Bone Sclerostin and Dickkopf-related protein-1 are positively correlated with bone mineral density, bone microarchitecture, and bone strength in postmenopausal osteoporosis
Jia Peng, Dong Zhang, Hui Zhang, Wang Aifei, Deng Lianfu, Youjia Xu
Abstract
BACKGROUND: Wnt-catenin signaling antagonists sclerostin and dickkopf-related protein-1 (Dkk-1) inhibit bone formation and are involved in the pathogenesis of postmenopausal osteoporosis (PO). However, the association between sclerostin and Dkk-1 and bone mineral density (BMD) in women with PO remains unclear. OBJECTIVE: This study aimed to determine the association between sclerostin and Dkk-1 and BMD, bone microarchitecture, and bone strength in PO. METHODS: Trabecular bone specimens were obtained from the femoral heads of 76 Chinese women with PO who underwent hip arthroplasty for femoral neck fractures. Micro-computed tomography (Micro-CT) was used to assess the BMD and bone microarchitecture of the trabecular bone. Subsequently, a mechanical test was performed. Finally, sclerostin and Dkk-1 in the bone were measured by enzyme-linked immunosorbent (Elisa) assay. Serum ionized serum ionised calcium, propeptide of type 1 collagen, C-terminal β-telopeptide of type-1 collagen, sclerostin, and Dkk-1 were also detected. RESULTS: Bone sclerostin was positively correlated with serum ionised calcium, serum sclerostin, BMD, bone volume/tissue volume (BV/TV), trabecular number (Tb.N), maximum compressive force, and yield strength (r = 0.32, 0.906, 0.355, 0.401, 0.329, 0.355, and 0.293, respectively, P < 0.05) and negatively correlated with age and trabecular separation (Tb.Sp) (r = - 0.755 and - 0.503, respectively, P < 0.05). Bone Dkk-1 was positively correlated with serum ionised calcium, serum Dkk-1, BMD, BV/TV, trabecular thickness, Tb.N, maximum compressive force, yield strength, and Young's modulus (r = 0.38, 0.809, 0.293, 0.293, 0.228, 0.318, 0.352, 0.315, and 0.266, respectively, P < 0.05) and negatively correlated with age and Tb.Sp (r = - 0.56 and - 0.38, respectively, P < 0.05). Serum levels of sclerostin and Dkk-1 reflected the levels of sclerostin and Dkk-1 in the bone. CONCLUSION: Bone sclerostin and Dkk-1 were positively correlated with BMD in women with PO, and higher levels of bone sclerostin and Dkk-1 might predict better BMD, bone microarchitecture, and bone strength. The potential molecular mechanisms still require further study.