Risk of fracture in women with type 2 diabetes:​ the Women’s Health Initiative Observational Study

Bonds, Denise E.<sup>1</sup>; Larson, Joseph C.<sup>2</sup>; Schwartz, Ann V.<sup>3</sup>; Strotmeyer, Elsa S.<sup>4</sup>; Robbins, John<sup>5</sup>; Rodriguez, Beatriz L.<sup>6</sup>; Johnson, Karen C.<sup>7</sup>; Margolis, Karen L.<sup>8</sup>

Affiliations

¹Departments of Epidemiology and Prevention and Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

²Fred Hutchinson Cancer Research Center, Seattle, Washington 98109

³Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94105

⁴Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

⁵Department of Internal Medicine, University of California, Davis, Davis, California 95817

⁶Department of Geriatric Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96817

⁷Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis Tennessee 38105

⁸HealthPartners Research Foundation, Minneapolis, Minnesota 55440-1524

Abstract

Context: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes.

Objective: The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density.

Design, Setting, and Participants: Women with clinically diagnosed type 2 diabetes at baseline in the Women’s Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined.

Main Outcome Measures: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured.

Results: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls [adjusted relative risk (RR) 1.20, 95% confidence interval (CI) 1.11–1.30]. In a subsample of women with baseline BMD scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone) among black women (RR 1.33, 95% CI 1.00–1.75) and women with increased baseline bone density (RR 1.26, 95% CI 0.96–1.66).

Conclusion: Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).

Links

DOI: 10.1210/jc.2006-0614

PubMed: 16804043

WoS: 000240358600025

History

Received: 2006-03-20

Accepted: 2006-06-15

Online: 2006-06-27

Cited Works (3)

Year	Entry
1996	Paul RG, Bailey AJ. Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol. December 1996;28(12):1297-1310.
2002	Wang X, Shen X, Li X, Agrawal CM. Age-related changes in the collagen network and toughness of bone [published correction appears in Bone. 2003;32(1):107]. Bone. 2002;31(1):1-7.
2004	Johnell O, Kanis JA, Odén A, Sernbo I, Redlund-Johnell I, Petterson C, De Laet C, Jönsson B. Mortality after osteoporotic fractures. Osteoporos Int. January 2004;15(1):38-42.

