Use of a Bisphosphonate (pamidronate) to Modulate Fracture Repair in Ovine Bone

Bisphosphonates influence the morphology and mechanical properties of bones in growing rats, but their effects on fracture repair are not well documented. This study tests the hypothesis that bisphosphonates will modulate the remodelling phase of fracture repair, influencing the mechanical properties of healing bone. The effects of a bisphosphonate (pamidronate, Aredia) on the healing of a 3 mm osteotomy gap in the mid-diaphysis of the tibia, under rigid unilateral external fixation, were evaluated using 2 groups of 6 skeletally mature sheep. The repair process was evaluated weekly for 12 weeks using conventional radiographs, dual photon absorptiometry, and fracture stiffness measurements. The animals were then killed and the torsional stiffness and strength of the tibiae measured. More prolific callus formation, with an associated rise in the rate of bone mineral content, was observed in the treated group. There were no differences in in vivo fracture stiffness or postmortem torsional stiffness between the 2 groups, but torsional strength was greater in the treated group. Callus remodelling was reduced but not arrested in the treated group. Bisphosphonates act to reduce callus remodelling, leading to an increased amount of bridging callus and therefore strength. This study indicates that pamidronate has no adverse effects on the restoration of the mechanical integrity of a long bone after fracture.