Role of sclerostin and dkk1 in bone remodeling in type 2 diabetic patients

Abstract

Purpose: This study aimed to investigate the role of sclerostin and dkk1 in the bone metabolism of type 2 diabetic patients. Methods: This cross-sectional study included 95 inpatients with type 2 diabetes mellitus. We divided the patients into three groups (i.e., the normal bone mineral density (BMD) group, osteopenia group and osteoporosis group) based on their different BMD levels and measured the serum levels of sclerostin, dkk1, 25-hydroxyvitamin D₃ (25OHD₃), bone turnover markers and other biochemical data in each group. Results: Significantly increased levels of serum sclerostin and dkk1 were found in the osteoporosis group, even when the male and female cohorts were considered separately. Ordinal logistic regression analysis suggested that the levels of serum sclerostin were independently associated with the presence of osteopenia and osteoporosis after adjusting for age, gender and 25OHD₃ (sclerostin: OR = 1.02, p = 0.001). The areal BMDs were negatively correlated with the levels of serum sclerostin and dkk1 and positively correlated with 25OHD₃. In addition, age, glycosylated hemoglobin and serum sclerostin levels were predictors for N-terminal propeptide of type 1 procollagen and serum dkk1 levels were the only predictors for crosslinked carboxyterminal telopeptide in type 1 collagen. Conclusions: The sclerostin and dkk1 levels increased in conjunction with the reduction of BMD, confirming that the Wnts, inhibited by sclerostin and dkk1, were potentially responsible for bone fragility in type 2 diabetes patients with osteoporosis. Note that the serum sclerostin levels were predictors for bone formation, while the DKK1 levels predicted bone resorption.