Bone and Diabetes

  • Andrea Palermo
  • Anda Mihaela Naciu
  • Gaia Tabacco
  • Luca D’Onofrio
  • Nicola Napoli


Diabetes is a metabolic disease characterized by high blood glucose levels resulting from impaired insulin production or insulin resistance or both. It has been well established that bone fragility is a new complication of diabetes, particularly of type 1 diabetes (T1D) [1]. Diabetes may negatively affect bone health by unbalancing several processes and systems: bone formation, bone resorption, collagen formation and collagen cross-linking, secretion of inflammatory cytokines, skeletal muscle, incretin system, bone marrow adiposity, calcium metabolism, etc.


  1. 1.
    Hough S, Pierroz D, Cooper C, Ferrari S. Mechanisms in endocrinology: mechanisms and evaluation of bone fragility in type 1 diabetes mellitus. Eur J Endocrinol. 2016;174(4):R127–38. Scholar
  2. 2.
    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. Scholar
  3. 3.
    Ahmed LA, Joakimsen RM, Berntsen GK, Fønnebø V, Schirmer H. Diabetes mellitus and the risk of non-vertebral fractures: the Tromsø study. Osteoporos Int. 2006;17:495–500. Scholar
  4. 4.
    Miao J, Brismar K, Nyrén O, Ugarph-Morawski A, Ye W. Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care. 2005;28:2850–5. Scholar
  5. 5.
    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. Scholar
  6. 6.
    Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166:495–505. Scholar
  7. 7.
    Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia. 2005;48:1292–9. Scholar
  8. 8.
    Zhukouskaya VV, Eller-Vainicher C, Vadzianava VV, Shepelkevich AP, Zhurava IV, Korolenko GG, et al. Prevalence of morphometric vertebral fractures in patients with type 1 diabetes. Diabetes Care. 2013;36:427–44. Scholar
  9. 9.
    Shah VN, Shah CS, Snell-Bergeon JK. Type 1 diabetes and risk of fracture: meta-analysis and review of the literature. Diabet Med. 2015;32:1134–42. Scholar
  10. 10.
    Weber DR, Haynes K, Leonard MB, Willi SM, Denburg MR. Type 1 diabetes is associated with an increased risk of fracture across the life span: a population-based cohort study using The Health Improvement Network (THIN). Diabetes Care. 2015;38:1913–20. Scholar
  11. 11.
    Shanbhogue VV, Mitchell DM, Rosen CJ, Bouxsein ML, Leslie W, Rubin M, et al. Type 2 diabetes and the skeleton: new insights into sweet bones. Lancet Diabetes Endocrinol. 2016;4:159–73. Scholar
  12. 12.
    Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, 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;165:1612–7. Scholar
  13. 13.
    Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, et al. Risk of fracture in women with type 2 diabetes: the women’s health initiative observational study. J Clin Endocrinol Metab. 2006;91:3404–10. Scholar
  14. 14.
    Koh W-P, Wang R, Ang L-W, Heng D, Yuan J-M, Yu MC, et al. Diabetes and risk of hip fracture in the Singapore Chinese health study. Diabetes Care. 2010;33:213–5. Scholar
  15. 15.
    Looker AC, Eberhardt MS, Saydah SH, Janghorbani M, Van Dam RM, Willett WC, et al. Diabetes and fracture risk in older U.S. adults. Bone. 2007;82:9–15. Scholar
  16. 16.
    Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K. Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int. 2006;17:1065–77. Scholar
  17. 17.
    Melton LJ, Leibson CL, Achenbach SJ, Therneau TM, Khosla S. Fracture risk in type 2 diabetes: update of a population-based study. J Bone Miner Res. 2008;23:1334–42. Scholar
  18. 18.
    Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, et al. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab. 2001;86:32–8. Scholar
  19. 19.
    Pun KK, Lau P, Ho PW. The characterization, regulation, and function of insulin receptors on osteoblast-like clonal osteosarcoma cell line. J Bone Miner Res. 1989;4:853–62. Scholar
  20. 20.
    Cornish J, Callon KE, Reid IR. Insulin increases histomorphometric indices of bone formation in vivo. Calcif Tissue Int. 1996;59:492–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Ogata N, Chikazu D, Kubota N, Terauchi Y, Tobe K, Azuma Y, et al. Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J Clin Invest. 2000;105:935–43. Scholar
  22. 22.
    Hie M, Tsukamoto I. Increased expression of the receptor for activation of NF-kappaB and decreased runt-related transcription factor 2 expression in bone of rats with streptozotocin-induced diabetes. Int J Mol Med. 2010;26:611–8.PubMedGoogle Scholar
  23. 23.
    Campos Pastor MM, López-Ibarra PJ, Escobar-Jiménez F, Serrano Pardo MD, García-Cervigón AG. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int. 2000;11:455–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Xiang G, Sun H, Zhao L. Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients. Diabetes Res Clin Pract. 2007;76:199–206. Scholar
  25. 25.
