Uppuganti Sasidhar, Granke Mathilde, Makowski Alexander J, Does Mark D, Nyman Jeffry S
Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States.
Bone. 2016 Feb;83:220-232. doi: 10.1016/j.bone.2015.11.009. Epub 2015 Nov 22.
In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue.
除了随着年龄增长出现的骨量流失外,材料特性也会下降。为了测试针对材料强度和韧性等特性的新疗法或诊断工具,一种老化的临床前模型将很有用,其中骨骼的变化与人类衰老时发生的变化相似。为此,我们假设,与人类骨骼类似,雄性Fischer F344大鼠皮质骨在表观水平的估计韧性和材料强度会随着年龄增长而下降。此外,我们测试了大鼠小梁结构已知的下降是否转化为与年龄相关的椎骨(VB)强度下降,以及非X射线技术是否可以在微米和亚微米长度尺度上量化组织变化。从6个月、12个月和24个月大的大鼠(每个年龄n = 12)身上采集骨骼。尽管随着年龄增长小梁骨有所流失,但各年龄组之间的VB抗压强度相似。同样,随着年龄增长,弯曲时的全骨强度(峰值力)在股骨中保持不变或在桡骨中增加。不过,屈服后韧性(桡骨)和弯曲强度(股骨)会随着年龄增长而下降。12个月和24个月大的大鼠抵抗裂纹萌生的能力实际上比6个月大的大鼠(带缺口股骨)更高,但老化骨骼扩展裂纹的估计功较小。对于股骨干区域,孔隙率随着年龄增长而增加,而结合水则减少。对于桡骨干,非酶促和成熟酶促胶原交联随着年龄增长而增加。对胫骨干中段嵌入横截面的拉曼光谱分析检测到,随着衰老的进展,内外组织的碳酸盐取代均增加。