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Current Osteoporosis Reports

Published in:

01-10-2019 | Type 2 Diabetes | Biomechanics (G Niebur and J Wallace, Section editors)

The Effect of Type 2 Diabetes on Bone Biomechanics

Authors: Lamya Karim, Taraneh Rezaee, Rachana Vaidya

Published in: Current Osteoporosis Reports | Issue 5/2019

Abstract

Purpose of Review

There is ample evidence that patients with type 2 diabetes (T2D) have increased risk of fracture even though they have normal or high bone mineral density. As a result, poor bone quality is suggested to contribute to skeletal fragility in this population. Thus, our goal was to conduct a comprehensive literature review to understand how bone quality components are altered in T2D and their effects on bone biomechanics and fracture risk.

Recent Findings

T2D does affect bone quality via alterations in bone microarchitecture, organic matrix, and cellular behavior. Further, studies indicate that bone biomechanical properties are generally deteriorated in T2D, but there are few reports in patients.

Summary

Additional work is needed to better understand molecular and cellular mechanisms that contribute to skeletal fragility in T2D. This knowledge can contribute to the development of improved diagnostic tools and drug targets to for improved quality of life for those with T2D.

McCabe L, Zhang J, Raehtz S. Understanding the skeletal pathology of type 1 and 2 diabetes mellitus. Crit Rev Eukaryot Gene Expr. 2011;21(2):187–206.CrossRef

Nicodemus KK, Folsom AR. Iowa Women's health S. type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care. 2001;24(7):1192–7.CrossRef

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(9):3404–10. https://doi.org/10.1210/jc.2006-0614.CrossRefPubMed

Melton LJ 3rd, 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(8):1334–42. https://doi.org/10.1359/jbmr.080323.CrossRefPubMedPubMedCentral

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. Arch Intern Med. 2005;165(14):1612–7. https://doi.org/10.1001/archinte.165.14.1612.CrossRefPubMed

Moseley KF. Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes. 2012;19(2):128–135. https://doi.org/10.1097/MED.0b013e328350a6e1.CrossRef

Ryan, TM. Biomechanics/mechanobiology. 2018, The International Encyclopedia of Biological Anthropology, https://doi.org/10.1002/9781118584538.ieba0057.

Burr DB. Allen MR. Basic and applied bone biology: Academic Press; 2019.

Karim L, Van Vliet M, Bouxsein ML. Comparison of cyclic and impact-based reference point indentation measurements in human cadaveric tibia. Bone. 2015;in press. 2018 ;106:90–95. https://doi.org/10.1016/j.bone.2015.03.021.CrossRef

10.

• Farr JN, Drake MT, Amin S, Melton LJ 3rd, LK MC, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res Off J Am Soc Bone Miner Res. 2014;29(4):787–95. https://doi.org/10.1002/jbmr.2106 This study is one of 4 studies that have directly assessed biomechanical properties in bone from type 2 diabetic patients. This study shows there is deteriorated bone material strength indexed as assessed by impact-based reference point indentation in type 2 diabetic patients compared to non-diabetics. CrossRef

11.

Acevedo C, Sylvia M, Schaible E, Graham JL, Stanhope KL, Metz LN, et al. Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2. Diabetes. 2018;33(6):1066–75.

12.

Reinwald S, Peterson RG, Allen MR, Burr DB. Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. Am J Physiol Endocrinol Metab. 2009;296(4):E765–74. https://doi.org/10.1152/ajpendo.90937.2008.CrossRefPubMedPubMedCentral

13.

Mathey J, Horcajada-Molteni MN, Chanteranne B, Picherit C, Puel C, Lebecque P, et al. Bone mass in obese diabetic Zucker rats: influence of treadmill running. Calcif Tissue Int. 2002;70(4):305–11. https://doi.org/10.1007/s00223-001-2077-8.CrossRefPubMed

14.

Hamann C, Rauner M, Hohna Y, Bernhardt R, Mettelsiefen J, Goettsch C, et al. Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus. J Bone Miner Res. 2013;28(3):627–38. https://doi.org/10.1002/jbmr.1803.CrossRefPubMed

15.