    Hsu C-N, Chang C-H, Lin Y-S, Lin J-W, Caffrey JL. Association of serum C-peptide concentrations with cancer mortality risk in pre-diabetes or undiagnosed diabetes. PLoS One. 2013;8:e55625. Scholar
  26. 26.
    Montalcini T, Gallotti P, Coppola A, Zambianchi V, Fodaro M, Galliera E, et al. Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes. Osteoporos Int. 2015;26:1639–46. Scholar
  27. 27.
    Yamaguchi T, Kanazawa I, Yamamoto M, Kurioka S, Yamauchi M, Yano S, et al. Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes. Bone. 2009;45:174–9. Scholar
  28. 28.
    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. Scholar
  29. 29.
    Fulzele K, DiGirolamo DJ, Liu Z, Xu J, Messina JL, Clemens TL. Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action. J Biol Chem. 2007;282:25649–58. Scholar
  30. 30.
    Lee YH, White MF. Insulin receptor substrate proteins and diabetes. Arch Pharm Res. 2004;27:361–70.CrossRefPubMedGoogle Scholar
  31. 31.
    Ardawi MS, Akhbar DH, Alshaikh A, Ahmed MM, Qari MH, Rouzi AA, et al. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone. 2013;56:355–62. Scholar
  32. 32.
    Barrett-Connor E, Kritz-Silverstein D. Does hyperinsulinemia preserve bone? Diabetes Care. 1996;19:1388–92.CrossRefPubMedGoogle Scholar
  33. 33.
    Stolk RP, Van Daele PL, Pols HA, Burger H, Hofman A, Birkenhäger JC, et al. Hyperinsulinemia and bone mineral density in an elderly population: the Rotterdam study. Bone. 1996;18:545–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Choi YJ, Kim DJ, Lee Y, Chung Y-S. Insulin is inversely associated with bone mass, especially in the insulin-resistant population: the Korea and US national health and nutrition examination surveys. J Clin Endocrinol Metab. 2014;99:1433–41. Scholar
  35. 35.
    Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142:309–19. Scholar
  36. 36.
    Abrahamsen B, Rohold A, Henriksen JE, Beck-Nielsen H. Correlations between insulin sensitivity and bone mineral density in non-diabetic men. Diabet Med. 2000;17:124–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Shin D, Kim S, Kim KH, Lee K, Park SM. Association between insulin resistance and bone mass in men. J Clin Endocrinol Metab. 2014;99:988–95. Scholar
  38. 38.
    Hie M, Iitsuka N, Otsuka T, Tsukamoto I. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. Int J Mol Med. 2011;28:455–62. Scholar
  39. 39.
    Okazaki K, Yamaguchi T, Tanaka K-I, Notsu M, Ogawa N, Yano S, et al. Advanced glycation end products (AGEs), but not high glucose, inhibit the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression, and inhibit cell growth and increasing cell apoptosis. Calcif Tissue Int. 2012;91:286–96. Scholar
  40. 40.
    Kim JH, Kim Y-Y, Kim S-J. High glucose inhibits gene expression of tyrosyl-tRNA synthetase in osteoblast cells. Methods Find Exp Clin Pharmacol. 2009;31:639–44. Scholar
  41. 41.
    Villarino ME, Sánchez LM, Bozal CB, Ubios AM. Influence of short-term diabetes on osteocytic lacunae of alveolar bone. A histomorphometric study. Acta Odontológica Latinoam AOL. 2006;19:23–8.Google Scholar
  42. 42.
    Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, et al. Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab. 2012;97:1737–44. Scholar
  43. 43.
    Neumann T, Hofbauer LC, Rauner M, Lodes S, Kästner B, Franke S, et al. Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus. Clin Endocrinol. 2014;80:649–55. Scholar
  44. 44.
    Wittrant Y, Gorin Y, Woodruff K, Horn D, Abboud HE, Mohan S, et al. High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis. Bone. 2008;42:1122–30. Scholar
  45. 45.
    Hie M, Shimono M, Fujii K, Tsukamoto I. Increased cathepsin K and tartrate-resistant acid phosphatase expression in bone of streptozotocin-induced diabetic rats. Bone. 2007;41:1045–50. Scholar
  46. 46.
    Saito M, Soshi S, Tanaka T, Fujii K. Intensity-related differences in collagen post-translational modification in MC3T3-E1 osteoblasts after exposure to low- and high-intensity pulsed ultrasound. Bone. 2004;35:644–55. Scholar
  47. 47.
    Saito M, Marumo K. Bone quality in diabetes. Front Endocrinol (Lausanne). 2013;4:72. Scholar
  48. 48.
