Hao Y, Wang X, Wang L, Lu Y, Mao Z, Ge S, Dai K
Department of Orthopaedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Department of Orthopaedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Bone. 2015 Dec;81:702-711. doi: 10.1016/j.bone.2015.09.018. Epub 2015 Oct 3.
MINI-ABSTRACT: In this study, we demonstrated that the use of zoledronic acid does not impair fracture healing, but results in superior callus size and resistance at the fracture site, which could be the consequence of a lower rate of bone turnover due to its anti-catabolic effect.
To investigate the effect of inhibition of bone remodeling by the bisphosphonate, zoledronic acid, on callus properties in an osteoporotic rat model of fracture healing.
Ovariectomized (OVX) rats were randomly divided into four treatment groups (n=24 per group): saline control (CNT); and three systemic zoledronic acid-injected groups (0.1mg/kg), administered 1 day (ZOLD1), 1 week (ZOLW1), and 2 weeks (ZOLW2) after fracture. Rats were killed at either 6 or 12 weeks postoperatively. Postmortem analyses included radiography, microcomputed tomography, histology, histomorphometry, biomechanical tests, and nanoindentation tests.
Treatment with zoledronic acid led to a significant increase in trabecular bone volume within the callus, as well as in callus resistance, compared to those in the saline control rats; delayed administration (ZOLW2) reduced intrinsic material properties, including ultimate stress and elastic modulus, and microarchitecture parameters, including bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and connectivity density (Conn.D), compared with ZOLD1 at 12 weeks after surgery. OVX had a negative effect on the progression of endochondral ossification at 6 weeks. Zoledronic acid administration at an early stage following fracture may bind to early callus, and thus not affect subsequent callus formation and endochondral ossification, while delayed administration (ZOLW2) mildly suppresses bony callus remodeling.
The superior results obtained with zoledronic acid (ZOLD1, ZOLW1, and ZOLW2) compared to CNT in terms of callus size and resistance could be the consequence of a lower rate of bone turnover at the fracture site due to the anti-catabolic effect of zoledronic acid. Mild suppression of callus remodeling by delayed administration did not impair the initial phase of the fracture healing process.
在本研究中，我们证明唑来膦酸的使用不会损害骨折愈合，反而会使骨折部位的骨痂尺寸更大且更具抗力，这可能是其抗分解代谢作用导致骨转换率降低的结果。
在骨质疏松性骨折愈合大鼠模型中，研究双膦酸盐唑来膦酸抑制骨重塑对骨痂特性的影响。
将去卵巢（OVX）大鼠随机分为四个治疗组（每组n = 24）：生理盐水对照组（CNT）；以及三个全身注射唑来膦酸的组（0.1mg/kg），分别在骨折后1天（ZOLD1）、1周（ZOLW1）和2周（ZOLW2）给药。术后6周或12周处死大鼠。死后分析包括X线摄影、微型计算机断层扫描、组织学、组织形态计量学、生物力学测试和纳米压痕测试。
与生理盐水对照大鼠相比，唑来膦酸治疗导致骨痂内小梁骨体积以及骨痂抗力显著增加；延迟给药（ZOLW2）与术后12周的ZOLD1相比，降低了包括极限应力和弹性模量在内的内在材料特性以及包括骨体积/总体积（BV/TV）、小梁厚度（Tb.Th）和连通性密度（Conn.D）在内的微结构参数。OVX在6周时对软骨内成骨的进展有负面影响。骨折后早期给予唑来膦酸可能会与早期骨痂结合，从而不影响随后的骨痂形成和软骨内成骨，而延迟给药（ZOLW2）会轻度抑制骨痂重塑。
与CNT相比，唑来膦酸（ZOLD1、ZOLW1和ZOLW2）在骨痂尺寸和抗力方面取得的更好结果可能是唑来膦酸的抗分解代谢作用导致骨折部位骨转换率降低的结果。延迟给药对骨痂重塑的轻度抑制并未损害骨折愈合过程的初始阶段。
