Current Osteoporosis Reports

, Volume 10, Issue 1, pp 73–79 | Cite as

Inhibition of Cathepsin K for Treatment of Osteoporosis

  • Steven Boonen
  • Elizabeth Rosenberg
  • Frank Claessens
  • Dirk Vanderschueren
  • Socrates Papapoulos
Future Therapeutics (P Miller, Section Editor)


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.


Cathepsin K inhibition Osteoporosis 



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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Steven Boonen
    • 1
  • Elizabeth Rosenberg
    • 2
  • Frank Claessens
    • 3
  • Dirk Vanderschueren
    • 4
  • Socrates Papapoulos
    • 5
  1. 1.Leuven University Division of Geriatric Medicine and Centre for Metabolic Bone DiseasesLeuvenBelgium
  2. 2.Merck Sharp & Dohme Corp.Whitehouse StationUSA
  3. 3.Leuven University Department of Molecular Cell BiologyLeuvenBelgium
  4. 4.Leuven University Department of Andrology and EndocrinologyLeuvenBelgium
  5. 5.Leiden University Medical CenterLeidenNetherlands

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