    Turecek C, Fratzl-Zelman N, Rumpler M, Buchinger B, Spitzer S, Zoehrer R, et al. Collagen cross-linking influences osteoblastic differentiation. Calcif Tissue Int. 2008;82:392–400. Scholar
  49. 49.
    Raposo B, Rodríguez C, Martínez-González J, Badimon L. High levels of homocysteine inhibit lysyl oxidase (LOX) and downregulate LOX expression in vascular endothelial cells. Atherosclerosis. 2004;177:1–8. Scholar
  50. 50.
    Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012;27:2231–7. Scholar
  51. 51.
    Cui S, Xiong F, Hong Y, Jung J-U, Li X-S, Liu J-Z, et al. APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age-dependent manner. J Bone Miner Res. 2011;26:1084–98. Scholar
  52. 52.
    Zhou Z, Han J-Y, Xi C-X, Xie J-X, Feng X, Wang C-Y, et al. HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. J Bone Miner Res. 2008;23:1084–96. Scholar
  53. 53.
    Saito M, Fujii K, Mori Y, Marumo K. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int. 2006;17:1514–23. Scholar
  54. 54.
    Silva MJ, Brodt MD, Lynch MA, McKenzie JA, Tanouye KM, Nyman JS, et al. 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 Miner Res. 2009;24:1618–27. Scholar
  55. 55.
    Okazaki R, Totsuka Y, Hamano K, Ajima M, Miura M, Hirota Y, et al. Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab. 1997;82:2915–20. Scholar
  56. 56.
    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. Scholar
  57. 57.
    Dorrian CA, Cathcart S, Clausen J, Shapiro D, Dominiczak MH. Factors in human serum interfere with the measurement of advanced glycation endproducts. Cell Mol Biol (Noisy-le-Grand). 1998;44:1069–79.Google Scholar
  58. 58.
    Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132:2131–57. Scholar
  59. 59.
    Zhong Q, Itokawa T, Sridhar S, Ding K-H, Xie D, Kang B, et al. Effects of glucose-dependent insulinotropic peptide on osteoclast function. Am J Physiol Endocrinol Metab. 2007;292:E543–8. Scholar
  60. 60.
    Nissen A, Christensen M, Knop FK, Vilsbøll T, Holst JJ, Hartmann B. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans. J Clin Endocrinol Metab. 2014;99:E2325–9. Scholar
  61. 61.
    Faienza MF, Luce V, Ventura A, Colaianni G, Colucci S, Cavallo L, et al. Skeleton and glucose metabolism: a bone-pancreas loop. Int J Endocrinol. 2015;2015:758148. Scholar
  62. 62.
    Nuche-Berenguer B, Portal-Núñez S, Moreno P, González N, Acitores A, López-Herradón A, et al. Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor. J Cell Physiol. 2010;225:585–92. Scholar
  63. 63.
    Jeon YK, Bae MJ, Kim JI, Kim JH, Choi SJ, Kwon SK, et al. Expression of glucagon-like peptide 1 receptor during Osteogenic differentiation of adipose-derived stem cells. Endocrinol Metab (Seoul). 2014;29:567–73. Scholar
  64. 64.
    Gilbert MP, Pratley RE. The impact of diabetes and diabetes medications on bone health. Endocr Rev. 2015;36:194–213. Scholar
  65. 65.
    Nuche-Berenguer B, Moreno P, Esbrit P, Dapía S, Caeiro JR, Cancelas J, et al. Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcif Tissue Int. 2009;84:453–61. Scholar
  66. 66.
    Mansur SA, Mieczkowska A, Bouvard B, Flatt PR, Chappard D, Irwin N, et al. Stable incretin mimetics counter rapid deterioration of bone quality in type 1 diabetes mellitus. J Cell Physiol. 2015;230:3009–18. Scholar
  67. 67.
    Zhao Y, Kachroo S, Kawabata H, Colilla S, Mukherjee J, Fonseca V, et al. Association between hypoglycemia and fall-related fractures and health care utilization in older veterans with type 2 diabetes. Endocr Pract. 2016;22:196–204. Scholar
  68. 68.
    Khan TS, Fraser L-A. Type 1 diabetes and osteoporosis: from molecular pathways to bone phenotype. J Osteoporos. 2015;2015:174186. Scholar
  69. 69.
    Formiga F, Chivite D, Ruiz D, Navarro M, Perez Castejon JM, Duaso E, et al. Clinical evidence of diabetes mellitus end-organ damage as risk factor for falls complicated by hip fracture: a multi-center study of 1225 patients. Diabetes Res Clin Pract. 2015;109:233–7. Scholar
  70. 70.
    Shanbhogue VV, Hansen S, Frost M, Jørgensen NR, Hermann AP, Henriksen JE, et al. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease. Eur J Endocrinol. 2015;174:115–24. Scholar
  71. 71.
