Impact of Anti-Resorptive Treatment on Bones Recovering From Disuse

Bisphosphonates (BP), drugs that inhibit bone resorption, are used to minimize bone loss in long-duration spaceflight, extended bed rest, and acute spinal cord injury; however, the long term impact of BP use on recovery of bone after disuse is not well understood. This experiment tests the hypothesis that the BP zoledronic acid (ZOL) will protect against loss of bone mass during 28 d hindlimb unloading (HU) while diminishing the ability of cancellous bone formation rate (BFR) to recover following HU. Male Sprague Dawley rats (6 mo) were assigned to aging control (AC), HU, and HU+ZOL groups and subjected to 28 d HU, then to 56 d weight-bearing recovery (REC). Rats were given 2 fluorescent labels 7 days apart to measure BFR in the final week of REC. Histomorphometric analyses of the proximal tibia and distal femur revealed that cancellous BFR was lower in ZOL+HU versus AC both immediately after HU (-96.6%) and after the recovery period (-99.9%) (p<0.05). However, quantitative computed tomography measures of cancellous volumetric bone mineral density (CN-vBMD) at the proximal tibia revealed that CN-vBMD was higher in ZOL+HU versus AC after HU (+120.0%) and after the recovery period (+125.5%) (p