A rat model for testing pharmacologic treatments of pressure-related bone loss

Abstract

Fluid pressure, instability, or particles have been suggested to initiate the process leading to loosening of prosthetic implants. In a rat model where bone resorption is caused by oscillating fluid pressure, the resorptive response seems much stronger than the response that can be induced by particles or instability. Bone resorption is caused by osteoclasts. It has been suggested that the formation of osteoclasts is influenced by tumor necrosis factor-alpha, which can be blocked by etanercept. Osteoclasts can be inactivated with bisphosphonates, which bind to bone and inactivate osteoclasts when the bisphosphonate-containing bone is resorbed. Bone formation can be increased dramatically by intermittent parathyroid hormone treatment, especially at sites with high bone turnover. This might compensate for increased osteoclastic activity. Forty-two rats received a plate implant, by which fluid pressure was applied to a bone surface by compressing a soft tissue membrane. Eight rats were treated with etanercept 0.75 mg/kg/day, six rats were treated with alendronate 205 microg/kg/day, six rats received saline, and six rats were nonpressurized controls. Nine rats received intermittent parathyroid hormone treatment with nine separate controls. The area of bone resorption under the implant was evaluated by histomorphometry. Alendronate-treated rats showed less bone resorption, but etanercept, intermittent parathyroid hormone treatment, or saline did not reduce the fluid pressure-induced bone resorption. This model is a comparatively simple way of testing pharmacologic reduction of local bone resorption in vivo.