Update in osteoporosis and metabolic bone disorders.
Update in osteoporosis and metabolic bone disorders.
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DOI：
10.1210/jc.2007-0042
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发表时间：
2007-03
期刊：
影响因子：
--
通讯作者：
D. Shoback
中科院分区：
文献类型：
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作者：
D. Shoback
在开发和测试治疗骨质疏松症的药物方面已经取得了相当大的进展。最令人印象深刻的是关于新的抗骨吸收剂的报道--双膦酸盐（伊班膦酸盐和唑来膦酸）和针对核因子κ B-配体受体激活剂的单克隆抗体（狄诺塞麦），核因子κ B-配体是控制破骨细胞定型和激活的关键分子。双膦酸盐有望在减缓骨丢失方面提供便利性和效力，而狄诺塞单抗则提供了强大的再吸收抑制和快速抵消作用。人们的注意力也从作为新疗法靶点的破骨细胞转移到成骨细胞和骨细胞，它们在骨的深处具有复杂的网络。Wnt信号通过卷曲受体及其辅助受体，低密度脂蛋白受体相关蛋白-5，从分子和体内证据看来是一个关键的途径，用于调节成骨细胞的活性，骨形成，骨强度。最近鉴定的SOST基因或sclerostin的产物也显示出阻断Wnt信号传导。骨硬化素是由埋藏在骨中的骨细胞产生的，是治疗骨丢失的新靶点。临床试验报告表明，拟钙剂西那卡塞可有效治疗原发性和继发性甲状旁腺功能亢进和甲状旁腺癌引起的PTH分泌过多。最后，现在认识到基质蛋白质牙本质基质蛋白-1增强磷酸盐调节因子成纤维细胞生长因子23的释放，并且牙本质基质蛋白-1中的突变在低磷酸盐血症性佝偻病的形式中起致病作用。
Considerable progress has been made in the development and testing of agents to treat osteoporosis. Most impressive are reports on new antiresorptive agents--both bisphosphonates (ibandronate and zoledronic acid) and monoclonal antibodies (MAbs) (denosumab) directed against receptor activator of nuclear factor kappaB-ligand, a key molecule in the control of commitment and activation of osteoclasts. Bisphosphonates promise convenience and potency at slowing bone loss, whereas denosumab offers powerful suppression of resorption and rapid offset of action. Attention is also shifting from the osteoclast as a target for new therapies to the osteoblast and the osteocyte, with its complex network within the depths of bone. Wnt signaling through the frizzled receptor and its coreceptor, the low-density lipoprotein receptor related protein-5, appears from both molecular and in vivo evidence to be a pivotal pathway for modulating osteoblastic activity, bone formation, and bone strength. The recently identified product of the SOST gene or sclerostin has also been shown to block Wnt signaling. Sclerostin is produced by the osteocytes buried in the bone and is a new target to treat bone loss. Clinical trial reports indicate that the calcimimetic cinacalcet can effectively treat PTH hypersecretion due to primary and secondary hyperparathyroidism and parathyroid carcinoma. Lastly, it is now recognized that the matrix protein dentin matrix protein-1 enhances the release of the phosphate-regulating factor fibroblast growth factor 23 and that mutations in dentin matrix protein-1 play a causative role in a form of hypophosphatemic rickets.