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Diabetes Mellitus and Osteoporosis

  • Diabetes and Other Diseases—Emerging Associations (D Aron, Section Editor)
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Abstract

Diabetes mellitus (particularly type 2) and osteoporosis are two very common disorders, and both are increasing in prevalence. Adolescents with type 1 diabetes mellitus may not reach potential peak bone mass, putting them at greater fracture risk. In adults with type 2 diabetes, fracture risk is increased and is not explained by the bone mineral density measured by dual-energy X-ray absorptiometry, still considered the gold standard predictor of fracture. In this review, we explore potential mechanisms behind the increased fracture risk that occurs in patients with diabetes, even those with increased bone mineral density. One potential link between diabetes and bone is the osteoblast-produced factor, osteocalcin. It remains to be established whether osteocalcin reflects or affects the connection between bone and glucose metabolism. Several other potential mediators of the effects of diabetes on bone are discussed.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. World Health Organization: Diabetes Fact Sheet. Available at www.who.int/mediacentre/factsheets/fs312/en/index.html. Accessed December 2012.

  2. Osteoporosis – General Statistics. Available at www.iofbonehealth.org/facts-statistics#category-14. Accessed December 2012

  3. Bonds D, Larson J, Schwartz A, et al. Risk of fracture in women with type 2 diabetes: the women’s health initiative observational study. J Clin Endocrin Metab. 2006;91:3404–10.

    Article  CAS  Google Scholar 

  4. Strotmeyer E, Cauley J, Schwartz A, et al. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 2005;165:1612–1617.

    Google Scholar 

  5. • Ma L, Oei L, Jiang L, et al. Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol. 2012;27:319–32. This study clearly demonstrates the increased bone density of type 2 diabetes mellitus.

    Article  PubMed  CAS  Google Scholar 

  6. • Nielson CM, Marshall LM, Adams AL, et al. BMI and fracture risk in older men: the osteoporotic fractures in men study (MrOS). J Bone Miner Res. 2011;26:496–502. This prospective study of about 6,000 older men found that obesity was not protective of the skeleton. Indeed fracture risk was higher in obese men.

    Article  PubMed  Google Scholar 

  7. Tanaka S, Kuroda T, Saito M, Shiraki M. Overweight/obesity and underweight are both risk factors for osteoporotic fractures at different sites in Japanese postmenopausal women. Osteoporos Int. 2013;24:69–76.

    Article  PubMed  CAS  Google Scholar 

  8. Viegas M, Costa C, Lopes A, et al. Prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus and their relationship with duration of the disease and chronic complications. J Diabetes Complications. 2011;25:216–21.

    Article  PubMed  Google Scholar 

  9. Compston JE, Watts NB, Chapurlat R, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med. 2011;124:1043–50.

    Article  PubMed  Google Scholar 

  10. Prieto-Alhambra D, Premaor MO, Fina Aviles F, et al. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res. 2012;27:294–300.

    Article  PubMed  Google Scholar 

  11. Premaor MO, Compston JE, Aviles FF, et al. The association between fracture site and obesity in men: a population-based cohort study. J Bone Miner Res epublished 31 January 2013.

  12. de Liefde I, Van der Klift M, de Laet C, et al. Bone mineral density and fracture risk in type 2 diabetes mellitus: the Rotterdam Study. Osteoporosis Int. 2005;16:1713–20.

    Article  Google Scholar 

  13. Lipscombe L, Jamal S, Booth G, et al. The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care. 2007;30:835–41.

    Article  PubMed  Google Scholar 

  14. Bonds D, Larson J, Schwartz A, et al. Risk of fracture in women with type 2 diabetes: the Women’s Health Initiative Observational Study. J Clin Endocrin Metab. 2006;9:3404–10.

    Article  Google Scholar 

  15. Mendez J, Rojano-Mejia D, Pedraza J, et al. Bone mineral density in postmenopausal Mexican-Mestizo women with normal body mass index, overweight, or obesity. Menopause epublished December 30, 2012.

  16. • Kao W, Kammerer C, Schneider J, et al. Type 2 diabetes is associated with increased bone mineral density in Mexican–American women. Arch Med Res. 2003;34:399–406. In women, obesity does not protect bones from fracture.