    Jules J, Feng X. In vitro investigation of the roles of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1 in murine osteoclastogenesis. Methods Mol Biol. 2014;1155:109–23. Scholar
  72. 72.
    Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13:156–63. Scholar
  73. 73.
    Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G, et al. Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci U S A. 2001;98:13960–5. Scholar
  74. 74.
    Kristiansen OP, Mandrup-Poulsen T. Interleukin-6 and diabetes: the good, the bad, or the indifferent? Diabetes. 2005;54(Suppl 2):S114–24.CrossRefPubMedGoogle Scholar
  75. 75.
    Park JH, Park KH, Cho S, Choi YS, Seo SK, Lee BS, et al. Concomitant increase in muscle strength and bone mineral density with decreasing IL-6 levels after combination therapy with alendronate and calcitriol in postmenopausal women. Menopause. 2013;20:747–53. Scholar
  76. 76.
    Taguchi Y, Yamamoto M, Yamate T, Lin SC, Mocharla H, DeTogni P, et al. Interleukin-6-type cytokines stimulate mesenchymal progenitor differentiation toward the osteoblastic lineage. Proc Assoc Am Physicians. 1998;110:559–74.PubMedGoogle Scholar
  77. 77.
    Nouh MR, Eid AF. Magnetic resonance imaging of the spinal marrow: basic understanding of the normal marrow pattern and its variant. World J Radiol. 2015;7:448–58. Scholar
  78. 78.
    Patsch JM, Li X, Baum T, Yap SP, Karampinos DC, Schwartz AV, et al. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res. 2013;28:1721–8. Scholar
  79. 79.
    Piccinin MA, Khan ZA. Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications. Adipocytes. 2014;3:263–72. Scholar
  80. 80.
    Krause MP, Riddell MC, Gordon CS, Imam SA, Cafarelli E, Hawke TJ. Diabetic myopathy differs between Ins2Akita+/− and streptozotocin-induced type 1 diabetic models. J Appl Physiol. 2009;106:1650–9. Scholar
  81. 81.
    Jerković R, Bosnar A, Jurisić-Erzen D, Azman J, Starcević-Klasan G, Peharec S, et al. The effects of long-term experimental diabetes mellitus type I on skeletal muscle regeneration capacity. Coll Antropol. 2009;33:1115–9.PubMedGoogle Scholar
  82. 82.
    Kim TN, Park MS, Yang SJ, Yoo HJ, Kang HJ, Song W, et al. Prevalence and determinant factors of sarcopenia in patients with type 2 diabetes: the Korean sarcopenic obesity study (KSOS). Diabetes Care. 2010;33:1497–9. Scholar
  83. 83.
    Umegaki H. Sarcopenia and diabetes: Hyperglycemia is a risk factor for age-associated muscle mass and functional reduction. J Diabetes Investig. 2015;6:623–4. Scholar
  84. 84.
    Macgilchrist C, Paul L, Ellis BM, Howe TE, Kennon B, Godwin J. Lower-limb risk factors for falls in people with diabetes mellitus. Diabet Med. 2010;27:162–8. Scholar
  85. 85.
    Palermo A, Strollo R, Maddaloni E, Tuccinardi D, D’Onofrio L, Briganti SI, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol. 2015;82(4):615–9. Scholar
  86. 86.
    Choi Y-K, Kim M-K, Bae KH, Seo H-A, Jeong J-Y, Lee W-K, et al. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract. 2013;100:96–101. Scholar
  87. 87.
    Kanazawa I, Yamaguchi T, Yano S, et al. Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun. 2008;375:414–9. Scholar
  88. 88.
    Jang WG, Kim EJ, Bae I-H, et al. Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2. Bone. 2011;48:885–93. Scholar
  89. 89.
    Zhen D, Chen Y, Tang X. Metformin reverses the deleterious effects of high glucose on osteoblast function. J Diabetes Complicat. 2010;24:334–44. Scholar
  90. 90.
    Molinuevo MS, Schurman L, McCarthy AD, et al. Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J Bone Miner Res. 2010;25:211–21. Scholar
  91. 91.
    Gao Y, Li Y, Xue J, et al. Effect of the anti-diabetic drug metformin on bone mass in ovariectomized rats. Eur J Pharmacol. 2010;635:231–6. Scholar
  92. 92.
    Sedlinsky C, Molinuevo MS, Cortizo AM, et al. Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats. Eur J Pharmacol. 2011;668:477–85. Scholar
  93. 93.
    Tolosa MJ, Chuguransky SR, Sedlinsky C, et al. Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: preventive effects of metformin. Diabetes Res Clin Pract. 2013;101:177–86. Scholar
  94. 94.
    Kasai T, Bandow K, Suzuki H, et al. Osteoblast differentiation is functionally associated with decreased AMP kinase activity. J Cell Physiol. 2009;221:740–9. Scholar
  95. 95.
