Bajaj Devendra, Geissler Joseph R, Allen Matthew R, Burr David B, Fritton J C
Department of Orthopaedics, New Jersey Medical School, Rutgers University, 205 S. Orange Avenue, Newark, NJ 07103, USA.
Department of Orthopaedics, New Jersey Medical School, Rutgers University, 205 S. Orange Avenue, Newark, NJ 07103, USA; Department of Biomedical Engineering, New Jersey Institute of Technology, 323 Martin Luther King, Jr. Boulevard, Newark, NJ 07102, USA.
Bone. 2014 Jul;64:57-64. doi: 10.1016/j.bone.2014.03.045. Epub 2014 Apr 1.
Bisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions.
双膦酸盐是治疗骨质疏松症最常用的预防性药物。然而，最近发现长期使用双膦酸盐会导致皮质骨非典型骨折，这些患者出现低能量诱发骨折，其病理生理学尚不清楚。双膦酸盐对皮质骨力学性能的影响仅在简单、单调、准静态加载条件下进行过研究。本研究在低能量情况下组织损伤开始并在明显骨折之前积累的水平上，检测了双膦酸盐处理的皮质骨的循环疲劳特性。对从犬肋骨加工而成的梁（1.5毫米×0.5毫米×10毫米）（每组n = 12）施加生理相关的动态四点弯曲，结果表明机械失效和微观结构特征取决于药物剂量（3组：0、0.2、1.0毫克/千克/天；阿仑膦酸钠[ALN]，给药3年），皮质骨组织弹性模量（加载初始循环）降低了21%（p<0.001），采用应力-寿命方法时，ALN1.0组的疲劳寿命（失效循环次数）降低了3倍以上（p<0.05）。虽然ALN处理不影响骨单位数量，但减少了与骨重塑相关的其他特征，如骨单位大小（-14%；ALN1.0组：10.5±1.8，对照组：12.2±1.6，×10(3) 平方微米；p<0.01）和骨细胞陷窝密度（-20%；ALN1.0组：11.4±3.3，对照组：14.3±3.6，×10(2) 个/平方毫米；p<0.05）。此外，将各组合并后，骨细胞陷窝密度与初始弹性模量成正比（R = 0.54，p<0.01）。这些发现表明，高剂量ALN处理改变了通常对健康皮质骨组织有贡献的结构成分，并导致循环加载条件下力学性能降低。
