Effects of bisphosphate treatment and mechanical loading on bone modeling in the rat tibia.

Bisphosphonate treatment has been shown to decrease endosteal bone formation and increase periosteal bone apposition in the rat tibial diaphysis. This study tested the hypothesis that the increase in periosteal apposition is a compensatory attempt to maintain skeletal mass appropriate for the mechanical load. Twenty-four rats were divided into four groups. In two of the groups, one hindlimb in each rat was immobilized with a sling device to increase the mechanical load on the opposite limb. Daily injections of dichloromethylene bisphosphonate (Cl2MBP) were given at 10 mg/kg to one immobilized group and one mobile group. The other two groups were given daily injections of normal saline. Fluorescent bone labels were administered at two-week intervals. All rats were killed after ten weeks of treatment, and calcified tibial cross sections were prepared for fluorescence microscopy. Bone dimensions and periosteal and endosteal apposition rates were calculated. When compared with saline controls, Cl2MBP treatment decreased endosteal apposition rate in all tibias. Periosteal apposition rate was increased with Cl2MBP treatment in all tibias except the unloaded limb of immobilized rats. The Cl2MBP-induced increase in periosteal apposition rate was greatest in loaded limbs and was proportional to the relative amount of body weight supported.