Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture. Because osteoporotic fractures such as hip and vertebral fractures increase mortality in the general population, diabetes-related bone fragility may also be associated with mortality in patients with diabetes mellitus. However, no studies have investigated whether bone metabolism or the prevalence of osteoporotic fractures is involved in the mortality of patients with T2DM.

Subjects and Methods: This historical cohort study assessed the endpoint of all-cause mortality in patients with T2DM. The associations of bone turnover markers, bone mineral density (BMD), and the prevalence of vertebral fractures with mortality were investigated by unadjusted survival and Cox regression analyses adjusted for age, gender, diabetes duration, hemoglobin A1c (HbA1c) level, body mass index, and serum creatinine level.

Results: Of 411 patients, 56 died during the follow-up period of almost seven 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] = 2.66, 95% confidence interval [CI] 1.25-5.66, p = 0.011 for LS-T score ≤-2.5; HR = 4.92, 95% CI 1.74-13.86, p = 0.003 for FN-T score ≤-2.5; HR = 2.74, 95% CI 1.39-5.37, p = 0.003 for multiple vertebral fractures; HR = 6.16, 95% CI 2.12-17.94, p < 0.001 for grade 3 vertebral fracture). Separate analysis in men and women showed that decreased serum osteocalcin was associated with mortality only in women (HR = 0.30, 95% CI 0.11-0.80 per SD increase, p = 0.016), but not BAP or urinary NTX was not associated in men and women.

Conclusion: The present study is the first to show the association of lower serum osteocalcin levels, reduced BMD, and severe vertebral fractures with increased all-cause mortality in patients with T2DM.