Gallant MA, Brown DM, Organ JM, Allen MR, Burr DB. Reference-point indentation correlates with bone toughness assessed using whole-bone traditional mechanical testing. Bone. 2013;53(1):301–5. https://doi.org/10.1016/j.bone.2012.12.015.CrossRefPubMed

16.

Acevedo C, Sylvia M, Schaible E, Graham JL, Stanhope KL, Metz LN, et al. Contributions of material properties and structure to increased bone fragility for a given bone mass in the UCD-T2DM rat model of type 2 diabetes. J Bone Miner Res Off J Am Soc Bone Miner Res. 2018;33:1066–75. https://doi.org/10.1002/jbmr.3393.CrossRef

17.

• Karim L, Moulton J, Van Vliet M, Velie K, Robbins A, Malekipour F, et al. Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes. Bone. 2018;114:32–9. https://doi.org/10.1016/j.bone.2018.05.030 This study is one of 4 studies that have directly assessed biomechanical properties in bone from type 2 diabetic patients. This study shows there is deteriorated indentation properties in cortical bone as assessed by cyclic-based reference point indentation as well as increased advanced glycation end-products, but no major differences in trabecular bone mechanical properties in type 2 diabetic patients compared to non-diabetics. CrossRefPubMedPubMedCentral

18.

• Hunt H, Torres A, Palomino P, Marty E, Saiyed R, Cohn M, et al. Altered tissue composition, microarchitecture, and mechanical performance in cancellous bone from men with type 2 diabetes mellitus. J Bone Miner Res. 2019. https://doi.org/10.1002/jbmr.3711 This study is one of 4 studies that have directly assessed biomechanical properties in bone from type 2 diabetic patients. This study shows increaesd mineral content is related to increased trabecular bone strength, while increased advanced glycation end-products are related to deteriorated postyield strain and toughness in trabecualr bone of type 2 diabetics compared to non-diabetics. CrossRef

19.

• Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, Mc Mahon DJ, et al. Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes. J Clin Endocrinol Metab. 2016;101(6):2502–10. https://doi.org/10.1210/jc.2016-1437 This study is one of 4 studies that have directly assessed biomechanical properties in bone from type 2 diabetic patients. This study shows decreased bone material strength index assessed by impact-based reference point indentation in type 2 diabetics compared to non-diabetics. CrossRefPubMedPubMedCentral

20.

Vashishth D, Gibson GJ, Khoury JI, Schaffler MB, Kimura J, Fyhrie DP. Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone. 2001;28(2):195–201.CrossRef

21.

Tang SY, Zeenath U, Vashishth D. Effects of non-enzymatic glycation on cancellous bone fragility. Bone. 2007;40(4):1144–51. https://doi.org/10.1016/j.bone.2006.12.056.CrossRefPubMed

22.

Sroga GE, Siddula A, Vashishth D. Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose. PLoS One. 2015;10(2):e0117240. https://doi.org/10.1371/journal.pone.0117240.CrossRefPubMedPubMedCentral

23.

Abar O, Dharmar S, Tang SY. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res. 2018;7(1):105–10. https://doi.org/10.1302/2046-3758.71.BJR-2017-0135.R1.CrossRefPubMedPubMedCentral

24.

Zeitoun D, Caliaperoumal G, Bensidhoum M, Constans JM, Anagnostou F, Bousson V. Microcomputed tomography of the femur of diabetic rats: alterations of trabecular and cortical bone microarchitecture and vasculature-a feasibility study. Eur Radiol Exp. 2019;3(1):17. https://doi.org/10.1186/s41747-019-0094-5.CrossRefPubMedPubMedCentral

25.

Dirkes RK, Ortinau LC, Richard MW, Linden MA, Rector RS, Hinton PS. Bone Geometry and Trabecular and Cortical Microarchitecture are Altered by Type 2 Diabetes, but not Insulin Resistance, in the Hyperphagic OLETF Rat. The FASEB J. 2016;30(1_supplement):lb263-lb. https://doi.org/10.1096/fasebj.30.1_supplement.lb263.CrossRef

26.

