Jia Peng1,2, Zhang Dong2, Zhang Hui1, Wang Aifei1, Deng Lianfu3,4,5, Xu Youjia6,7. 1. Orthopedic Department, Second Affiliated Hospital of Soochow University, Suzhou, China. 2. Second Affiliated Hospital of Soochow University, Osteoporosis Research Institute of Soochow University, Suzhou, China. 3. Shanghai Institute of Traumatology and Orthopedics, Shanghai, China. lianfu_deng@163.com. 4. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai, China. lianfu_deng@163.com. 5. Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai, China. lianfu_deng@163.com. 6. Orthopedic Department, Second Affiliated Hospital of Soochow University, Suzhou, China. xuyoujia@suda.edu.cn. 7. Second Affiliated Hospital of Soochow University, Osteoporosis Research Institute of Soochow University, Suzhou, China. xuyoujia@suda.edu.cn.
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.
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 withage 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 withage 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 withBMD 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.
Entities:
Keywords:
Bone microarchitecture; Bone mineral density; Bone strength; Dickkopf-related protein-1; Postmenopausal osteoporosis; Sclerostin
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