Highlights of the 28th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR)

September 15-19, 2006; Philadelphia, Pennsylvania

Ego Seeman, MD


January 11, 2007

In This Article

Cathepsin K Inhibitors

Dissolution of mineral exposes the organic matrix to proteolytic enzymes, particularly cathepsin K, a cysteine protease expressed in osteoclasts, which degrades type I collagen. Cathepsin K inhibitors may also reduce bone resorption, but not bone formation, perhaps in part because inhibition of osteoclastic resorption in this manner does not impair osteoblastogenesis and in part because there may be transitory increases in PTH. An investigational cathepsin K inhibitor, balicatib, was shown to reduce bone resorption as measured by bone remodeling markers, but no inhibitory effect on bone formation markers was observed.[24] Adami and colleagues[25] addressed why bone formation may not be suppressed by balicatib, reporting that collagen degradation is inhibited, but not earlier osteoclast function, which is likely to be important in osteoblastogenesis. In 675 women, treatment with 1 regimen of balicatib increased BMD at the spine and hip, while remodeling markers decreased and formation markers remained unchanged or increased. Similar dissociation in markers of formation and resorption were reported by Papanastasiou and colleagues[26] in a 12-week trial involving 140 postmenopausal women treated with different doses of balicatib. The drug is potentially important because it may reduce fracture risk by both rapidly reducing bone resorption and increasing bone formation. Much more work will be needed before this mechanism can be inferred.


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