• Ling-jie Fu, Ting-ting Tang, Yong-qiang Hao, and Ke-rong Dai.
• Department of Orthopedic Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
• Acta Pharmacol. Sin. 2013 Mar 1; 34 (3): 387-92.

AimTo investigate the long-term effects of alendronate (Aln), a widely used oral bisphosphonate, on fracture healing and bone remodeling in ovariectomized rats.MethodsAdult 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 Aln (3 mg·kg(-1)·d(-1), po) for 28 weeks (Aln/Aln), Aln for 12 weeks and saline for 16 weeks (Aln/Saline) or saline for 28 weeks (Saline/Saline). At 6 and 16 weeks post-fracture, the fracture calluses were examined with X-ray radiography, and biomechanical testing and histological analysis were performed. The calluses were labeled with tetracycline and calcein to evaluate the mineral apposition rate (MAR).ResultsThe fracture line was less distinct in the 2 Aln-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 Aln/Aln 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. However, the treatment with Aln 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.ConclusionIn the ovariectomized rat model, Aln is beneficial for the mechanical properties of the callus, but delays callus remodeling by suppressing the remodeling of woven bone into lamellar bone.

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