    Salai M, Somjen D, Gigi R, et al. Effects of commonly used medications on bone tissue mineralisation in SaOS-2 human bone cell line: an in vitro study. Bone Joint J. 2013;95-B:1575–80. Scholar
  96. 96.
    Mai Q-G, Zhang Z-M, Xu S, et al. Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem. 2011;112:2902–9. Scholar
  97. 97.
    Liu L, Zhang C, Hu Y, Peng B. Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin. J Endod. 2012;38:943–7. Scholar
  98. 98.
    Wu W, Ye Z, Zhou Y, Tan W-S. AICAR, a small chemical molecule, primes osteogenic differentiation of adult mesenchymal stem cells. Int J Artif Organs. 2011;34:1128–36. Scholar
  99. 99.
    Patel JJ, Butters OR, Arnett TR. PPAR agonists stimulate adipogenesis at the expense of osteoblast differentiation while inhibiting osteoclast formation and activity. Cell Biochem Funct. 2014;32(4):368–77. Scholar
  100. 100.
    Jeyabalan J, Viollet B, Smitham P, et al. The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing. Osteoporos Int. 2013;24:2659–70. Scholar
  101. 101.
    Colhoun HM, Livingstone SJ, Looker HC, et al. Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs. Diabetologia. 2012;55:2929–37. Scholar
  102. 102.
    Napoli N, Strotmeyer ES, Ensrud KE, et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia. 2014;57:2057–65. Scholar
  103. 103.
    Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–43. Scholar
  104. 104.
    Kahn SE, Zinman B, Lachin JM, et al. Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care. 2008;31:845–51. Scholar
  105. 105.
    Monami M, Dicembrini I, Kundisova L, et al. A meta-analysis of the hypoglycemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes. Diabetes Obes Metab. 2014;16(9):833–40. Scholar
  106. 106.
    Johnston SS, Conner C, Aagren M, et al. Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab. 2012;14:634–43. Scholar
  107. 107.
    Dormuth CR, Carney G, Carleton B, et al. Thiazolidinediones and fractures in men and women. Arch Intern Med. 2009;169:1395–402. Scholar
  108. 108.
    Monami M, Cresci B, Colombini A, et al. Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care. 2008;31:199–203. Scholar
  109. 109.
    Michalik L, Auwerx J, Berger JP, et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev. 2006;58:726–41. Scholar
  110. 110.
    Ahmadian M, Suh JM, Hah N, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19:557–66. Scholar
  111. 111.
    Shockley KR, Lazarenko OP, Czernik PJ, et al. PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells. J Cell Biochem. 2009;106:232–46. Scholar
  112. 112.
    Johnson TE, Vogel R, Rutledge SJ, et al. Thiazolidinedione effects on glucocorticoid receptor-mediated gene transcription and differentiation in osteoblastic cells. Endocrinology. 1999;140:3245–54. Scholar
  113. 113.
    Gustafson B, Eliasson B, Smith U. Thiazolidinediones increase the wingless-type MMTV integration site family (WNT) inhibitor Dickkopf-1 in adipocytes: a link with osteogenesis. Diabetologia. 2010;53:536–40. Scholar
  114. 114.
    Mieczkowska A, Baslé MF, Chappard D, Mabilleau G. Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40-dependent mechanism. J Biol Chem. 2012;287:23517–26. Scholar
  115. 115.
    Mabilleau G, Mieczkowska A, Edmonds ME. Thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression. Diabet Med. 2010;27:925–32. Scholar
  116. 116.
    Yakar S, Courtland H-W, Clemmons D. IGF-1 and bone: new discoveries from mouse models. J Bone Miner Res. 2010;25:2543–52. Scholar
  117. 117.
    Lecka-Czernik B, Ackert-Bicknell C, Adamo ML, et al. Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by rosiglitazone suppresses components of the insulin-like growth factor regulatory system in vitro and in vivo. Endocrinology. 2007;148:903–11. Scholar
  118. 118.
    Wan Y, Chong L-W, Evans RM. PPAR-gamma regulates osteoclastogenesis in mice. Nat Med. 2007;13:1496–503. Scholar
  119. 119.
    Sottile V, Seuwen K, Kneissel M. Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int. 2004;75:329–37. Scholar
  120. 120.
    Syversen U, Stunes AK, Gustafsson BI, et al. Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord. 2009;9:10. Scholar
  121. 121.
    Krause U, Harris S, Green A, et al. Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells for improved osteoinductive therapy. Proc Natl Acad Sci U S A. 2010;107:4147–52. Scholar
  122. 122.
    Seto-Young D, Paliou M, Schlosser J, et al. Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J Clin Endocrinol Metab. 2005;90:6099–105. Scholar
  123. 123.