Paccou J, Ward KA, Jameson KA, Dennison EM, Cooper C, Edwards MH. Bone microarchitecture in men and women with diabetes: the importance of cortical porosity. Calcif Tissue Int. 2016;98(5):465–73. https://doi.org/10.1007/s00223-015-0100-8.CrossRefPubMed

27.

Samelson EJ, Demissie S, Cupples LA, Zhang X, Xu H, Liu CT, et al. Diabetes and deficits in cortical bone density, microarchitecture, and bone size: Framingham HR-pQCT study. J Bone Miner Res. 2018;33(1):54–62. https://doi.org/10.1002/jbmr.3240.CrossRefPubMed

28.

de Waard EAC, de Jong JJA, Koster A, Savelberg H, van Geel TA, Houben A, et al. The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study. Osteoporos Int. 2018;29(12):2725–38. https://doi.org/10.1007/s00198-018-4678-3.CrossRefPubMedPubMedCentral

29.

Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354(21):2250–61. https://doi.org/10.1056/NEJMra053077.CrossRefPubMed

30.

Bailey AJ, Paul RG, Knott L. Mechanisms of maturation and ageing of collagen. Mech Ageing Dev. 1998;106(1–2):1–56 doi:S0047-6374(98)00119-5 [pii].CrossRef

31.

Knott L, Bailey AJ. Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. Bone. 1998;22(3):181–7 doi:S8756328297002792 [pii].CrossRef

32.

Tang SY, Vashishth D. Non-enzymatic glycation alters microdamage formation in human cancellous bone. Bone. 2010;46(1):148–54. https://doi.org/10.1016/j.bone.2009.09.003.CrossRefPubMed

33.

Zioupos P. Accumulation of in-vivo fatigue microdamage and its relation to biomechanical properties in ageing human cortical bone. J Microsc. 2001;201:270–8.CrossRef

34.

Norman TL, Yeni YN, Brown CU, Wang Z. Influence of microdamage on fracture toughness of the human femur and tibia. Bone. 1998;23(3):303–6.CrossRef

35.

Vashishth D. Advanced glycation end-products and bone fractures. IBMS Bonekey. 2009;6(8):268–78. https://doi.org/10.1138/20090390.CrossRefPubMedPubMedCentral

36.

Karim L, Tang SY, Sroga GE, Vashishth D. Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2013;24(9):2441–7. https://doi.org/10.1007/s00198-013-2319-4.CrossRef

37.

Hernandez CJ, Tang SY, Baumbach BM, Hwu PB, Sakkee AN, van der Ham F, et al. Trabecular microfracture and the influence of pyridinium and non-enzymatic glycation-mediated collagen cross-links. Bone. 2005;37(6):825–32. https://doi.org/10.1016/j.bone.2005.07.019.CrossRefPubMedPubMedCentral

38.

Ahmed N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67(1):3–21. https://doi.org/10.1016/j.diabres.2004.09.004.CrossRefPubMed

39.

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(10):1514–23.CrossRef

40.

Devlin MJ, Van Vliet M, Motyl K, Karim L, Brooks DJ, Louis L, et al. Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse. Endocrinology. 2014;155(10):3806–16. https://doi.org/10.1210/en.2014-1041.CrossRefPubMedPubMedCentral

41.

Poundarik AA, Wu PC, Evis Z, Sroga GE, Ural A, Rubin M, et al. A direct role of collagen glycation in bone fracture. J Mech Behav Biomed Mater. 2015;52:120–30. https://doi.org/10.1016/j.jmbbm.2015.08.012.CrossRefPubMedPubMedCentral

42.

Hunt HB, Pearl JC, Diaz DR, King KB, Donnelly E. Bone tissue collagen maturity and mineral content increase with sustained hyperglycemia in the KK-ay murine model of type 2 diabetes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018;33(5):921–9. https://doi.org/10.1002/jbmr.3365.CrossRef

43.

Fajardo RJ, Karim L, Calley VI, Bouxsein ML. A review of rodent models of type 2 diabetic skeletal fragility. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;29(5):1025–40. https://doi.org/10.1002/jbmr.2210.CrossRef

44.

Nyman JS, Roy A, Tyler JH, Acuna RL, Gayle HJ, Wang X. Age-related factors affecting the postyield energy dissipation of human cortical bone. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2007;25(5):646–55. https://doi.org/10.1002/jor.20337.CrossRef

45.

