Effect of pamidronate on distraction osteogenesis and fixator-related osteoporosis

Abstract

We examined the effect on bone mineral density (BMD), bone mineral content (BMC) and mechanical properties of a single 1.0 mg/kg dose of the bisphosphonate pamidronate (Novartis), in a distraction osteogenesis model in immature rabbits. Twenty rabbits underwent a tibial osteotomy. Ten rabbits received pamidronate 1.0 mg/kg via ear vein intra-operatively while 10 received saline infusions only. After a 24 h latency, all underwent distraction of 0.375 mm twice daily for 15 days. The animals were culled at 42 days. After culling, the distracted and non-distracted tibiae were examined by quantitative computer tomography (QCT). The volumetric bone mineral density (vBMD, mg/cm 3) in the bone proximal and distal to the regenerate in the operated limb was increased by a mean of 11 and 14%, respectively, compared to controls ( P<0.05). The vBMD of the regenerate bone was increased by a mean of 8% over controls (NS, P=0.17). The bone mineral content (BMC, mg) was increased by 23% (proximal and distal) ( P<0.05) in the bone surrounding the lengthening and there was a 17% trend towards an increase in the regenerate (NS, P=0.3). Four-point bending analysis documented that the load to failure was increased by 32% from 436 to 574 N ( P<0.01) in the pamidronate group. The modulus of elasticity was not different between the control and pamidronate groups ( P=0.3), and in both groups was only approximately one-third of the intact tibiae ( P<0.001). The administration of a single dose of pamidronate can improve the bone mineral density, content and mechanical properties of a bone undergoing distraction osteogenesis.