Tetracycline use in treating osteoarthritis: a systematic review.

BACKGROUND AND AIMS: The purpose of the review was to synthesize the current literature regarding tetracyclines in the treatment of osteoarthritis. METHODS: Using multiple databases, a systematic review was performed with customized search terms crafted to identify studies examining doxycycline or minocycline in the treatment of osteoarthritis. Results were classified into basic science mechanistic studies, in vivo animal studies, and human clinical trials. A total of 1446 potentially relevant studies were reviewed, and after exclusion criteria were applied, 23 investigations were included in the final analysis. RESULTS: From 12 basic science mechanistic studies, we report on three main mechanisms by which tetracyclines may exert benefit in osteoarthritis progression: matrix metalloproteinase inhibition, immunomodulation, and nitric oxide synthase inhibition. Seven animal studies showed generally encouraging results. Four articles reported human clinical studies, showing mixed results in the treatment of osteoarthritis, potentially related to the choice of patient population, primary outcomes, and timing of treatment. CONCLUSION: Tetracyclines have the potential to benefit osteoarthritis patients via multiple mechanisms. Further study is warranted to examine the optimal dose and timing of tetracycline treatment in osteoarthritis.