Wang X, Shen X, Li X, Agrawal CM. Age-related changes in the collagen network and toughness of bone. Bone. 2002;31(1):1–7.CrossRef

46.

Nyman JS, Roy A, Acuna RL, Gayle HJ, Reyes MJ, Tyler JH, et al. Age-related effect on the concentration of collagen crosslinks in human osteonal and interstitial bone tissue. Bone. 2006;39(6):1210–7. https://doi.org/10.1016/j.bone.2006.06.026.CrossRefPubMedPubMedCentral

47.

Viguet-Carrin S, Farlay D, Bala Y, Munoz F, Bouxsein ML, Delmas PD. An in vitro model to test the contribution of advanced glycation end products to bone biomechanical properties. Bone. 2008;42(1):139–49. https://doi.org/10.1016/j.bone.2007.08.046.CrossRefPubMed

48.

Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D. Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int. 2009;20(6):887–94. https://doi.org/10.1007/s00198-008-0754-4.CrossRefPubMed

49.

Reddy GK. Glucose-mediated in vitro glycation modulates biomechanical integrity of the soft tissues but not hard tissues. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2003;21(4):738–43. https://doi.org/10.1016/S0736-0266(03)00006-8.CrossRef

50.

Gauthier R, Follet H, Langer M, Gineyts E, Rongiéras F. Peyrin F et al. Relationships between human cortical bone toughness and collagen cross-links on paired anatomical locations. 2018;112:202–11.

51.

Willett TL, Dapaah DY, Uppuganti S, Granke M, Nyman JS. Bone collagen network integrity and transverse fracture toughness of human cortical bone. Bone. 2019;120:187–93. https://doi.org/10.1016/j.bone.2018.10.024.CrossRefPubMed

52.

Purnamasari D, Puspitasari MD, Setiyohadi B, Nugroho P, Isbagio H. Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study. BMC Endocr Disord. 2017;17(1):72. https://doi.org/10.1186/s12902-017-0224-0.CrossRefPubMedPubMedCentral

53.

Sassi F, Buondonno I, Luppi C, Spertino E, Stratta E, Di Stefano M, et al. Type 2 diabetes affects bone cells precursors and bone turnover. BMC Endocr Disord. 2018;18(1):55. https://doi.org/10.1186/s12902-018-0283-x.CrossRefPubMedPubMedCentral

54.

Tanaka H, Yamashita T, Yoneda M, Takagi S, Miura T. Characteristics of bone strength and metabolism in type 2 diabetic model Tsumura, Suzuki. Obese Diabetes mice Bone reports. 2018;9:74–83. https://doi.org/10.1016/j.bonr.2018.07.004.CrossRefPubMed

55.

Levinger I, Seeman E, Jerums G, McConell GK, Rybchyn MS, Cassar S, et al. Glucose-loading reduces bone remodeling in women and osteoblast function in vitro. Physiol Rep. 2016;4(3). https://doi.org/10.14814/phy2.12700.CrossRef

56.

Mabilleau G, Perrot R, Flatt PR, Irwin N, Chappard D. High fat-fed diabetic mice present with profound alterations of the osteocyte network. Bone. 2016;90:99–106. https://doi.org/10.1016/j.bone.2016.06.008.CrossRefPubMed

57.

Pereira M, Gohin S, Lund N, Hvid A, Smitham PJ, Oddy MJ, et al. Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus. Osteoporos Int. 2017;28(1):309–20. https://doi.org/10.1007/s00198-016-3718-0.CrossRefPubMed

58.

Plotkin LI, Gortazar AR, Davis HM, Condon KW, Gabilondo H, Maycas M, et al. Inhibition of osteocyte apoptosis prevents the increase in osteocytic receptor activator of nuclear factor kappaB ligand (RANKL) but does not stop bone resorption or the loss of bone induced by unloading. J Biol Chem. 2015;290(31):18934–42. https://doi.org/10.1074/jbc.M115.642090.CrossRefPubMedPubMedCentral

59.