    Seto-Young D, Avtanski D, Parikh G, et al. Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase. Horm Metab Res. 2011;43:250–6. Scholar
  124. 124.
    Schwartz AV, Sellmeyer DE, Vittinghoff E, et al. Thiazolidinedione (TZD) use and bone loss in older diabetic adults. J Clin Endocrinol Metab. 2006;91:3349–54.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Solomon DH, Cadarette SM, Choudhry NK, et al. A cohort study of thiazolidinediones and fractures in older adults with diabetes. J Clin Endocrinol Metab. 2009;94:2792–8. Scholar
  126. 126.
    Kanazawa I, Yamaguchi T, Yamamoto M, Sugimoto T. Relationship between treatments with insulin and oral hypoglycemic agents versus the presence of vertebral fractures in type 2 diabetes mellitus. J Bone Miner Metab. 2010;28:554–60. Scholar
  127. 127.
    Habib ZA, Havstad SL, Wells K, et al. Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95:592–600. Scholar
  128. 128.
    Douglas IJ, Evans SJ, Pocock S, Smeeth L. The risk of fractures associated with thiazolidinediones: a self-controlled case-series study. PLoS Med. 2009;6:e1000154. Scholar
  129. 129.
    Meier C, Kraenzlin ME, Bodmer M, et al. Use of thiazolidinediones and fracture risk. Arch Intern Med. 2008;168:820–5. Scholar
  130. 130.
    Aubert RE, Herrera V, Chen W, et al. Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab. 2010;12:716–21. Scholar
  131. 131.
    Bilik D, McEwen LN, Brown MB, et al. Thiazolidinediones and fractures: evidence from translating research into action for diabetes. J Clin Endocrinol Metab. 2010;95:4560–5. Scholar
  132. 132.
    Hsiao F-Y, Mullins CD. The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case-control study. Diabetologia. 2010;53:489–96. Scholar
  133. 133.
    Bazelier MT, Vestergaard P, Gallagher AM, van Staa T-P, Cooper C, Leufkens HGM, et al. Risk of fracture with thiazolidinediones: disease or drugs? Calcif Tissue Int. 2012;90:450–7. Scholar
  134. 134.
    Jones SG, Momin SR, Good MW, et al. Distal upper and lower limb fractures associated with thiazolidinedione use. Am J Manag Care. 2009;15:491–6.PubMedGoogle Scholar
  135. 135.
    Zhu Z-N, Jiang Y-F, Ding T. Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone. 2014;68:115–23. Scholar
  136. 136.
    Grey A, Bolland M, Gamble G, et al. The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab. 2007;92:1305–10. Scholar
  137. 137.
    Harsløf T, Wamberg L, Møller L, et al. Rosiglitazone decreases bone mass and bone marrow fat. J Clin Endocrinol Metab. 2011;96:1541–8. Scholar
  138. 138.
    Berberoglu Z, Yazici AC, Demirag NG. Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study. Clin Endocrinol. 2010;73:305–12. Scholar
  139. 139.
    Yaturu S, Bryant B, Jain SK. Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care. 2007;30:1574–6. Scholar
  140. 140.
    Bilezikian JP, Josse RG, Eastell R, et al. Rosiglitazone decreases bone mineral density and increases bone turnover in postmenopausal women with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013;98:1519–28. Scholar
  141. 141.
    Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125–35. Scholar
  142. 142.
    Kanazawa I, Yamaguchi T, Yano S, et al. Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus. Osteoporos Int. 2010;21:2013–8. Scholar
  143. 143.
    Grey A, Bolland M, Fenwick S, et al. The skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial. Eur J Endocrinol. 2014;170:255–62. Scholar
  144. 144.
    Dormandy J, Bhattacharya M, van Troostenburg de Bruyn A-R. Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Drug Saf. 2009;32:187–202.CrossRefGoogle Scholar
  145. 145.
    Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696–705. Scholar
  146. 146.
    Pacheco-Pantoja EL, Ranganath LR, Gallagher JA, et al. Receptors and effects of gut hormones in three osteoblastic cell lines. BMC Physiol. 2011;11:12. Scholar
  147. 147.
    Kim J-Y, Lee S-K, Jo K-J, et al. Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. Life Sci. 2013;92:533–40. Scholar
  148. 148.
    Nuche-Berenguer B, Lozano D, Gutiérrez-Rojas I, et al. GLP-1 and exendin-4 can reverse hyperlipidic-related osteopenia. J Endocrinol. 2011;209:203–10. Scholar
  149. 149.
    Ma X, Meng J, Jia M, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats. J Bone Miner Res. 2013;28:1641–52. Scholar
  150. 150.
    Yamada C, Yamada Y, Tsukiyama K, et al. The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology. 2008;149:574–9. Scholar
  151. 151.
    Su B, Sheng H, Zhang M, et al. Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists’ treatment: a meta-analysis of randomized controlled trials. Endocrine. 2014;48(1):107–15. Scholar
  152. 152.
