Elevated Sclerostin Levels Are Associated With Vertebral Fractures in Patients With Type 2 Diabetes Mellitus

Context: Patients with type 2 diabetes mellitus (T2DM) patients are at increased risk of vertebral fractures (VFs) compared with non-T2DM individuals, because of poor bone quality. Recent studies in nondiabetic subjects have shown that elevated sclerostin levels are associated with VFs independent of bone mineral density (BMD). Objective: We aimed to investigate the association between sclerostin levels and VFs in T2DM. Research Design and Methods: We conducted a cross-sectional observational study in 146 postmenopausal women and 175 men over 50 years old. Sclerostin levels were compared in the patients with and without VFs confirmed by spinal radiographs. Results: Sclerostin levels were significantly higher in men than in women (P < .01). Stepwise forward multiple regression analyses demonstrated that spine BMD was the strongest and independent positive determinant for sclerostin in both genders. When the participants were divided into 2 subgroups by the T score of spine BMD to eliminate the influence of BMD on sclerostin values, elevated sclerostin levels were associated with an increased risk of VFs in the male patients with BMD T scores >= -1 (odds ratio = 1.85, 95% confidence interval = 1.12-3.07) and female with T scores < -1 (odds ratio = 3.23, 95% confidence interval = 1.42-7.34) after adjusting for multiple variables including BMD and bone metabolic markers. Conclusions: Elevated sclerostin levels were associated with an increased risk of VFs in T2DM patients independently of BMD and bone turnover in both genders, suggesting that sclerostin levels may reflect bone fragility attributed to the deterioration of bone quality under the gender-specific range of BMD T scores.