Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus

Abstract

AIM: Type 1 diabetes mellitus (T1DM) increases fragility fractures due to low bone mass, micro-architectural alterations and decreased bone formation. Sclerostin is expressed by osteocytes and inhibits osteoblastic bone formation. We evaluated serum sclerostin levels in T1DM and their association with bone mineral density (BMD), bone turnover, glycaemic control and physical activity. PATIENTS AND METHODS: In a cross-sectional study, 128 men and premenopausal women with long-standing T1DM (mean age 43·4 ± 8·8 years, diabetes duration 22·4 ± 9·5 years) and 77 age-, BMI (Body Mass Index) and gender-matched healthy individuals were evaluated. RESULTS: Serum sclerostin levels were higher in T1DM compared with controls, irrespective of gender (male 0·55 ± 0·17 vs 0·49 ± 0·12 ng/ml, P = 0·046; female 0·52 ± 0·19 ng/ml vs 0·43 ± 0·12 ng/ml, P = 0·012). Partial correlation analysis adjusted for age and gender revealed a positive correlation between serum sclerostin levels and BMD at lumbar spine and femoral neck in T1DM and between BMD at lumbar spine, femoral neck and total hip in controls. Bone turnover markers, parathyroid hormone, calcium and vitamin D did not correlate with serum sclerostin levels in T1DM or controls. Physical activity was not associated with serum sclerostin levels. A multivariate analysis revealed that only the interaction of T1DM and age affects serum sclerostin levels but not T1DM alone. The influence of age on serum sclerostin levels was more pronounced in T1DM compared with controls. CONCLUSIONS: Sclerostin serum levels were increased in patients with T1DM, and the positive correlation of age with serum sclerostin levels was stronger in T1DM. There was no effect of serum sclerostin levels on markers of bone metabolism and they do not explain the detrimental effects of T1DM on BMD.