Antiresorptive therapy conserves some periarticular bone and ligament mechanical properties after anterior cruciate ligament disruption in the rabbit knee
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The purpose of this study was to assess, in an osteoarthritic (OA) model, whether bisphosphonate (BP) antiresorptive therapy altered periarticular bone and bone-ligament biomechanics and OA progression. We surgically transected the anterior cruciate ligament (ACLX) in two groups of rabbits; the first group was dosed with BP (risedronate, 0.01 mg/kg s.c. daily for 6 wk), the second group remained untreated, and a third group of normal (unoperated) control rabbits was also evaluated. We measured distal femoral bone mineral density (BMD, Dual Energy X-ray Absorptiometry [DEXA]), medial collateral ligament (MCL) laxity, and bone mechanical function (bone cores mechanically tested in compression). These measures were related to cartilage/joint gross morphology, histology, and measures of vascular volume (gelatin-dye perfusion) for evidence of inflammatory angiogenesis and early OA. BMD by DEXA in 6 wk ACLX animals was 18% less than normal controls (p<0.05). In contrast, BP dosing conserved periarticular BMD; risedronate-treated rabbits had distal femoral BMD only 5% less and not significantly different than normal controls. When the same bone cores were compressed to failure, both ACLX and BP-dosed animals were significantly weaker than normal controls (p<0.05). However, the bone energy to failure and elastic modulus of BP-dosed animals was conserved and not significantly different from normal controls 6 wk after ACLX. Blocking bone resorption with BP also resulted in a significantly improved bone-ligament structural complex. MCL-complex laxity was significantly less in BP-dosed animals (1.2 times that of normal controls) compared to untreated ACLX animals (1.7 times that of normal controls; p<0.05). Blocking bone resorption with risedronate did not suppress osteophytosis and inflammatory angiogenesis, which were significantly increased in the periarticular bone of both untreated and BP treated ACLX animals. Thus, administering BP immediately after ACL loss conserved some periarticular bone and MCL-complex properties in an early OA model.
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