Department of Orthopedic Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Acta Pharmacol Sin. 2013 Mar;34(3):387-92. doi: 10.1038/aps.2012.170. Epub 2013 Feb 4.
To investigate the long-term effects of alendronate (Aln), a widely used oral bisphosphonate, on fracture healing and bone remodeling in ovariectomized rats.
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 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).
The 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.
In 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.
研究广泛应用的口服双膦酸盐阿仑膦酸钠（Aln）对去卵巢大鼠骨折愈合和骨重建的长期影响。
成年雌性 SD 大鼠行卵巢切除术，术后 12 周行双侧股骨切开术。从卵巢切除术后第 2 天开始，动物被分为 3 组，分别给予阿仑膦酸钠（3 mg·kg(-1)·d(-1)，po）治疗 28 周（Aln/Aln）、阿仑膦酸钠治疗 12 周和生理盐水治疗 16 周（Aln/Saline）或生理盐水治疗 28 周（Saline/Saline）。在骨折后 6 周和 16 周，通过 X 射线放射照相检查骨折痂，进行生物力学测试和组织学分析。用四环素和钙黄绿素标记骨痂，以评估矿化沉积率（MAR）。
骨折后 6 周时，2 个阿仑膦酸钠治疗组的骨折线不太明显，所有 3 组在骨折后 16 周时均消失。骨折后 6 周和 16 周时，Aln/Aln 组骨痂的大小和股骨的放射密度在 3 组中最高。在失效时的最大负荷和能量吸收方面也观察到了类似的结果。然而，阿仑膦酸钠的治疗延迟了骨痂的软骨内骨化，并显著增加了总矢状截面积、骨痂面积百分比和骨痂厚度，同时降低了骨折后 6 周和 16 周的 MAR。
在去卵巢大鼠模型中，阿仑膦酸钠有利于骨痂的机械性能，但通过抑制编织骨向板层骨的重塑来延迟骨痂重塑。
