Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, NY, USA; Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Bone. 2021 Apr;145:115848. doi: 10.1016/j.bone.2021.115848. Epub 2021 Jan 14.
The ability of bone to resist fracture is dependent on the composite nature of its mineral and organic matrix content. Teriparatide (TPTD) and zoledronic acid (ZOL) are approved anabolic and antiresorptive therapies, respectively, to reduce fracture risk in women with postmenopausal osteoporosis. In the SHOTZ study, postmenopausal women with osteoporosis were treated with TPTD (20 μg daily, subcutaneous) or ZOL (5 mg/year, intravenous infusion) for 24 months. Iliac crest biopsies were obtained at 6 months and again at 24 months from approximately one third of the original study cohort. To investigate the early effects of these two drugs on the quality of newly formed bone, we used vibrational spectroscopic techniques to analyze tetracycline-labelled transiliac biopsies obtained from participants at the 6-month time point. Raman spectra were acquired at forming trabecular and intra-cortical surfaces (identified by fluorescent double labels), to determine mineral, organic matrix, glycosaminoglycan, and tissue water content, as well as mineral maturity/crystallinity at three specific tissue ages (1-5, 15, and ≥25 days). Fourier transformed infrared microspectroscopy was used to determine pyridinoline/divalent collagen cross-link ratios. At 6 months, treatment with TPTD versus ZOL resulted in lower mineral and higher organic matrix content, increased tissue water content, and lower mineral/matrix, mineral maturity/crystallinity, glycosaminoglycan content, and pyridinoline/divalent enzymatic collagen cross-link ratio. Our results suggest that TPTD and ZOL have differential effects on material properties of newly formed bone at individual remodeling sites, highlighting their different mechanisms of action.
骨抵抗骨折的能力取决于其矿物质和有机基质含量的复合性质。特立帕肽（TPTD）和唑来膦酸（ZOL）分别是被批准的促合成代谢和抗吸收治疗药物，用于降低绝经后骨质疏松症女性的骨折风险。在 SHOTZ 研究中，绝经后骨质疏松症女性接受 TPTD（每日 20μg，皮下）或 ZOL（每年 5mg，静脉输注）治疗 24 个月。大约三分之一的原始研究队列在 6 个月和 24 个月时获得了髂嵴活检。为了研究这两种药物对新形成骨质量的早期影响，我们使用振动光谱技术分析了来自 6 个月时参与者的四环素标记的跨髂嵴活检。拉曼光谱在形成的小梁和皮质内表面（通过荧光双标记识别）处采集，以确定矿物质、有机基质、糖胺聚糖和组织水含量，以及三个特定组织年龄（1-5、15 和≥25 天）的矿物质成熟度/结晶度。傅里叶变换红外微光谱用于确定吡啶啉/二价胶原交联比。在 6 个月时，与 ZOL 相比，TPTD 治疗导致矿物质含量降低，有机基质含量增加，组织水含量增加，矿物质/基质、矿物质成熟度/结晶度、糖胺聚糖含量和吡啶啉/二价酶胶原交联比降低。我们的结果表明，TPTD 和 ZOL 对个体重塑部位新形成骨的材料特性具有不同的影响，突出了它们不同的作用机制。
