Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

Authors:
Mohammad S Khorasani
Mohammad S Khorasani
University of California-Davis Medical Center
Sindi Diko
Sindi Diko
University of California-Davis Medical Center
Allison W Hsia
Allison W Hsia
University of California-Davis Medical Center
Matthew J Anderson
Matthew J Anderson
Saint Joseph's University
Philadelphia | United States
Damian C Genetos
Damian C Genetos
School of Veterinary Medicine
Madison | United States
Prof. Dominik R Haudenschild, Ph.D.
Prof. Dominik R Haudenschild, Ph.D.
University of California Davis Medical Center
Professor
Arthritis Research
Sacramento, CA | United States
Blaine A Christiansen
Blaine A Christiansen
Washington University in St. Louis

Arthritis Res Ther 2015 Feb 16;17:30. Epub 2015 Feb 16.

Department of Orthopaedic Surgery, University of California-Davis Medical Center, 4635 2nd Ave, Suite 2000, Sacramento, CA, 95817, USA.

Introduction: Previous studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury.

Methods: Non-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption.

Results: μCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points.

Conclusions: High-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted.

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http://dx.doi.org/10.1186/s13075-015-0546-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355375PMC

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February 2015
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