Barrett Jennifer G, Sample Susannah J, McCarthy Jenna, Kalscheur Vicki L, Muir Peter, Prokuski Laura
Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin--Madison, 2015 Linden Drive, Madison, Wisconsin 53706, USA.
J Orthop Res. 2007 Aug;25(8):1070-7. doi: 10.1002/jor.20395.
Targeted remodeling of fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to cyclic fatigue. The ulnae of 140 rats were cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during fatigue. After fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
针对疲劳损伤骨骼的靶向重塑涉及破骨细胞吸收的激活，随后成骨细胞进行局部骨形成。我们研究了胃肠外阿仑膦酸钠（ALN）对骨骼适应周期性疲劳的影响。对140只大鼠的尺骨进行单侧周期性加载，直至刚度损失40%。我们使用了八个治疗组：（1）基线对照；（2）载体（无菌盐水）和（3）疲劳前的阿仑膦酸钠，无适应（分别为Pre-VEH、Pre-ALN）；（4）载体和（5）适应疲劳期间的阿仑膦酸钠（分别为Post-VEH、Post-ALN）；（6）疲劳前和适应期间的载体（Pre-VEH/Post-VEH）；（7）疲劳前的阿仑膦酸钠和适应期间的载体（Pre-ALN/Post-VEH）；（8）疲劳前和适应期间的阿仑膦酸钠（Pre-ALN/Post-ALN）。每组一半大鼠的骨骼进行力学测试；其余骨骼进行组织学检查。对以下变量进行了量化：骨体积矿物质密度（vBMD）；极限力（F(u)）；刚度（S）；失效功（U）；皮质面积（Ct.Ar）；新编织骨组织面积（Ne.Wo.B.T.Ar）；吸收空间密度（Rs.N/T.Ar）。微裂纹仅在疲劳加载的尺骨中可见。未发现阿仑膦酸钠对vBMD有显著影响。疲劳前用阿仑膦酸钠进行预防性治疗并不能保护尺骨在疲劳期间免受结构降解。疲劳后，通过适应机械性能得以恢复；在此未发现阿仑膦酸钠有显著影响。未发现阿仑膦酸钠对适应性Ne.Wo.B.T.Ar有特异性影响。在疲劳加载的尺骨中，与基线对照相比，载体治疗的适应组中Rs.N/T.Ar增加，但阿仑膦酸钠治疗的适应组中未增加。这些数据表明，在该模型中短期阿仑膦酸钠治疗不能保护骨骼免受疲劳。随着时间的推移，重塑的抑制可能会减少微裂纹修复。
