diabetic group was further divided into four subgroups (6 rats each): non-treated diabetic, insulin-treated (8–12 units s.c./day of Humalin U-40), PTH-treated (6.0 μg s.c./kg/day) and combined insulin and PTH-treated subgroups. All tested groups were assessed for body weight, food and water consumptions. Results: At the end of the experimental period, the bone mineral density (BMD) was measured for all rats of different groups; then the rats were sacrificed and blood samples were collected for measuring glucose, alkaline phosphatase and osteocalcin levels. Right femora were dissected out and subjected to measurement of diameter of neck and shaft, length of shaft, and weight. Then the femora specimens were processed and stained with haematoxylin and eosin for histological study. The results showed that there was a statistically significant, decrease in BMD, increase in the level of alkaline phosphate, and decrease in the level of osteocalcin in rats in diabetic group compared with other groups; these parameters improved in other groups, especially in diabetes/insulin/PTH group. The rats in diabetic group showed statistically significant decrease in neck and shaft diameters and weight of femur bone compared with other groups, while rats in diabetes/insulin/PTH group showed a significant improvement of these parameters. In diabetic group, there were different histopathological changes in cortical bone and Haversian canals, which improved in other groups, especially in rats in diabetes/insulin/PTH group. Conclusions: The untreated DM resulted in dramatic reduction in BMD and morphometric parameters. Treatment with insulin ameliorated these effects to some extent, while PTH co- -treatment had a more positive effect. The combination of PTH and insulin resulted in stronger improvement of all parameters to approximately like those of control rats. (Folia Morphol 2016; 75, 3: 341–354)

• Wydawca: -
• Czasopismo: Folia Morphologica
• Rocznik: 2016
• Tom: 75
• Numer: 3
• Opis fizyczny: p.341-354,fig.,ref.

Twórcy

autor

Abd El Aziz G.S.

• Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

autor

Ramadan W.S.

• Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

autor

El-Fark M.O.

• Department of Anatomy, Faculty of Medicine, King Abdulaziz University, P.O.Box: 80205, Jeddah 21589, Saudi Arabia
• Department of Anatomy, Faculty of Medicine, Suez Canal University, Egypt

autor

Saleh H.A.M.

• Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Bibliografia

• 1. Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi Sh, Farhangi A, Allah Verdi A, Mofidian SMA, Lame Rad B (2007) Induction of diabetes by streptozotocin in rats. Indian J Clin Bioch, 22: 60–64.
• 2. Aleksynienė R, Hvid I (2004) Parathyroid hormone: possible future drug for orthopedic surgery. Medicina (Kaunas, Lithuania), 40: 842–849.
• 3. American Diabetes Association (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care, 32: 62–67.
• 4. Andreassen TT, Ejersted C, Oxlund H (1999) Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res, 14: 960–968.
• 5. Barnes GL, Kakar S, Vora S, Morgan EF, Gerstenfeld LC, Einhorn TA (2008) Stimulation of fracture-healing with systemic intermittent parathyroid hormone treatment. J Bone Joint Surg Am, 90: 120–127.
• 6. Bayat M, Abdi S, Javadieh F, Mohsenifar Z, Rashid MR (2009) The effects of low-level laser therapy on bone in diabetic and no diabetic rats. Photomed Laser Surg, 27: 703–708.
• 7. Beam H, Parsons J, Lin S (2002) The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus. J Orthop Res, 20: 1210–1216.
• 8. Botolin S, McCabe LR (2007) Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice. Endocrinology, 148: 198–205.
• 9. Brown SA, Sharpless JL (2004) Osteoporosis: an under-appreciated complication of diabetes. Clinical Diabetes, 22: 10–20.
• 10. Chau DL, Edelman SV (2002) Osteoporosis and diabetes. Clin Diabetes, 20: 153–157.
• 11. Chau DL, Edelman SV, Chandran M (2003) Osteoporosis and diabetes. Curr Diabet Rep, 3: 37–42.
• 12. Chen H, Tian X, Liu X, Setterberg RB, Li M, Jee WSS (2008) Alfa calcidol-stimulated focal bone formation on the cancellous surface and increased bone formation on the periosteal surface of the lumbar vertebrae of adult female rats. Calcif Tissue Int, 82: 127–136.
• 13. Devesh C, Kritika M, Anroop N, Kumar SP, Sumeet G (2012) Spirulina reverses histomorphological changes in diabetic osteoporosis in Pioglitazone treated rats. J Diabetes Metab, S1: 1–7.
• 14. Dobnig H, Turner RT (1997) The effects of programmed administration of human parathyroid hormone fragment (l-34) on bone histomorphometry and serum chemistry in rats. Endocrinology, 138: 4607–4612.
• 15. Follak N, Kloting I, Wolf E, Merk H (2004a) Histomorphometric evaluation of the influence of the diabetic metabolic state on bone defect healing depending on the defect size in spontaneously diabetic BB/OK rats. Bone, 35: 144–152.
• 16. Follak N, Kloting I, Wolf E, Merk H (2004b) Improving metabolic control reverses the histomorphometric and biomechanical abnormalities of an experimentally induced bone defect in spontaneously diabetic rats. Calcif Tissue Int, 74: 551–560.
• 17. Fowlkes JL, Bunn RC, Liu L,Wahl EC, Coleman HN, Cockrell GE, Perrien DS, Lumpkin CK Jr, Thrailkill KM (2008) Runt-related transcription factor 2 (RUNX2) and RUNX2-related osteogenic genes are down-regulated throughout osteogenesis in type 1 diabetes mellitus. Endocrinology, 149: 1697–1704.
• 18. Funk JR, Hale JE, Carmines D, Gooch HL, Hurwitz SR (2000) Biomechanical evaluation of early fracture healing in normal and diabetic rats. J OrthopedicRes, 18: 126–132.
• 19. Gandhi A, Beam HA, O’Connor JP, Parsons JR, Lin SS (2005) The effects of local insulin delivery on diabetic fracture healing. Bone, 37: 482–490.
• 20. Havel PJ, Hahn TM, Sindelar DK, Baskin DG, Dallman MF, Weigle DS, Schwartz MW (2000) Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. Diabetes, 49: 243–252.
• 21. He H, Liu R, Desta T, Leone C, Gerstenfeld LC, Graves DT (2004) Diabetes causes decreased osteoclastogenesis, reduced bone formation and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss. Endocrinology, 145: 447–452.
• 22. Hofbauer LC, Brueck CC, Singh SK, Dobnig H (2007) Osteoporosis in patients with diabetes mellitus. J Bone Mineral Res, 22: 1317–1318.
• 23. Holzhausen M, Garcia DF, Pepato MT, Marcantonio E (2004) The influence of short-term diabetes mellitus and insulin therapy on alveolar bone loss in rats. J Periodont Res, 39: 188–193.
• 24. Ikeda T, Manabe H, Iwata K (2004) Clinical significance of alendronate in postmenopausal type 2 diabetes mellitus. Diabetes Metab, 30: 355–358.
• 25. Inzerillo AM, Epstein S (2004) Osteoporosis and diabetes mellitus. Rev Endocr Metab Disord, 5: 261–268.
• 26. 26. Jackuliak P, Payer J (2014) Osteoporosis, fractures, and diabetes: review article. Int J Endocrinol, 2014: 820615.
• 27. Jahng JS, Kim HW (2000) Effect of intermittent administration of parathyroid hormone on fracture hea1ing in ovariectomized rats. Orthopedics, 23: 1089–1094.
• 28. Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol, 166: 495–505.
• 29. Jilka RL, O’Brien CA, Bartell SM, Weinstein RS, Manolagas SC (2010) Continuous elevation of PTH increases the number of osteoblasts via both osteoclast-dependent and independent mechanisms. J Bone Miner Res, 25: 2427–2437.
• 30. Kasukawa Y, Miyakoshi N, Itoi E, Tsuchida T, Tamura Y, Kudo T, Suzuki K, Seki A, Sato K (2004) Effects of h-PTH on cancellous bone mass, connectivity and bone strength in ovariectomized rats with and without sciatic neurectomy. J Orthop Res, 22: 457–464.
• 31. Khamaisi M, Regev E, Yarom N, Avni B, Leitersdorf E, Raz I, Elad S (2007) Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab, 92: 1172–1175.
• 32. Liu Z, Aronson J, Wahl EC, Liu L, Perrien DS, Kern PA, Fowlkes JL, Thrailkill KM, Bunn RC, Cockrell GE, Skinner RA, Lumpkin CK Jr (2007) A novel rat model for the study of deficits in bone formation in type-2 diabetes. Acta Orthopaedica, 78: 46–55.
