Association of Bone Mineral Density, Bone Turnover Markers, and Vertebral Fractures with All-Cause Mortality in Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture. However, the association between diabetes-related osteoporosis and mortality in T2DM remains unknown. This historical cohort study assessed the endpoint of all-cause mortality in patients with T2DM. According to our hospital record, bone parameters were examined in 797 patients from 1997 to 2009. We excluded 78 because of diseases affecting bone metabolism and could not follow-up 308 patients. Finally, in 411 patients, the associations of bone turnover markers, bone mineral density (BMD), and the prevalence of vertebral fractures with mortality were investigated by Cox regression analyses adjusted for confounding factors. Of 411 patients, 56 died during the follow-up period of almost 7 years. Cox regression analyses showed that reduced BMD at the lumbar spine (LS) and femoral neck (FN) (T-score ≤ -2.5) and severe vertebral fractures were associated with higher mortality (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.48-7.16, p = 0.003 for LS-T score ≤ -2.5; HR 5.19, 95% CI 1.83-14.75, p = 0.002 for FN-T score ≤ -2.5; HR 2.93, 95% CI 1.42-6.02, p = 0.004 for multiple vertebral fractures; HR 7.64, 95% CI 2.13-27.42, p = 0.002 for grade 3 vertebral fracture). Separate analysis in men and women showed that decreased serum osteocalcin was associated with mortality in women (HR 3.82, 95% CI 1.01-14.46 per SD decrease, p = 0.048). The present study is the first to show the association of reduced BMD and severe vertebral fractures with increased all-cause mortality in patients with T2DM. Moreover, higher serum osteocalcin was significantly associated with decreased mortality in women with T2DM.