Future of anticathepsin K drugs: dual therapy for skeletal disease and atherosclerosis?

BACKGROUND: Until fairly recently, cathepsin K was recognized solely as a bone-resorbing enzyme expressed selectively in the osteoclast. Evidence of its requirement for normal bone remodeling has resulted in this protease receiving considerable attention from the pharmaceutical industry. In the last decade, intense research efforts were aimed at development of cathepsin K inhibitors for treatment of osteoporosis and other skeletal disorders associated with pathological bone loss. Emerging new evidence suggests that in addition to bone resorption, cathepsin K is involved in the turnover of extracellular matrix proteins in organs, such as the lung, thyroid and skin, and plays important roles in cardiovascular disease, inflammation and obesity. DISCUSSION: This review highlights the physiological and pathophysiological implications of this potent protease, with a focus on recent developments in the design and use of cathepsin K inhibitors to target skeletal pathologies. Therapeutic implications of anticathepsin K drugs in the context of common links between bone disease and atherosclerosis are also discussed.
CONCLUSION: The association of cathepsin K with skeletal and cardiovascular disorders offers intriguing future applications for inhibitors of this potent protease.