• 33. Lopez Ibarra PJ, Pastor MM, Escobar Jimenez F, Pardo MD, Gonzalez AG, Luna JD, Requena ME, Diosdado MA (2001) Bone mineral density at time of clinical diagnosis of adultonset type 1 diabetes mellitus. Endocr Pract, 7: 346–351.
• 34. Lozano D, De Castro LF, Dapia S, Andrade Zapata I, Manzarbeitia F, Alvarez Arroyo MV, Gómez-Barrena E, Esbrit P (2009) Role of parathyroid hormone-related protein in the decreased osteoblast function in diabetes-related osteopenia. Endocrinology, 150: 2027–2035.
• 35. Makino H, Tanaka I, Mukoyama M, Sugawara A, Mori K, Muro S, Suganami T, Yahata K, Ishibashi R, Ohuchida S, Maruyama T, Narumiya S, Nakao K (2002) Prevention of diabetic nephropathy in rats by prostaglandin E receptor EP I-selective antagonist. Am Soc Nephrol, 13: 1757–1765.
• 36. Mashiba T, Burr DB, Turner CH, Sato M, Cain RL, Hock JM (2001) Effects of human parathyroid hormone (I-34), LY333334, on bone mass, remodeling, and mechanical properties of cortical bone during the first remodelling cycle in rabbits. Bone, 28: 538–547.
• 37. McCabe LR (2007) Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem, 102: 1343–1357.
• 38. Miyakoshi N, Kasukawa Y, Linkhart TA, Baylink DJ, Mohan S (2001) Evidence that anabolic effects of PTH on bone require IGF-I in growing mice. Endocrinology, 142: 4349–4356.
• 39. Moshref SS (2007) PM 701 a highly selective anti cancerous agent against L1210 leukemic cells: In vivo clinical and histopathological study. J KAU Med Sci, 14: 85–99.
• 40. Motyl KJ, McCauley LK, McCabe LR (2012) Amelioration of type I diabetes-induced osteoporosis by parathyroid hormone is associated with improved osteoblast survival. J Cell Physiol, 227: 1326–1334.
• 41. Nakazawa T, Nakajima A, Shiomi K, Moriya H, Einhorn TA, Yamazaki M (2005) Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1-34) on chondrogenesis in. a model of experimental fracture healing. Bone, 37: 711–719.
• 42. Nicodemus KK, Folsom AR (2001) Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care, 24: 1192–1197.
• 43. Reddy GK, Stehno-Bittel L, Hamade S, Enwemeka CS (2001) The biomechanical integrity of bone in experimental diabetes. Diabetes Research and Clinical Practice, 54: 1–8.
• 44. Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: Thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum, 60: 3346–3355.
• 45. Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int, 17: 1514–1523.
• 46. Santana RB, Xu L, Chase HB, Amar S, Graves DT, Trackman PC (2003) A role for advanced glycation end products in diminished bone healing in type of 47 diabetes. Diabetes, 52: 1502–1510.
• 47. Schwartz AV (2003) Diabetes mellitus: Does it affect bone? Calcif Tissue Int, 73: 515–519.
• 48. Silva MJ, Brodt MD, Lynch MA, McKenzie JA, Tanouye KM, Nyman JS, Wang X (2009) Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth and diminished whole bone strength and fatigue life. J Bone Mineral Res, 24: 1618–1627.
• 49. Sosa M, Dominguez M, Navarro MC, Segarra MC, Hernandez D, de Pablos P, Betancor P (1996) Bone mineral metabolism is normal in non-insulin-dependent diabetes mellitus. J Diabetes Complications, 10: 201–205.
• 50. Sulayman AA (2007) Effect of water soluble soybean fiber (WSSF) on bone changes induced by ovariectomy in female albino rat: a light and scanning electron microscopic study. Egypt J Histol, 30: 221–232.
• 51. Suzuki K, Miyakoshi N, Tsuchida T, Kasukawa Y, Sato K, Itoi E (2003) Effects of combined treatment of insulin and human parathyroid hormone (1-34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats. Bone, 33: 108–114.
• 52. Suzuki K, Kurose T, Takizawa M, Maruyama M, Ushikawa K, Kikuyama M, Sugimoto C, Seino Y, Nagamatsu S, Ishida H (2005) Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density. Diabetes Res Clin Pract, 68: 117–125.
• 53. Thrailkill KM, Liu L, Wahl EC, Bunn RC, Perrien DS, Cokrell GE, Skinner RA, Hogue WR, Carver AA, Fowlkes JL, Aronson J, Lumpkin CK Jr (2005). Bone formation is impaired in a model of type 1 diabetes. Diabetes, 54: 2875–2881.
• 54. Torres-Duran PV, Ferreira-Hermosillo A, Juarez-Oropeza MA (2007) Antihyper-lipedemic and antihypertensive effects of spirulina maxima in an open sample of Mexican population: a preliminary report. Lipids Health Dis, 6: 33.
• 55. Tsuchida T, Sato K, Miyakoshi N, Abe T, Kudo T, Tamura Y, Kasukawa Y, Suzuki K (2000) Histomorphometric evaluation of the recovering effects of human parathyroid hormone (1-34) on bone structure and turnover in streptozotocininduced diabetic rats. Calcif Tissue Int, 66: 229–233.
• 56. Tsuchida T, Miyakosm N, Kudo T, Tamura Y, Kasukawa Y, Suzuki K, Sato K (2001) Restoring effects of human parathyroid hormone (1-34) on trabecular connectivity in ovariectomized rats. Tohoku J Exp Med, 194: 213–221.
• 57. Turner RB, Vagula M, Devi SS (2009) Osteoporosis: An understated complication of diabetes. US Pharm, 34: 14–16.
• 58. Uchiyama S, Yamaguchi M (2005) Oral administration of beta-cryptoxanthin prevents bone loss in streptozotocindiabetic rats in vivo. Biol Pharm Bull, 28: 1766–1769.
• 59. Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore MS, Linda Y, Nold JB (2002) Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. Toxicol Pathol, 30: 312–321.
• 60. Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 27: 1047–1053.
• 61. World Health Organization. Diabetes. Fact sheet No. 312. November 2008. www.who.int/mediacentre/factsheets/fs312/en/. Accessed April 2, 2009.
• 62. Young B, Lowe JO, Stevens A, Heath JW (2005) Wheater’s functional histology. 5th Ed. Churchill Livingstone, Philadelphia.

Identyfikatory

DOI

10.5603/FM.a2015.0129