Qian Wen, Schmidt Roman, Turner Joseph A, Bare Sue P, Lappe Joan M, Recker Robert R, Akhter Mohammed P
Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588-0526, United States of America.
Osteoporosis Research Center, Creighton University School of Medicine, Omaha, NE 68178, United States of America.
Bone Rep. 2022 Jul 16;17:101604. doi: 10.1016/j.bonr.2022.101604. eCollection 2022 Dec.
The goal of this study is to investigate the causes of osteoporosis-related skeletal fragility in postmenopausal women. We hypothesize that bone fragility in these individuals is largely due to mineral, and/or intrinsic material properties in the osteocyte lacunar/peri-lacunar regions of bone tissue. Innovative measurements with nanoscale resolution, including scanning electron microscope (SEM), an atomic force microscope that is integrated with infrared spectroscopy (AFM-IR), and nanoindentation, were used to characterize osteocyte lacunar and peri-lacunar properties in bone biopsies from fracturing (Cases) and matched (Age, BMD), non-fracturing (Controls) postmenopausal healthy women. In the peri-lacunar space, the nanoindentation results show that the modulus and hardness of the Controls are lower than the Cases. The AFM-IR results conclusively show that the mineral matrix, maturity (peak) (except in outer/far regions in Controls) were greater in Controls than in Cases. Furthermore, these results indicate that while mineral-to-matrix area ratio tend to be greater, the mineral maturity and crystallinity peak ratio "near" lacunae is greater than at regions "far" or more distance from lacunae in the Controls only. Due to the heterogeneity of bone structure, additional measurements are needed to provide more convincing evidence of altered lacunar characteristics and changes in the peri-lacunar bone as mechanisms related to postmenopausal women and fragility. Such findings would motivate new osteocyte-targeted treatments to reduce fragility fracture risks in these groups.
本研究的目的是调查绝经后女性骨质疏松相关骨骼脆性的原因。我们假设这些个体的骨骼脆性很大程度上是由于骨组织骨细胞腔隙/腔隙周围区域的矿物质和/或内在材料特性。采用具有纳米级分辨率的创新测量方法,包括扫描电子显微镜(SEM)、与红外光谱集成的原子力显微镜(AFM-IR)和纳米压痕,来表征骨折(病例组)和匹配的(年龄、骨密度)未骨折(对照组)绝经后健康女性骨活检中骨细胞腔隙和腔隙周围的特性。在腔隙周围空间,纳米压痕结果表明,对照组的模量和硬度低于病例组。AFM-IR结果确凿地表明,对照组的矿物质基质、成熟度(峰值)(对照组外部/远处区域除外)高于病例组。此外,这些结果表明,虽然矿物质与基质面积比往往更大,但仅在对照组中,“靠近”腔隙处的矿物质成熟度和结晶度峰值比“远离”或距离腔隙更远区域处的更大。由于骨结构的异质性,需要进行额外的测量,以提供更有说服力的证据,证明腔隙特征的改变以及腔隙周围骨的变化是绝经后女性和脆性相关的机制。这些发现将推动针对骨细胞的新治疗方法,以降低这些人群脆性骨折的风险。