    Monami M, Dicembrini I, Antenore A, Mannucci E. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care. 2011;34:2474–6. Scholar
  153. 153.
    Bilezikian JP, Watts NB, Usiskin K, et al. Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J Clin Endocrinol Metab. 2016;101(1):44–51. Scholar
  154. 154.
    Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101(1):157–66. Scholar
  155. 155.
    Ljunggren Ö, Bolinder J, Johansson L, et al. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2012;14:990–9. Scholar
  156. 156.
    Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2013;16(2):159–69. Scholar
  157. 157.
    Pater A, Sypniewska G, Pilecki O. Biochemical markers of bone cell activity in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2010;23:81–6.CrossRefPubMedGoogle Scholar
  158. 158.
    Karagüzel G, Akçurin S, Ozdem S, Boz A, Bircan I. Bone mineral density and alterations of bone metabolism in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2006;19:805–14.PubMedGoogle Scholar
  159. 159.
    Alexopoulou O, Jamart J, Devogelaer JP, Brichard S, de Nayer PBM. Bone density and markers of bone remodeling in type 1 male diabetic patients. Diabetes Metab. 2006;32:453–8.CrossRefPubMedGoogle Scholar
  160. 160.
    Lumachi F, Camozzi V, Tombolan V, Luisetto G. Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus. Ann N Y Acad Sci. 2009;1173:E64–7. Scholar
  161. 161.
    Jehle PM, Jehle DR, Mohan S, Böhm BO. Serum levels of insulin-like growth factor system components and relationship to bone metabolism in Type 1 and Type 2 diabetes mellitus patients. J Endocrinol. 1998;159:297–306.CrossRefPubMedGoogle Scholar
  162. 162.
    Starup-Linde J, Vestergaard P, Vestergaard P, Giangregorio LM, Leslie WD, Lix LM, et al. Biochemical bone turnover markers in diabetes mellitus — a systematic review. Bone. 2015;82:69–78. Scholar
  163. 163.
    Gaudio A, Privitera F, Battaglia K, Torrisi V, Sidoti MH, Pulvirenti I, 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. Scholar
  164. 164.
    Catalano A, Pintaudi B, Morabito N, Di Vieste G, Giunta L, Bruno ML, et al. Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus. Eur J Endocrinol. 2014;171:293–300. Scholar
  165. 165.
    Register TC, Hruska KA, Divers J, Bowden DW, Palmer ND, Carr JJ, et al. Sclerostin is positively associated with bone mineral density in men and women and negatively associated with carotid calcified atherosclerotic plaque in men from the African American-diabetes heart study. J Clin Endocrinol Metab. 2014;99:315–21. Scholar
  166. 166.
    Kanazawa I, Yamaguchi T, Sugimoto T. Serum insulin-like growth factor-I is a marker for assessing the severity of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Osteoporos Int. 2011;22:1191–8. Scholar
  167. 167.
    Yamamoto M, Yamauchi M, Sugimoto T. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013;98:4030–7. Scholar
  168. 168.
    Jiajue R, Jiang Y, Wang O, Li M, Xing X, Cui L, et al. Suppressed bone turnover was associated with increased osteoporotic fracture risks in non-obese postmenopausal Chinese women with type 2 diabetes mellitus. Osteoporos Int. 2014;25:1999–2005. Scholar
  169. 169.
    Starup-Linde J, Eriksen SA, Lykkeboe S, Handberg A, Vestergaard P. Biochemical markers of bone turnover in diabetes patients--a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int. 2014;25:1697–708. Scholar
  170. 170.
    Hampson G, Evans C, Petitt RJ, Evans WD, Woodhead SJ, Peters JR, et al. Bone mineral density, collagen type 1 alpha 1 genotypes and bone turnover in premenopausal women with diabetes mellitus. Diabetologia. 1998;41:1314–20.CrossRefPubMedGoogle Scholar
  171. 171.
    Eller-Vainicher C, Zhukouskaya VV, Tolkachev YV, Koritko SS, Cairoli E, Grossi E, et al. Low bone mineral density and its predictors in type 1 diabetic patients evaluated by the classic statistics and artificial neural network analysis. Diabetes Care. 2011;34:2186–91. Scholar
  172. 172.
    Joshi A, Varthakavi P, Chadha M, Bhagwat N. A study of bone mineral density and its determinants in type 1 diabetes mellitus. J Osteoporos. 2013;2013:397814. Scholar
  173. 173.
    Bridges MJ, Moochhala SH, Barbour J, Kelly CA. Influence of diabetes on peripheral bone mineral density in men: a controlled study. Acta Diabetol. 2005;42:82–6. Scholar
  174. 174.
    Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res. 2007;22:1317–28. Scholar
  175. 175.
