Sclerostin levels associated with inhibition of the Wnt/β-catenin signaling and reduced bone turnover in type 2 diabetes mellitus.

Abstract

Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. This was a cross-sectional study. The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50-2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20-7.62, respectively; P=0.0002). β-Catenin correlated negatively with sclerostin (P<0.0001) and positively with bone alkaline phosphatase (P=0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.