Villasenor A, Aedo-Martin D, Obeso D, Erjavec I, Rodriguez-Coira J, Buendia I, et al. Metabolomics reveals citric acid secretion in mechanically-stimulated osteocytes is inhibited by high glucose. Sci Rep. 2019;9(1):2295. https://doi.org/10.1038/s41598-018-38154-6.CrossRefPubMedPubMedCentral

60.

Sun M, Yang J, Wang J, Hao T, Jiang D, Bao G, et al. TNF-alpha is upregulated in T2DM patients with fracture and promotes the apoptosis of osteoblast cells in vitro in the presence of high glucose. Cytokine. 2016;80:35–42. https://doi.org/10.1016/j.cyto.2016.01.011.CrossRefPubMed

61.

Liu C, Jiang D. High glucose-induced LIF suppresses osteoblast differentiation via regulating STAT3/SOCS3 signaling. Cytokine. 2017;91:132–9. https://doi.org/10.1016/j.cyto.2016.12.016.CrossRefPubMed

62.

Bierhaus A, Humpert PM, Stern DM, Arnold B, Nawroth PP. Advanced glycation end product receptor-mediated cellular dysfunction. Ann N Y Acad Sci. 2005;1043:676–80. https://doi.org/10.1196/annals.1333.077.CrossRefPubMed

63.

Phimphilai M, Pothacharoen P, Kongtawelert P, Chattipakorn N. Impaired osteogenic differentiation and enhanced cellular receptor of advanced glycation end products sensitivity in patients with type 2 diabetes. J Bone Miner Metab. 2017;35(6):631–41. https://doi.org/10.1007/s00774-016-0800-9.CrossRefPubMed

64.

Meng HZ, Zhang WL, Liu F, Yang MW. Advanced glycation end products affect osteoblast proliferation and function by modulating autophagy via the receptor of advanced glycation end products/Raf protein/mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase (RAGE/Raf/MEK/ERK) pathway. J Biol Chem. 2015;290(47):28189–99. https://doi.org/10.1074/jbc.M115.669499.CrossRefPubMedPubMedCentral

65.

Tanaka T, Takei Y, Zaima N, Moriyama T, Yamanouchi D. Hyperglycemia suppresses RANKL-induced osteoclast differentiation through LXRbeta expression in RAW264.7 cells. J Nutr Sci Vitaminol. 2017;63(1):28–34. https://doi.org/10.3177/jnsv.63.28.CrossRefPubMed

66.

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(6):853–62. https://doi.org/10.1002/jbmr.5650040610.CrossRefPubMed

67.

Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142(2):296–308. https://doi.org/10.1016/j.cell.2010.06.003.CrossRefPubMedPubMedCentral

68.

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(2):309–19. https://doi.org/10.1016/j.cell.2010.06.002.CrossRefPubMedPubMedCentral

69.

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(7):1292–9. https://doi.org/10.1007/s00125-005-1786-3.CrossRefPubMed

70.

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(5):554–60. https://doi.org/10.1007/s00774-010-0160-9.CrossRefPubMed

71.

Molinuevo MS, Schurman L, McCarthy AD, Cortizo AM, Tolosa MJ, Gangoiti MV, et al. Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J Bone Miner Res. 2010;25(2):211–21. https://doi.org/10.1359/jbmr.090732.CrossRefPubMed

72.

Meier C, Schwartz AV, Egger A, Lecka-Czernik B. Effects of diabetes drugs on the skeleton. Bone. 2016;82:93–100. https://doi.org/10.1016/j.bone.2015.04.026.CrossRefPubMed

73.

Mai QG, Zhang ZM, Xu S, Lu M, Zhou RP, Zhao L, et al. Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem. 2011;112(10):2902–9. https://doi.org/10.1002/jcb.23206.CrossRefPubMed

74.

Jeyabalan J, Viollet B, Smitham P, Ellis SA, Zaman G, Bardin C, et al. The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing. Osteoporos Int. 2013;24(10):2659–70. https://doi.org/10.1007/s00198-013-2371-0.CrossRefPubMedPubMedCentral

75.

