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Inhibition of Cathepsin K for Treatment of Osteoporosis

  • Future Therapeutics (P Miller, Section Editor)
  • Published:
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Abstract

Cathepsin K is the protease that is primarily responsible for the degradation of bone matrix by osteoclasts. Inhibitors of cathepsin K are in development for treatment of osteoporosis. Currently available antiresorptive drugs interfere with osteoclast function. They inhibit both bone resorption and formation, due to the coupling between these processes. Cathepsin K inhibitors, conversely, target the resorption process itself and may not interfere with osteoclast stimulation of bone formation. In fact, when cathepsin K is absent or inhibited in mice, rabbits, or monkeys, bone formation is maintained or increased. In humans, inhibition of cathepsin K is associated with sustained reductions in bone resorption markers but with smaller and transient reductions in bone formation markers. The usefulness of cathepsin K inhibitors in osteoporosis is now being examined in phase 2 and phase 3 clinical trials of postmenopausal osteoporotic women.

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Disclosure

Conflicts of interest: S. Boonen: received editorial support from Dr. Rosenberg who is an employee of Merck; has received payment for lectures including service on speakers bureaus for Amgen, Novartis, and Servier; and has received travel/accommodations/meeting expenses from Amgen, Novartis, and Servier for Congress participation; E. Rosenberg: is employed by and has stock options in Merck Sharp & Dohme; F. Claessens: none; D. Vanderschueren: none; S. Papapoulos: has been a board member for Merck & Co Advisory Board, Amgen, Novartis; has been a consultant for Merck & Co, Alliance for Better Bone Health, Amgen, Roche, GlaxoSmithKline; and has received honoraria from all above-mentioned entities in relation to participation in AdB and Consultancies; and has received travel/accommodations expenses covered or reimbursed from all above-mentioned entities in relation to participation in AdB.

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Authors and Affiliations

  1. Leuven University Division of Geriatric Medicine and Centre for Metabolic Bone Diseases, UZ Leuven campus Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium

    Steven Boonen

  2. Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA

    Elizabeth Rosenberg

  3. Leuven University Department of Molecular Cell Biology, Leuven, Belgium

    Frank Claessens

  4. Leuven University Department of Andrology and Endocrinology, Leuven, Belgium

    Dirk Vanderschueren

  5. Leiden University Medical Center, Leiden, Netherlands

    Socrates Papapoulos

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  1. Steven Boonen
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  2. Elizabeth Rosenberg
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  4. Dirk Vanderschueren
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  5. Socrates Papapoulos
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Correspondence to Steven Boonen.

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Boonen, S., Rosenberg, E., Claessens, F. et al. Inhibition of Cathepsin K for Treatment of Osteoporosis. Curr Osteoporos Rep 10, 73–79 (2012). https://doi.org/10.1007/s11914-011-0085-9

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  • DOI: https://doi.org/10.1007/s11914-011-0085-9

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