Effects
of alendronate on post-traumatic osteoarthritis induced by anterior cruciate
ligament rupture in mice.
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].
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.
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.
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.
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?
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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Khorasani, M., Diko, S., Hsia, A., Anderson, M., Genetos, D., Haudenschild, D., & Christiansen, B. (2015). Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice Arthritis Research & Therapy, 17 (1) DOI: 10.1186/s13075-015-0546-0