Panahifar Arash, Cooper David M L, Doschak Michael R
Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
J Orthop Res. 2015 Nov;33(11):1655-62. doi: 10.1002/jor.22937. Epub 2015 Jun 3.
The study objective was to visualize regions of bone that undergo pathological mineralization and/or remodeling during pathogenesis of osteoarthritis, by employing non-radioactive strontium as a dynamic tracer of bone turnover. Post traumatic osteoarthritis was surgically induced in skeletally mature rats, followed by in vivo micro-CT imaging for 12 weeks to assess bone micro-structural changes. Rats either received strontium ranelate daily for the entire course of study or only last 10 days before euthanization. Distribution of strontium in bone was assessed in two and three dimensions, using electron probe micro-analysis (EPMA) and synchrotron dual energy K-edge subtraction micro-CT (SRμCT), respectively. Considerable early formation of osteophytes around the collateral ligament attachments and margins of articulating surfaces were observed, followed by subchondral sclerosis at the later stages. Accordingly, strontium was heavily incorporated by mineralizing osteophytes at 4, 8, and 12 weeks post-surgery, whereas subchondral bone only incorporated strontium between weeks 8-12.This study showed low dose stable strontium can effectively serve as a dynamic tracer of bone turnover to study pathological bone micro-structural changes, at resolution higher than nuclear medicine. Co-administration of strontium during therapeutic drug intervention may show enormous utility in assessing the efficacy of those compounds upon adaptive bone physiology.
本研究的目的是通过使用非放射性锶作为骨转换的动态示踪剂，可视化骨关节炎发病过程中发生病理性矿化和/或重塑的骨区域。在骨骼成熟的大鼠中通过手术诱导创伤后骨关节炎，然后进行12周的体内微型计算机断层扫描（micro-CT）成像以评估骨微结构变化。大鼠在整个研究过程中每天接受雷奈酸锶，或者仅在安乐死前的最后10天接受。分别使用电子探针微分析（EPMA）和同步加速器双能K边减法微型计算机断层扫描（SRμCT）在二维和三维上评估锶在骨中的分布。观察到在侧副韧带附着处和关节表面边缘周围有大量早期骨赘形成，随后在后期出现软骨下硬化。因此，在手术后4周、8周和12周，矿化的骨赘大量摄取锶，而软骨下骨仅在第8至12周摄取锶。本研究表明，低剂量稳定锶可以有效地作为骨转换的动态示踪剂，以研究病理性骨微结构变化，其分辨率高于核医学。在治疗药物干预期间联合使用锶可能在评估这些化合物对适应性骨生理学的疗效方面显示出巨大的效用。