Napoli N, Strotmeyer ES, Ensrud KE, Sellmeyer DE, Bauer DC, Hoffman AR, et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia. 2014;57(10):2057–65. https://doi.org/10.1007/s00125-014-3289-6.CrossRefPubMedPubMedCentral

76.

Chen HH, Horng MH, Yeh SY, Lin IC, Yeh CJ, Muo CH, et al. Glycemic control with thiazolidinedione is associated with fracture of T2DM patients. PLoS One. 2015;10(8):e0135530. https://doi.org/10.1371/journal.pone.0135530.CrossRefPubMedPubMedCentral

77.

Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2009;180(1):32–9. https://doi.org/10.1503/cmaj.080486.CrossRefPubMed

78.

Zhu ZN, Jiang YF, Ding T. Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone. 2014;68:115–23. https://doi.org/10.1016/j.bone.2014.08.010.CrossRefPubMed

79.

Schwartz AV, Chen H, Ambrosius WT, Sood A, Josse RG, Bonds DE, et al. Effects of TZD use and discontinuation on fracture rates in ACCORD bone study. J Clin Endocrinol Metab. 2015;100(11):4059–66. https://doi.org/10.1210/jc.2015-1215.CrossRefPubMedPubMedCentral

80.

Kahn SE, Zinman B, Lachin JM, Haffner SM, Herman WH, Holman RR, et al. Rosiglitazone-associated fractures in type 2 diabetes: an analysis from a diabetes outcome progression trial (ADOPT). Diabetes Care. 2008;31(5):845–51. https://doi.org/10.2337/dc07-2270.CrossRefPubMed

81.

Consoli A, Formoso G. Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus? Diabetes Obes Metab. 2013;15(11):967–77. https://doi.org/10.1111/dom.12101.CrossRefPubMed

82.

Pereira M, Jeyabalan J, Jorgensen CS, Hopkinson M, Al-Jazzar A, Roux JP, et al. Chronic administration of glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice. Bone. 2015;81:459–67. https://doi.org/10.1016/j.bone.2015.08.006.CrossRefPubMed

83.

Ma X, Meng J, Jia M, Bi L, Zhou Y, Wang Y, 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. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2013;28(7):1641–52. https://doi.org/10.1002/jbmr.1898.CrossRef

84.

Tsukiyama K, Yamada Y, Yamada C, Harada N, Kawasaki Y, Ogura M, et al. Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Molecular endocrinology (Baltimore, Md). 2006;20(7):1644–51. https://doi.org/10.1210/me.2005-0187.CrossRef

85.

Cheng L, Hu Y, Li YY, Cao X, Bai N, Lu TT, et al. Glucagon-like peptide-1 receptor agonists and risk of bone fracture in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes/metabolism research and reviews. 2019:e3168. https://doi.org/10.1002/dmrr.3168.

86.

Hinnen D, Nielsen LL, Waninger A, Kushner P. Incretin mimetics and DPP-IV inhibitors: new paradigms for the treatment of type 2 diabetes. Journal of the American Board of Family Medicine : JABFM. 2006;19(6):612–20.CrossRef

87.

Driessen JH, Henry RM, van Onzenoort HA, Lalmohamed A, Burden AM, Prieto-Alhambra D, et al. Bone fracture risk is not associated with the use of glucagon-like peptide-1 receptor agonists: a population-based cohort analysis. Calcif Tissue Int. 2015;97(2):104–12. https://doi.org/10.1007/s00223-015-9993-5.CrossRefPubMedPubMedCentral

88.

Driessen JH, van Onzenoort HA, Starup-Linde J, Henry R, Burden AM, Neef C, et al. Use of glucagon-like-peptide 1 receptor agonists and risk of fracture as compared to use of other anti-hyperglycemic drugs. Calcif Tissue Int. 2015;97(5):506–15. https://doi.org/10.1007/s00223-015-0037-y.CrossRefPubMedPubMedCentral

89.

Driessen JH, van Onzenoort HA, Starup-Linde J, Henry R, Neef C, van den Bergh J, et al. Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs. Pharmacoepidemiol Drug Saf. 2015;24(10):1017–25. https://doi.org/10.1002/pds.3837.CrossRefPubMed

90.

