Harris Dominique, Garrett Kate, Uppuganti Sasidhar, Creecy Amy, Nyman Jeffry S
Meharry Medical College, 1005 Dr. DB Todd Jr. Blvd., Nashville, TN 37208, USA.
Department of Orthopaedic Surgery, Vanderbilt University Medical Center, 1215 21(st) Ave. S., Suite 4200, Nashville, TN 37232, USA.
Bone. 2020 Aug;137:115438. doi: 10.1016/j.bone.2020.115438. Epub 2020 May 29.
The likelihood of experiencing an osteoporotic fracture of one or more vertebral bodies increases with age, and this increase is not solely due to sex steroid deficiency. For the purpose of assessing the effectiveness of novel therapeutic strategies in the prevention of vertebral fractures among the elderly, we hypothesized that the BALB/c mouse model of aging phenocopies the age-related decrease in human VB strength. To test this hypothesis, we assessed the age-related changes in trabecular architecture of the L6 VB, with respect to those in the distal femur metaphysis, between 6-mo. (young adulthood, n = 20/sex) and 20-mo. of age (old age, n = 18/sex) and then determined how well the architectural characteristics, volumetric bone mineral density (vBMD), and predicted failure force from μCT-derived finite element analysis (μFEA) with linear elastic failure criteria explained the age-related variance in VB strength, which was the ultimate force during quasi-static loading of the VB in compression. While there was a pronounced age-related deterioration in trabecular architecture in the distal femur metaphysis of female and male BALB/c mice, the decrease in trabecular bone volume fraction and trabecular number between 6-mo. and 20-mo. of age occurred in male mice, but not in female mice. As such, the VB strength was lower with age in males only. Nonetheless, BV/TV and volumetric bone mineral density (vBMD) positively correlated with the ultimate compressive force of the L6 VB for both females and males. Whether using a fixed homogeneous distribution of tissue modulus (E = 18 GPa) or a heterogeneous distribution of E based on a positive relationship with TMD, the predicted failure force of the VB was not independent of age, thereby suggesting linear μFEA may not be a suitable replacement for mechanical-based measurements of strength with respect to age-related changes. Overall, the BALB/c mouse model of aging mimics the age-related in decline in human VB strength when comparing 6-mo. and 20-mo. old male mice. The decrease in VB strength in female mice may occur over a different age range.
一个或多个椎体发生骨质疏松性骨折的可能性会随着年龄增长而增加，且这种增加并非仅仅归因于性类固醇缺乏。为了评估新型治疗策略在预防老年人椎体骨折方面的有效性，我们假设BALB/c衰老小鼠模型可模拟人类椎体强度随年龄增长而下降的情况。为验证这一假设，我们评估了6个月大（成年早期，每组雌雄各20只）和20个月大（老年期，每组雌雄各18只）的BALB/c小鼠L6椎体小梁结构相对于股骨远端干骺端小梁结构的年龄相关变化，然后确定小梁结构特征、体积骨密度（vBMD）以及基于线性弹性失效标准的μCT衍生有限元分析（μFEA）预测的破坏载荷，在解释椎体强度的年龄相关差异方面效果如何，椎体强度是椎体在准静态压缩载荷下的极限载荷。虽然雌性和雄性BALB/c小鼠股骨远端干骺端的小梁结构均出现了明显的与年龄相关的退化，但6个月至20个月龄期间，小梁骨体积分数和小梁数量的减少仅发生在雄性小鼠中，雌性小鼠未出现。因此，仅在雄性小鼠中，椎体强度随年龄降低。尽管如此，雌性和雄性小鼠的骨体积分数（BV/TV）和体积骨密度（vBMD）均与L6椎体的极限压缩力呈正相关。无论使用固定的均匀组织模量分布（E = 18 GPa）还是基于与骨小梁矿物质密度（TMD）的正相关关系的E的非均匀分布，椎体的预测破坏载荷均与年龄相关，这表明就年龄相关变化而言，线性μFEA可能无法完全替代基于力学的强度测量。总体而言，在比较6个月和20个月大的雄性小鼠时，BALB/c衰老小鼠模型可模拟人类椎体强度随年龄下降的情况。雌性小鼠椎体强度的下降可能发生在不同的年龄范围内。
