No adverse effects of clodronate on fracture healing in rats

Clodronate was administered daily 28 days before and after an experimental tibial fracture in 35 male rats, and the effect on fracture healing and posttraumatic bone loss was studied. 5 groups were tested. The clodronate/clodronate group received clodronate in daily doses of 10 mg/ kg body weight for 28 days before being subjected to a standardized fracture of the right tibia, and during the fracture healing period of 28 days. The clodronate/ saline group received clodronate before fracture and saline during the healing period. The saline/ clodronate group received saline before and clodronate after fracture. The saline/saline group received saline only, while the control group served as unfractured, untreated controls. After 28 days of fracture healing, the tibias were evaluated with dual energy x-ray absorptiometry, and tested mechanically in a 3-point ventral bending test. Bone mineral content and bone mineral density were approximately 30% higher in the groups receiving clodronate during the experiment, compared to the untreated groups. The weight and cross-sectional area of the fracture callus were equal in all groups. Whether clodronate was administered before the fracture, after the fracture or both, did not affect the bone mineral. Ultimate bending moment, energy absorption, stiffness and deflection were not significantly different between the groups. Our findings suggest that clodronate increases bone mineral both when given before and after a tibial shaft fracture, without affecting fracture healing at 28 days.