Differential risk of fracture attributable to type 2 diabetes mellitus according to skeletal site
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BACKGROUND: Impaired bone quality, especially related to accumulation of advanced glycation end-products (AGEs) and higher incidence of falls contribute substantially to a higher risk of fracture associated with type 2 diabetes mellitus (T2DM). These factors may predispose to fractures more at skeletal sites where impaired bone toughness and falls play a larger pathogenic role (such as hip fractures) compared to skeletal sites where they are less important (such as vertebral fractures). OBJECTIVE: To determine if the associations of T2DM with prevalent and incident vertebral fractures are as strong as they are for hip and other non-vertebral fractures. METHODS: Amongst 80,238 individuals in the Manitoba Bone Density Program database (mean [SD] age 64.4 [11.1] years, 89.8% female, 8676 with diagnosed T2DM) with a baseline BMD test (1996-2016), we estimated hazard ratios (HRs) for incident clinical fracture at different skeletal sites in those with compared to those without T2DM using Cox proportional hazards models over a mean (SD) 9.0 (5.0) year follow-up period. We also estimated odds ratios for prevalent vertebral fracture on VFA images amongst 9594 individuals (mean [SD] 76 [6.8] years, 1185 with T2DM diagnosis at time of DXA-VFA) and for prior clinical fractures at different skeletal sites using logistic regression models. RESULTS: After multivariable adjustment, T2DM was associated with incident hip (HR 1.63, 95% CI 1.44 to 1.85) and proximal humerus fractures (HR 1.59, 95% CI 1.39 to 1.83), but was not associated with incident forearm fracture (HR 1.00, 95% CI 0.86 to 1.17) and only weakly with incident clinical vertebral fracture (HR 1.16, 95% CI 1.01 to 1.33). Similarly, T2DM was associated with prior hip (OR 1.78, 95% CI 1.21 to 2.61) and prior proximal humerus fracture (OR 1.31, 95% CI 1.02 to 1.68) but not with prior forearm (OR 0.89, 95% CI 0.74 to 1.06) or prevalent vertebral fracture on VFA images (OR 0.91, 95% CI 0.77 to 1.08). CONCLUSION: T2DM is a stronger risk factor for hip and proximal humerus fractures than for vertebral and wrist fractures. Further research is warranted to determine if the known differences in falls and/or bone quality between T2DM and age-related osteoporosis account for these differential associations.
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