Effects of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.
Khorasani MS, Diko S, Hsia AW, Anderson MJ, Genetos DC, Haudenschild DR and Christiansen BA. Arthritis Res and Therapy. 2015. [Epub Ahead of Print].
Take Home Message: In a mouse model, high-dose injections of alendronate delayed joint damage compared with a low-dose or placebo.
Post-traumatic osteoarthritis (PTOA) is a common, long-term consequence of anterior cruciate ligament (ACL) injury. Unfortunately, there is no approved therapy to prevent or slow the onset of PTOA. Bisphosphonates, like alendronate, are typically used to treat osteoporosis but may also be beneficial in delaying PTOA; however, this is not proven. Therefore, Khorasani and colleagues completed a study to better understand the effectiveness of alendronate in mice with or without an ACL rupture. The authors obtained 90 female mice and randomized them into groups based on injury status, study duration (7, 14, or 56 days), and intervention (placebo solution, low-dose alendronate [40 µg/kg/dose], high-dose [1000 µg/kg/dose]). The mice received doses immediately after the injury and then twice weekly. Fifty-four mice experienced a non-invasive ACL rupture by a tibial compression overload. Thirty-six mice had light compression but not enough to induce an ACL injury. Mice were sacrificed at 7, 14, or 56 days post-injury and the authors assessed measures of bone turnover and cartilage damage. The authors found that in all groups at the 56 day post-injury time point, trabecular bone mass decreased, and considerable osteophyte formation was present. However, at 7 and 14 day post-injury the low-dose alendronate group and the placebo group showed trabecular bone loss and cartilage thinning while the high-dose alendronate group showed significantly less trabecular bone loss and cartilage degeneration.
The results of the current study are encouraging because high-dose alendronate slowed the development of PTOA. But, while alendronate delayed degenerative changes it failed to prevent PTOA. The authors acknowledge that there is conflicting evidence surrounding the use of alendronate and therefore more research is needed to understand how this treatment would impact humans. If the treatment is effective in the short-term but not in the long-term then perhaps a better treatment options exist. An important aspect of this study and many other animal studies that evaluate therapies to prevent PTOA was that the therapy was started immediately after the injury. In contrast, we often don’t think about slowing the development of joint damage until months or years after a patient’s knee injury. Perhaps it is time for clinicians and researchers to consider therapies to slow or prevent PTOA at the time of injury. Until a treatment becomes available, clinicians should continue educating their athletes about the long-term implications of their injuries and continue the most effective, evidence-based treatment.
Questions for Discussion: Do you feel your athletes would be interested in a treatment that may buy them time but not prevent joint damage? As the clinician, do you feel a short-term treatment such as this would impact your treatment strategy?
Written by: Kyle Harris
Reviewed by: Jeffrey Driban
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