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[Cathepsin K antagonists: preclinical and clinical data]
Marion Gamsjäger1, Heinrich Resch
1II. Medizinische Abteilung (Rheumatologie/Osteologie & Gastroenterologie), KH Barmherzige Schwestern, Akademisches Lehrkrankenhaus der MUW, 1060, Wien, Stumpergasse 13, Österreich, marion.gamsjaeger@bhs.at.
Wiener Medizinische Wochenschrift (1946)
|January 10, 2015
Summary
Cathepsin K inhibitors like odanacatib show promise for treating osteoporosis by increasing bone density. However, their effectiveness wanes after discontinuation, requiring further research for sustained bone health.
Area of Science:
- Biochemistry
- Pharmacology
- Bone Biology
Context:
- Cathepsin K is a cysteine protease crucial for collagen type I degradation.
- Its specificity to osteoclasts makes it a target for osteoporosis drug development.
- Previous inhibitors faced challenges due to side effects and limited specificity.
Purpose:
- To review the development of cathepsin K inhibitors.
- To highlight the progress and challenges in developing selective inhibitors.
- To discuss the clinical efficacy and limitations of odanacatib.
Summary:
- Odanacatib (ODN) and ONO-5334 are specific cathepsin K inhibitors that have advanced to clinical trials.
- Odanacatib increases bone mineral density and reduces bone resorption markers in postmenopausal women.
- A resolution-of-effect is observed upon treatment discontinuation, with bone resorption increasing and bone mineral density decreasing.
Impact:
- Odanacatib demonstrates clinical efficacy and safety in improving bone mineral density.
- The resolution-of-effect necessitates further investigation for long-term osteoporosis management.
- Ongoing phase III trials aim to confirm fracture prevention in postmenopausal women with osteoporosis.
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