Differential risk of fracture attributable to type 2 diabetes mellitus according to skeletal site.

Abstract

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). 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. 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. 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). 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.