Department of Orthopaedic, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China.
PLoS One. 2012;7(7):e40272. doi: 10.1371/journal.pone.0040272. Epub 2012 Jul 6.
Treatment for osteoporosis commonly includes the use of bisphosphonates. Serious side effects of these drugs are caused by the inhibition of bone resorption as a result of osteoclast apoptosis. Treatment using calcitonin along with bisphosphonates overcomes these side-effects in some patients. Calcitonin is known to inhibit bone resorption without reducing the number of osteoclasts and is thought to prolong osteoclast survival through the inhibition of apoptosis. Further understanding of how calcitonin inhibits apoptosis could prove useful to the development of alternative treatment regimens for osteoporosis. This study aimed to analyze the mechanism by which calcitonin influences osteoclast apoptosis induced by a bisphosphate analog, sintered dicalcium pyrophosphate (SDCP), and to determine the effects of co-treatment with calcitonin and SDCP on apoptotic signaling in osteoclasts.
Isolated osteoclasts were treated with CT, SDCP or both for 48 h. Osteoclast apoptosis assays, pit formation assays, and tartrate-resistant acid phosphatase (TRAP) staining were performed. Using an osteoporosis rat model, ovariectomized (OVX) rats received calcitonin, SDCP, or calcitonin + SDCP. The microarchitecture of the fifth lumbar trabecular bone was investigated, and histomorphometric and biochemical analyses were performed.
Calcitonin inhibited SDCP-induced apoptosis in primary osteoclast cultures, increased Bcl-2 and Erk activity, and decreased Mcl-1 activity. Calcitonin prevented decreased osteoclast survival but not resorption induced by SDCP. Histomorphometric analysis of the tibia revealed increased bone formation, and microcomputed tomography of the fifth lumbar vertebrate showed an additive effect of calcitonin and SDCP on bone volume. Finally, analysis of the serum bone markers CTX-I and P1NP suggests that the increased bone volume induced by co-treatment with calcitonin and SDCP may be due to decreased bone resorption and increased bone formation.
Calcitonin reduces SDCP-induced osteoclast apoptosis and increases its efficacy in an in vivo model of osteoporosis.
骨质疏松症的治疗通常包括使用双膦酸盐。这些药物的严重副作用是由于破骨细胞凋亡导致的骨吸收抑制引起的。在一些患者中，使用降钙素联合双膦酸盐治疗可以克服这些副作用。降钙素已知可抑制骨吸收而不减少破骨细胞数量，并通过抑制细胞凋亡来延长破骨细胞的存活时间。进一步了解降钙素如何抑制细胞凋亡可能有助于开发骨质疏松症的替代治疗方案。本研究旨在分析降钙素影响双膦酸盐类似物烧结二磷酸钙（SDCP）诱导的破骨细胞凋亡的机制，并确定降钙素和 SDCP 联合治疗对破骨细胞凋亡信号的影响。
用 CT、SDCP 或两者联合处理分离的破骨细胞 48 小时。进行破骨细胞凋亡试验、陷窝形成试验和抗酒石酸酸性磷酸酶（TRAP）染色。使用骨质疏松症大鼠模型，卵巢切除（OVX）大鼠接受降钙素、SDCP 或降钙素+SDCP。研究第五腰椎小梁骨的微观结构，并进行组织形态计量学和生化分析。
降钙素抑制原代破骨细胞培养物中 SDCP 诱导的细胞凋亡，增加 Bcl-2 和 Erk 活性，降低 Mcl-1 活性。降钙素可防止 SDCP 诱导的破骨细胞存活减少，但不能防止其吸收减少。胫骨的组织形态计量学分析显示骨形成增加，第五腰椎椎体的微计算机断层扫描显示降钙素和 SDCP 联合使用对骨量有相加作用。最后，分析血清骨标志物 CTX-I 和 P1NP 表明，降钙素和 SDCP 联合治疗诱导的骨量增加可能是由于骨吸收减少和骨形成增加所致。
降钙素可减少 SDCP 诱导的破骨细胞凋亡，并提高其在骨质疏松症体内模型中的疗效。
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