Antiresorptive and Anabolic Bone Therapy Does not Improve Weight Bearing Capacity and Bone Strength in OA Rats

Objective: This manuscript reports the outcomes of medial meniscectomy (MM) surgery on cartilage and cortical bone strength and the reaction of cartilage and bone to intensive treatment with antiresorptive (zoledronate) and anabolic bone (PTH) therapies.Methods: Medial meniscectomy was used to induce OA in male Lewis rats. Therapy with zoledronate and human PTH was initiated immediately after surgery. A dynamic weight-bearing system was deployed to evaluate the weight-bearing capacity. At the end of the 10-week study cartilage pathology was evaluated by contrast μCT imaging and histology. Cortical bone geometry at femoral mid-diaphysis was evaluated by μCT and strength was tested using 3-point bending method.Results: MM surgery caused negative consequences including cartilage deterioration, osteophyte formation, a decrease in weight-bearing capacity and decreased cortical bone strength.Conclusions: Treatment with zoledronate and PTH cannot prevent or correct the deterioration of the hyaline cartilage, osteophyte formation and the mechanical incapacity of the osteoarthritic knee. The partial and prolonged disuse of the osteoarthritic leg caused by the surgery has a deteriorating effect on cortical strength that was not corrected with anabolic or antiresorptive treatment. Our data suggest that early restoration of the mechanical function of the injured knee is a mandatory first step in preventing cartilage deterioration and supporting the recovery of joint structures and that a multitherapeutic approach is warranted to treat various aspects of post-traumatic osteoarthritis.</p