Mabilleau G, Mieczkowska A, Chappard D. Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials. J Diabetes. 2014;6(3):260–6. https://doi.org/10.1111/1753-0407.12102.CrossRefPubMed

91.

Mosenzon O, Wei C, Davidson J, Scirica BM, Yanuv I, Rozenberg A, et al. Incidence of fractures in patients with type 2 diabetes in the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38(11):2142–50. https://doi.org/10.2337/dc15-1068.CrossRefPubMed

92.

Mamza J, Marlin C, Wang C, Chokkalingam K, Idris I. DPP-4 inhibitor therapy and bone fractures in people with type 2 diabetes - a systematic review and meta-analysis. Diabetes Res Clin Pract. 2016;116:288–98. https://doi.org/10.1016/j.diabres.2016.04.029.CrossRefPubMed

93.

Wang C, Xiao F, Qu X, Zhai Z, Hu G, Chen X, et al. Sitagliptin, An Anti-diabetic Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis In Vivo and Inhibits RANKL-Induced Osteoclast Formation and Bone Resorption In Vitro. Front Pharmacol. 2017;8:407. https://doi.org/10.3389/fphar.2017.00407.CrossRefPubMedPubMedCentral

94.

Dombrowski S, Kostev K, Jacob L. Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients with type 2 diabetes in Germany-a retrospective analysis of real-world data. Osteoporos Int. 2017;28(8):2421–8. https://doi.org/10.1007/s00198-017-4051-y.CrossRefPubMed

95.

Choi HJ, Park C, Lee YK, Ha YC, Jang S, Shin CS. Risk of fractures and diabetes medications: a nationwide cohort study. Osteoporos Int. 2016;27(9):2709–15. https://doi.org/10.1007/s00198-016-3595-6.CrossRefPubMed

96.

Gamble JM, Donnan JR, Chibrikov E, Twells LK, Midodzi WK, Majumdar SR. The risk of fragility fractures in new users of dipeptidyl peptidase-4 inhibitors compared to sulfonylureas and other anti-diabetic drugs: a cohort study. Diabetes Res Clin Pract. 2018;136:159–67. https://doi.org/10.1016/j.diabres.2017.12.008.CrossRefPubMed

97.

Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD. Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin. Nutr Diabetes. 2014;4:e143. https://doi.org/10.1038/nutd.2014.40.CrossRefPubMedPubMedCentral

98.

Thrailkill KM, Clay Bunn R, Nyman JS, Rettiganti MR, Cockrell GE, Wahl EC, et al. SGLT2 inhibitor therapy improves blood glucose but does not prevent diabetic bone disease in diabetic DBA/2J male mice. Bone. 2016;82:101–7. https://doi.org/10.1016/j.bone.2015.07.025.CrossRefPubMed

99.

Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, et al. Effects of Canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101(1):157–66. https://doi.org/10.1210/jc.2015-3167.CrossRefPubMed

100.

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57. https://doi.org/10.1056/NEJMoa1611925.CrossRef

101.

Tang HL, Li DD, Zhang JJ, Hsu YH, Wang TS, Zhai SD, et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2016;18(12):1199–206. https://doi.org/10.1111/dom.12742.CrossRefPubMed

102.

Ruanpeng D, Ungprasert P, Sangtian J, Harindhanavudhi T. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis. Diabetes/metab Res Rev. 2017;33(6). https://doi.org/10.1002/dmrr.2903.CrossRef

103.

Li X, Li T, Cheng Y, Lu Y, Xue M, Xu L, et al. Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes mellitus: an updated meta-analysis. Diabetes/metabolism Res Rev. 2019:e3170. https://doi.org/10.1002/dmrr.3170.

Title: The Effect of Type 2 Diabetes on Bone Biomechanics
Authors: Lamya Karim
Taraneh Rezaee
Rachana Vaidya
Publication date: 01-10-2019
Publisher: Springer US
Keyword: Type 2 Diabetes
Published in: Current Osteoporosis Reports / Issue 5/2019
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-019-00526-w

At a glance: The STEP trials

Springer Medicine

The Effect of Type 2 Diabetes on Bone Biomechanics

Abstract

Purpose of Review

Recent Findings

Summary

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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