Nagase Yuichi, Tanaka Sakae
Department of Orthopaedic Sugery, The University of Tokyo Hospital.
Clin Calcium. 2011 Jan;21(1):59-62.
Bone homeostasis is maintained by delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bisphosphonates are widely used nowadays by suppressing bone resorption to treat patients with osteoporosis, which results from high bone turnover, causing excessive bone resorption phase. While bisphosphonates increase bone mineral density and improve back pain due to spinal compression fracture, they may have some problems such as osteonecrosis of jaw and excessive suppression of bone turnover. Cathepsin K inhibitor, which has a new mechanism in addition to function of suppressing bone resorption, is recently focused. Cathepsin K is a protease which specifically expresses in osteoclasts and plays an important role in resolution of bone collagen. Cathepsin K inhibitor has a potential of inhibiting bone resorption without suppressing bone formation and could be an attractive therapeutic target of osteoporosis.
骨稳态通过破骨细胞的骨吸收和成骨细胞的骨形成之间的微妙平衡来维持。双膦酸盐目前被广泛用于通过抑制骨吸收来治疗骨质疏松症患者，骨质疏松症是由高骨转换导致过度骨吸收阶段引起的。虽然双膦酸盐可增加骨矿物质密度并改善因脊柱压缩性骨折引起的背痛，但它们可能存在一些问题，如颌骨坏死和过度抑制骨转换。组织蛋白酶K抑制剂除了具有抑制骨吸收的功能外还具有新机制，最近受到关注。组织蛋白酶K是一种在破骨细胞中特异性表达的蛋白酶，在骨胶原分解中起重要作用。组织蛋白酶K抑制剂具有在不抑制骨形成的情况下抑制骨吸收的潜力，可能是一种有吸引力的骨质疏松症治疗靶点。