    Bechtold S, Putzker S, Bonfig W, Fuchs O, Dirlenbach I, Schwarz HP. Bone size normalizes with age in children and adolescents with type 1 diabetes. Diabetes Care. 2007;30:2046–50. Scholar
  176. 176.
    Mastrandrea LD, Wactawski-Wende J, Donahue RP, Hovey KM, Clark A, Quattrin T. Young women with type 1 diabetes have lower bone mineral density that persists over time. Diabetes Care. 2008;31:1729–35. Scholar
  177. 177.
    Sellmeyer DE, Civitelli R, Hofbauer LC, Khosla S, Lecka-Czernik B, Schwartz AV. Skeletal metabolism, fracture risk, and fracture outcomes in type 1 and type 2 diabetes. Diabetes. 2016;65:1757–66. Scholar
  178. 178.
    Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z, 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. Scholar
  179. 179.
    Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Zmuda JM, et al. Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: the health, aging, and body composition study. J Bone Miner Res. 2004;19:1084–91. Scholar
  180. 180.
    Shan PF, Wu XP, Zhang H, Cao XZ, Yuan LQ, Liao EY. Age-related bone mineral density, osteoporosis rate and risk of vertebral fracture in mainland Chinese women with type 2 diabetes mellitus. J Endocrinol Investig. 2011;34:190–6. Scholar
  181. 181.
    Schwartz AV, Ewing SK, Porzig AM, McCulloch CE, Resnick HE, Hillier TA, et al. Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol (Lausanne). 2013;4:62. Scholar
  182. 182.
    Keegan THM, Schwartz AV, Bauer DC, Sellmeyer DE, Kelsey JL, Fracture Intervention Trial. Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women: the fracture intervention trial. Diabetes Care. 2004;27:1547–53.CrossRefPubMedGoogle Scholar
  183. 183.
    Khalil N, Sutton-Tyrrell K, Strotmeyer ES, Greendale GA, Vuga M, Selzer F, et al. Menopausal bone changes and incident fractures in diabetic women: a cohort study. Osteoporos Int. 2011;22:1367–76. Scholar
  184. 184.
    Schwartz AV, Sellmeyer DE, Strotmeyer ES, Tylavsky FA, Feingold KR, Resnick HE, et al. Diabetes and bone loss at the hip in older black and white adults. J Bone Miner Res. 2005;20:596–603. Scholar
  185. 185.
    Abdalrahaman N, McComb C, Foster JE, McLean J, Lindsay RS, McClure J, et al. Deficits in trabecular bone microarchitecture in young women with type 1 diabetes mellitus. J Bone Miner Res. 2015;30:1386–93. Scholar
  186. 186.
    Shanbhogue VV, Hansen S, Frost M, Jørgensen NR, Hermann AP, Henriksen JE, et al. Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with type 1 diabetes mellitus. J Bone Miner Res. 2015;30:2188–99. Scholar
  187. 187.
    Burghardt AJ, Issever AS, Schwartz AV, Davis KA, Masharani U, Majumdar S, 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. Scholar
  188. 188.
    Yu EW, Putman MS, Derrico N, Abrishamanian-Garcia G, Finkelstein JS, Bouxsein ML. Defects in cortical microarchitecture among African-American women with type 2 diabetes. Osteoporos Int. 2015;26:673–9. Scholar
  189. 189.
    Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res. 2013;28:313–24. Scholar
  190. 190.
    Farr JN, Drake MT, Amin S, Melton LJ, McCready LK, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res. 2014;29:787–95. Scholar
  191. 191.
    Dhaliwal R, Cibula D, Ghosh C, Weinstock RS, Moses AM. Bone quality assessment in type 2 diabetes mellitus. Osteoporos Int. 2014;25(7):1969–73. Scholar
  192. 192.
    Kim JH, Choi HJ, Ku EJ, Kim KM, Kim SW, Cho NH, et al. Trabecular bone score as an indicator for skeletal deterioration in diabetes. J Clin Endocrinol Metab. 2015;100(2):475–82. Scholar
  193. 193.
    Leslie WD, Aubry-Rozier B, Lamy O, Hans D, Manitoba Bone Density Program. TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab. 2013;98:602–9. Scholar
  194. 194.
    Neumann T, Lodes S, Kästner B, Lehmann T, Hans D, Lamy O, et al. Trabecular bone score in type 1 diabetes--a cross-sectional study. Osteoporos Int. 2016;27:127–33. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Andrea Palermo
    • 1
  • Anda Mihaela Naciu
    • 1
  • Gaia Tabacco
    • 1
  • Luca D’Onofrio
    • 2
  • Nicola Napoli
    • 1
  1. 1.Unit of Endocrinology and DiabetesCampus Bio-Medico UniversityRomeItaly
  2. 2.Department of Experimental Medicine“Sapienza” University of RomeRomeItaly

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