Department of Anatomy and Cell Biology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Bone. 2013 Sep;56(1):199-203. doi: 10.1016/j.bone.2013.06.004. Epub 2013 Jun 14.
Atypical femoral fractures, which display characteristics of brittle material failure, have been associated with potent remodeling suppression drugs. Given the millions of individuals treated with this class of drugs it is likely that other factors play a role in these fractures. Some evidence suggests that concomitant use of corticosteroids may contribute to the pathogenesis although data in this area is lacking. The goal of this study was to assess the combined role of bisphosphonates and dexamethasone on bone mechanical properties. Skeletally mature beagle dogs were either untreated controls, or treated with zoledronic acid (ZOL), dexamethasone (DEX), or ZOL + DEX. Zoledronic acid (0.06 mg/kg) was given monthly via IV infusion for 9 months. DEX (5 mg) was administered daily for one week during each of the last three months of the 9 month experiment. Ribs were harvested and assessed for bone geometry, mechanical properties, and remodeling rate (n = 3-6 specimens per group). DEX significantly suppressed intracortical remodeling compared to vehicle controls while both ZOL and the combination of DEX + ZOL nearly abolished intracortical remodeling. ZOL treatment resulted in significantly lower bone toughness, determined from 3-point bending tests, compared to all other treatment groups while the toughness in ZOL + DEX animals was identical to those of untreated controls. These findings suggest that short-courses of dexamethasone not only do not adversely affect toughness in the setting of bisphosphonates, but also actually reverse the adverse effects of its treatment. Understanding the mechanism for this tissue-level effect could lead to novel approaches for reducing the risk of atypical femoral fractures.
非典型股骨骨折表现出脆性材料断裂的特征，与强效的重塑抑制药物有关。鉴于数以百万计的个体接受了这类药物的治疗，其他因素很可能在这些骨折中起作用。一些证据表明，同时使用皮质类固醇可能有助于发病机制，尽管这方面的数据缺乏。本研究的目的是评估双膦酸盐和地塞米松联合应用对骨力学性能的影响。骨骼成熟的比格犬分为未治疗对照组或唑来膦酸（ZOL）、地塞米松（DEX）或 ZOL + DEX 治疗组。唑来膦酸（0.06mg/kg）每月通过 IV 输注给药，共 9 个月。DEX（5mg）在 9 个月实验的最后三个月中的每一周给予一次。采集肋骨并评估骨几何形状、力学性能和重塑率（每组 3-6 个标本）。与载体对照相比，DEX 显著抑制皮质内重塑，而 ZOL 和 DEX + ZOL 联合治疗几乎完全消除皮质内重塑。与所有其他治疗组相比，ZOL 治疗导致 3 点弯曲试验确定的骨韧性显著降低，而 ZOL + DEX 动物的韧性与未治疗对照组相同。这些发现表明，短期使用地塞米松不仅不会在双膦酸盐的情况下对韧性产生不利影响，而且实际上还可以逆转其治疗的不利影响。了解这种组织水平效应的机制可能会为降低非典型股骨骨折的风险提供新的方法。
