Osteoarthritis (OA) is a complex disease that affects bony and cartilaginous joint structures. Progression of OA is associated with cartilage deterioration, sclerosis of the subchondral bone and osteophyte formation. The goal of this study was to investigate whether treatment with antiresorptive (zolendronate) or anabolic therapy (PTH) benefits healing of the articular cartilage in the medial meniscal tear (MMT) model of OA. MMT surgery was performed on male Lewis rats to induce OA. Biomarkers of bone and cartilage metabolism were evaluated in the serum. A dynamic weight bearing (DWB) system was utilised to measure functional capacity of the musculoskeletal system. 3-point bending was used to assess femoral strength. Micro-CT was used to evaluate bone geometry and cartilage morphology. Histomorphometry and histology was used to assess joint morphology. DWB data showed a distinctive difference in weight bearing capacity between sham and MMT rats regardless of treatment. Mechanical testing showed clear differences in cortical bone strength between sham and MMT rats. Contrast mCT and histology data demonstrated degradation of articular cartilage in MMT rats regardless of treatment. Dynamic bone histomorphometry showed increased subchondral bone formation and osteophyte formation in all MMT rats regardless of the treatment paradigm. Results indicate clear insufficiency in the weight bearing capacity of an operated leg. The under-loading of the operated leg caused by pain and mechanical damage to the articular cartilage led to bone loss and weaker cortical bone. Similar degree of cartilage degradation, osteopetrosis and osteophyte formation was seen in all MMT rats. There was no clear benefit of antiresorptive or anabolic bone therapy to the healing process of articular cartilage.
Disclosure: All authors are employed by Pfizer.