    Article  PubMed  Google Scholar 

  17. Melton LJ, Riggs BL, Leibson C, et al. A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab. 2008;93:4804–9.

    Article  PubMed  CAS  Google Scholar 

  18. • Burghardt A, Issever A, Schwartz A, et al. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95:5045–55. Using new techniques, the alterations of cortical bone found in type 2 diabetes mellitus may be one explanation for the increased fracture risk.

    Article  PubMed  CAS  Google Scholar 

  19. • Patsch J, Burghardt A, Yap S, et al. Increased cortical porosity in type-2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 2012 10.1002 Epub ahead of print. This study provides information about cortical bone in T1DM.

  20. Kanazawa I, Yamaguchi T, Yamamoto M, et al. Serum osteocalcin is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009;94:45–9.

    Article  PubMed  CAS  Google Scholar 

  21. Gennari L, Merlotti D, Valenti R, et al. Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab. 2012;97(5):1737–44.

    Article  PubMed  CAS  Google Scholar 

  22. Gaudio A, Privitera F, Battaglia K, et al. Sclerostin levels associated with inhibition of the Wnt/β-catenin signaling and reduced bone turnover in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:3744–50.

    Article  PubMed  CAS  Google Scholar 

  23. Garcia-Hernandez A, Arzate H, Gil-Chavarria I, Rojo R, Moreno-Fierros L. High glucose concentrations alter the biomineralization process in human osteoblastic cells. Bone. 2012;50:276–88.

    Article  PubMed  CAS  Google Scholar 

  24. • Booth SL, Centi AM, Smith SR, Gundberg C. The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol. 2013;9:43–55. This review of osteocalcin looks at the potential role of this bone protein in glucose metabolism.

  25. Iglesias P, Arrieta F, Pinera M, et al. Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-Crosslaps in obese subjects with varying degrees of glucose tolerance. Clin Endocrinol. 2011;75:184–8.

    Article  CAS  Google Scholar 

  26. Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int. 2010;21:195–214.

    Article  PubMed  CAS  Google Scholar 

  27. Schwartz AV, Garnero P, Hillier TA, et al. Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab. 2009;94:2380–6.

    Article  PubMed  CAS  Google Scholar 

  28. Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T. Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:1013–9.

    Article  PubMed  CAS  Google Scholar 

  29. Pittas AG, Nelson J, Mitri J, et al. Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. Diabetes Care. 2012;35:565–73.

    Article  PubMed  CAS  Google Scholar 

  30. Harris SS, Pittas AG, Palermo NJ. A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans. Diabetes Obes Metab. 2012;14:789–94.

    Article  PubMed  CAS  Google Scholar 

  31. Lecka-Czernik B. Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary osteoporosis. Curr Osteoporos Rep. 2010;8:178–84.

    Article  PubMed  Google Scholar 

  32. • Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012;27:2231–7. This important review of diabetes and fracture risk includes explanation of how the FRAX risk calculator should be viewed in patients with diabetes.

    Article  PubMed  Google Scholar 

  33. Dunger DB, Acerini CL. IGF-I and diabetes in adolescence. Diabetes Metab. 1999;24:101–7.

    Google Scholar 

  34. Johnson SB, Silverstein J, Rosenbloom A, Carter R, Cunningham W. Assessing daily management in childhood diabetes. Health Psychol. 1986;5:545–64.

    Article  PubMed  CAS  Google Scholar 

  35. Weissberg-Benchell J, Glasgow AM, Tynan WD, et al. J. Adolescent diabetes management and mismanagement. Diabetes Care. 1995;18:77–8.

    Article  PubMed  CAS  Google Scholar 

  36. Albertson AM, Tobelmann RC, Marquart L. Estimated dietary calcium intake and food sources for adolescent females 1980–1992. J Adolesc Health. 1997;20:20–6.

    Article  PubMed  CAS  Google Scholar 

  37. Thrailkill KM. Diabetes care for adolescents. In: Reece EA, Coustan DR, Gabbe SG, editors. Diabetes in women. Philadelphia: Lippincott Williams & Willkins; 2004.

    Google Scholar 

  38. Brown IR, McBain AM, Chalmers J, et al. Sex differences in the relationship of calcium and magnesium excretion to glycaemic control in type 1 diabetes mellitus. Clin Chim Acta. 1999;283:119–28.

    Article  PubMed  CAS  Google Scholar 

  39. Holmes GKT. Screening for coeliac disease in type 1 diabetes. Arch Dis Child. 2002;87:495–9.

    Article  PubMed  CAS  Google Scholar 

  40. Gunczler P, Lanes R, Paz-Martinez V, et al. Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally. J Pediatr Endocrinol Metab. 1998;11:413–9.

