期刊
THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE
卷 5, 期 4, 页码 199-209出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1759720X13490860
关键词
animal models; bone demineralization; bone density conservation agents; bone remodeling; cathepsin K; osteoporosis postmenopausal; pathologic
类别
资金
- Pfizer
- Sanofi
- GSK
- Amgen
- Lilly
- Merck
- Ache
- Servier
- Novartis
- Warner-Chilcott
Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding of the molecular and cellular mechanisms involved in the remodeling process have allowed the development of new targets for osteoporosis treatment. Cathepsin K, a cysteine protease, is found in osteoclasts along the bone resorption surfaces and very efficiently degrades type I collagen, the major component of the organic bone matrix. Inhibition of cathepsin K reduces bone resorption but does not impair bone formation particularly at cortical sites. Odanacatib, a potent and highly selective cathepsin K inhibitor, showed prevention of bone loss without reduction of bone formation in preclinical and clinical trials (phase I and II). Odanacatib is currently in a phase III fracture outcome international trial for the treatment of postmenopausal osteoporosis.
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