Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats

Aim： To investigate the long-term effects of alendronate （AIn）, a widely used oral bisphosphonate, on fracture healing and bone remod- eling in ovariectomized rats. Methods： Adult female SD rats underwent ovariectomy, and then bilateral femoral osteotomy at 12 weeks post-ovariectomy. From d 2 post-ovariectomy, the animals were divided into 3 groups, and treated with AIn （3 mg·kg^1·d^-1, pc） for 28 weeks （AIn/AIn）, AIn for 12 weeks and saline for 16 weeks （AIn/Saline） or saline for 28 weeks （Saline/Saline）. At 6 and 16 weeks post-fracture, the fracture cal- luses were examined with X-ray radiography, and biomechanical testing and histological analysis were performed. The calluses were labeled with tetracyc Results： The fracture ne and calcein to eva ine was less distinct uate the mineral apposition rate （MAR） n the 2 AIn-treated groups at 6 weeks post-fracture, and disappeared in all the 3 groups at 16 weeks post-fracture. The size of the callus and radiographic density of the femora in the AIn/AIn group were the highest among the 3 groups at 6 and 16 weeks post-fracture. Similar results were observed in the ultimate load at failure and energy absorption. How- ever, the treatment with AIn delayed endochondral ossification of the callus, and significantly increased the total sagittal-sectional area percentage callus area and callus thickness, and decreased the MAR at 6 and 16 weeks post-fracture. Conclusion： In the ovariectomized rat model, AIn is beneficial for the mechanical properties of the callus, but delays callus remodeling by suppressing the remodeling of woven bone into lamellar bone.