    Article  PubMed  CAS  Google Scholar 

  41. Pascual J, Argente J, Lopez MB, et al. Bone mineral density in children and adolescents with diabetes mellitus type 1 of recent onset. Calcif Tissue Int. 1998;62:31–5.

    Article  PubMed  CAS  Google Scholar 

  42. Valerio G, del Puente A, Esposito-del Puente A, et al. The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Horm Res. 2002;58:266–72.

    Article  PubMed  CAS  Google Scholar 

  43. Saha MT, Sievanen H, Salo MK, et al. Bone mass and structure in adolescents with type 1 diabetes compared to healthy peers. Osteoporos Int. 2009;20:1401–6.

    Article  PubMed  CAS  Google Scholar 

  44. Gunczler P, Lanes R, Paoli M, et al. Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2001;14:525–8.

    Article  PubMed  CAS  Google Scholar 

  45. Salvatoni A, Mancassola G, Biasoli R, et al. Bone mineral density in diabetic children and adolescents: a follow-up study. Bone. 2004;34:900–4.

    Article  PubMed  Google Scholar 

  46. Hadjidakis DJ, Raptis AE, Sfakianakis M, Mylonakis A, Raptis SA. Bone mineral density of both genders in type 1 diabetes according to bone composition. J Diabetes Complications. 2006;20:302–7.

    Article  PubMed  Google Scholar 

  47. Hamilton EJ, Rakic V, Davis WA, et al. A five-year prospective study of bone mineral density in men and women with diabetes: The Fremantle Diabetes Study. Acta Diabetol. 2012;49:153–8.

    Article  PubMed  CAS  Google Scholar 

  48. Liu EY, Wactawski-Wende J, Donahue RP, et al. Does Low bone mineral density start in post-teenage years in women with type 1 diabetes? Diabetes Care. 2003;26:2365–9.

    Article  PubMed  Google Scholar 

  49. Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res. 2007;22:1317–28.

    Article  PubMed  CAS  Google Scholar 

  50. Nicodemus KK, Folsom AR. Iowa Women’s Health Study: type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care. 2001;24:1192–7.

    Article  PubMed  CAS  Google Scholar 

  51. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes: a meta-analysis. Osteoporos Int. 2007;18:427–44.

    Article  PubMed  CAS  Google Scholar 

  52. Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004;3:379–89.

    Article  PubMed  CAS  Google Scholar 

  53. Lecka-Czernik B, Gubrij I, Moerman EA, et al. Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2. J Cell Biochem. 1999;74:357–71.

    Google Scholar 

  54. Botolin S, McCabe LR. Inhibition of PPAR-Gamma prevents type I diabetic bone marrow adiposity but not bone loss. J Cell Physiol. 2006;209:967–76.

    Article  PubMed  CAS  Google Scholar 

  55. Lechleitner M, Koch T, Herold M, Dzien A, Hoppichler F. Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk. J Intern Med. 2000;248:67–76.

    Article  PubMed  CAS  Google Scholar 

  56. • Coe LM, Irwin R, Lippner D, McCabe LR. The bone marrow microenvironment contributes to type I diabetes induced osteoblast death. J Cell Physiol. 2011;226:477–83. This study provides insight into how diabetes affects osteoblasts.

    Article  PubMed  CAS  Google Scholar 

  57. Maor G, Karnieli E. The insulin-sensitive glucose transporter (GLUT4) is involved in early bone growth in control and diabetic mice, but is regulated through the insulin-like growth factor I receptor. Endocrinology. 1999;140:1841–51.

    Article  PubMed  CAS  Google Scholar 

  58. Nixon AJ, Lillich JT, Burton-Wurster N, et al. Differentiated cellular function in fetal chondrocytes cultured with insulin-like growth factor-I and transforming growth factor-beta. J Orthop Res. 1998;16:531–41.

    Article  PubMed  CAS  Google Scholar 

  59. Wan Y, Chong LW, Evans RM. PPAR-Gamma regulates osteoclastogenesis in mice. Nat Med. 2007;13:1496–503.

    Article  PubMed  CAS  Google Scholar 

  60. Williams JP, Blair HC, McDonald JM, et al. Regulation of osteoclastic bone resorption by glucose. Biochem Biophys Res Commun. 1997;235:646–51.