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2016	Farr JN, Khosla S. Determinants of bone strength and quality in diabetes mellitus in humans. Bone. January 2016;82:28-34.
2020	Vilaca T, Schini M, Harnan S, Sutton A, Poku E, Allen IE, Cummings SR, Eastell R. The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: a systematic review and meta-analysis update. Bone. August 2020;137:115457.
2021	Park SK, Jung JY, Oh C-M, Choi J-M, Kim M-H, Ha E, Ryoo J-H. Fasting glucose level and the risk of incident osteoporosis in the Koreans. Bone. January 2021;142:115690.
2021	Zhou J, Li H, Chang C, Wu WKK, Wang X, Liu T, Cheung BMY, Zhang Q, Lee S, Tse G. The association between blood pressure variability and hip or vertebral fracture risk: a population-based study. Bone. September 2021;150:116015.
2022	LLabre JE, Sroga GE, Tice MJ, Vashishth D. Induction and rescue of skeletal fragility in a high-fat diet mouse model of type 2 diabetes: an in vivo and in vitro approach. Bone. March 2022;156:116302.
2022	Palomo T, Dreyer P, Muszkat P, Weiler FG, Bonansea TCP, Domingues FC, Vieira JGH, Silva BC, Brandão CMA. Effect of soft tissue noise on trabecular bone score in postmenopausal women with diabetes: a cross sectional study. Bone. April 2022;157:116339.
2020	Yasui H, Yano K, Kuzuhara Y, Ikegawa M, Matsukawa M. Prolonged hyperglycemia reduces elasticity of type II diabetic rat bone. Calcif Tiss Int. October 2020;107(4):381-388.
2011	Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, Donaldson MG, Cauley JA, Harris TB, Koster A, Womack CR, Palermo L, Black DM; Study of Osteoporotic Fractures (SOF); Osteoporotic Fractures in Men (MrOS); Health, Aging, and Body Composition (Health ABC) Research Groups. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. June 1, 2011;305(21):2184-2192.
2012	Giangregorio LM, Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA. FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res. February 2012;27(2):301-308.
2014	Farr JN, Drake MT, Amin S, Melton LJ III, McCready LK, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res. April 2014;29(4):787-795.
2017	Nilsson AG, Sundh D, Johansson L, Nilsson M, Mellström D, Rudäng R, Zoulakis M, Wallander M, Darelid A, Lorentzon M. Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: a population‐based study. J Bone Miner Res. May 2017;32(5):1062-1071.
2018	Samelson EJ, Demissie S, Cupples LA, Zhang X, Xu H, Liu C-T, Boyd SK, McLean RR, Broe KE, Kiel DP, Bouxsein ML. Diabetes and deficits in cortical bone density, microarchitecture, and bone size: Framingham HR-pQCT study. J Bone Miner Res. January 2018;33(1):54-62.
2019	Hunt HB, Torres AM, Palomino PM, Marty E, Saiyed R, Cohn M, Jo J, Warner S, Sroga GE, King KB, Lane JM, Vashishth D, Hernandez CJ, Donnelly E. Altered tissue composition, microarchitecture, and mechanical performance in cancellous bone from men with type 2 diabetes mellitus. J Bone Miner Res. July 2019;34(7):1191-1206.
2020	Cauley JA, Crandall C. The Women's Health Initiative: a landmark resource for skeletal research since 1992. J Bone Miner Res. May 2020;35(5):845-860.
2021	Hunt HB, Miller NA, Hemmerling KJ, Koga M, Lopez KA, Taylor EA, Sellmeyer DE, Moseley KF, Donnelly E. Bone tissue composition in postmenopausal women varies with glycemic control from normal glucose tolerance to type 2 diabetes mellitus. J Bone Miner Res. February 2021;36(2):334-346.
2023	Lekkala S, Sacher SE, Taylor EA, Williams RM, Moseley KF, Donnelly E. Increased advanced glycation endproducts, stiffness, and hardness in iliac crest bone from postmenopausal women with type 2 diabetes mellitus on insulin. J Bone Miner Res. February 2023;38(2):261-277.
2020	Eckhardt BA, Rowsey JL, Thicke BS, Fraser DG, O’Grady KL, Bondar OP, Hines JM, Singh RJ, Thoreson AR, Rakshit K, Lagnado AB, Passos JF, Vella A, Matveyenko AV, Khosla S, Monroe DG, Farr JN. Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes. JCI Insight. May 7, 2020;5(9):135236.
2008	Melton LJ III, Riggs BL, Leibson CL, Achenbach SJ, Camp JJ, Bouxsein ML, Atkinson EJ, Robb RA, Khosla S. A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab. December 2008;03(12):4804-4809.
2016	Furst JR, Bandeira LC, Fan W-W, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR. Advanced glycation endproducts and bone material strength in type 2 diabetes. J Clin Endocrinol Metab. June 2016;101(6):2502-2510.
2017	Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL; IOF Bone and Diabetes Working Group. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. April 2017;13(4):208-219.
2018	Hunt HB. Characterization of Material Properties, Microarchitecture, and Mechanics of Bone from Subjects With Type 2 Diabetes Mellitus [PhD thesis]. Ithaca, NY: Cornell University; December 2018.
2020	Lekkala S. Characterization of Material and Compositional Properties of Iliac Bone from Postmenopausal Women With Worsening Glycemic Control [Master's thesis]. Ithaca, NY: Cornell University; August 2020.
2020	Taylor EA. Validation and Implementation of Vibrational Spectroscopic Measures of Bone Composition [PhD thesis]. Ithaca, NY: Cornell University; December 2020.
2021	Sacher S. Characterization of Trabecular Morphology, Microdamage Accumulation, and Collagen Crosslinking in Bone Tissue from Individuals With Type II Diabetes Mellitus [Master's thesis]. Ithaca, NY: Cornell University; May 2021.
2016	Oei L. Epidemiological, Radiological and Genetic Aspects of Endocrine Bone Diseases [PhD thesis]. Erasmus University Rotterdam; December 14, 2016.
2021	Hays MR. Effects of Metformin on Advanced Glycation End Product Formation in Bone Under Hyperglycemic Conditions [Master's thesis]. University of Massachusetts at Dartmouth; May 2021.
2021	Vaidya RS. Diabetes Associated Alterations in Osteocytic Regulation of Bone Remodelling [PhD thesis]. University of Massachusetts at Dartmouth; August 2021.
2022	Rezaee T. Effect of Clinically Relevant Alterations of Mineral and Protein on Bone Biomechanics [PhD thesis]. University of Massachusetts at Dartmouth; May 2022.
2022	Snow TJ. An Investigation of the Role of Collagen Network on the Dynamic Fracture Initiation Toughness of Bovine Cortical Bone [Master's thesis]. University of Utah; December 2022.