    Article  PubMed  CAS  Google Scholar 

  61. Fraser JH, Helfrich MH, Wallace HM, Ralston SH. Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae. Bone. 1996;19:223–6.

    Article  PubMed  CAS  Google Scholar 

  62. Pater A, Sypniewska, Pilecki O. Biochemical markers of bone cell activity in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2010;23:81–6.

    Article  PubMed  CAS  Google Scholar 

  63. Hill PA, Tumber A, Meikle MC. Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology. 1997;138:3849–58.

    Article  PubMed  CAS  Google Scholar 

  64. Thomas DM, Udagawa N, Hards DK, et al. Insulin receptor expression in primary and cultured osteoclast-like cells. Bone. 1998;23:181–6.

    Article  PubMed  CAS  Google Scholar 

  65. Conover CA, Lee PD, Riggs BL, Powell DR. Insulin-like growth factor-binding protein-1 expression in cultured human bone cells: regulation by insulin and glucocorticoid. Endocrinology. 1996;137:3295–301.

    Article  PubMed  CAS  Google Scholar 

  66. Moyer-Mileur LJ, Slater H, Jordan KC, Murray MA. IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes. J Bone Miner Res. 2008;23:1884–91.

    Article  PubMed  CAS  Google Scholar 

  67. Pastor MMC, Lopez-Ibarra PJ, Escobar-Jimenez F, et al. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int. 2000;11:455–9.

    Article  Google Scholar 

  68. Bierhaus A, Schiekofer S, Schwaninger M, et al. Diabetes-associated sustained activation of the transcription factor nuclear-kappa B. Diabetes. 2001;50:2792–808.

    Article  PubMed  CAS  Google Scholar 

  69. Lindsey JB, Cipollone F, Abdullah SM, McGuire DK. Receptor for advanced glycation endproducts (RAGE) and soluble RAGE (sRAGE): cardiovascular implications. Diab Vasc Dis Res. 2009;6:7–14.

    Article  PubMed  Google Scholar 

  70. Zhang Y, Papasian CJ, Deng HW. Alterations of vitamin D metabolic enzyme expression and calcium transporter abundance in kidney involved in type 1 diabetes-induced bone loss. Osteoporos Int. 2011;22:1781–8.

    Article  PubMed  CAS  Google Scholar 

  71. Bronsky J, Prusa R. Amylin fasting plasma levels are decreased in patients with osteoporosis. Osteoporos Int. 2004;15:243–7.

    Article  PubMed  CAS  Google Scholar 

  72. Horcajada-Molteni MN, Chanteranne B, Lebecque P, et al. Amylin and bone metabolism in streptozotocin-induced diabetic rats. J Bone Miner Res. 2001;16:958–65.

    Article  PubMed  CAS  Google Scholar 

  73. Takeda S, Elefteriou F, Levasseur R, et al. Leptin regulates bone via the sympathetic nervous system. Cell. 2002;111:305–17.

    Article  PubMed  CAS  Google Scholar 

  74. Ducy P, Karsenty G. The two faces of serotonin in bone biology. J Cell Biol. 2010;191:7–13.

    Article  PubMed  CAS  Google Scholar 

  75. Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.

    Article  PubMed  CAS  Google Scholar 

  76. Kawai M, Devlin MJ, Rosen CJ. Fat targets for skeletal health. Nat Rev Rheumatol. 2009;5:365–72.

    Article  PubMed  Google Scholar 

  77. Hedbacker K, Birsoy K, Wysocki RW, et al. Antidiabetic effects of IGFBP2, a leptin-regulated gene. Cell Metab. 2010;11:11–22.

    Article  PubMed  CAS  Google Scholar 

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Conflict of Interest

Robert Sealand declares that he has no conflict of interest.

Christie Razavi declares that she has no conflict of interest.

Robert A. Adler has been a consultant for Amgen. He has received grant support from Merck, Eli Lily, Novartis, Genentech, and Amgen. He receives royalties from Springer as a book editor, and he is a section editor for the Springer journal Current Osteoporosis Reports. He is also on the Council of the American Society for Bone and Mineral Research.

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Sealand, R., Razavi, C. & Adler, R.A. Diabetes Mellitus and Osteoporosis. Curr Diab Rep 13, 411–418 (2013). https://doi.org/10.1007/s11892-013-0376-x

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