Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Osteoarthritis Cartilage. 2012 Jul;20(7):694-702. doi: 10.1016/j.joca.2012.03.021. Epub 2012 Apr 9.
To employ elemental Strontium as a tracer of bone turnover, in the presence (or absence) of the bisphosphonate drug Alendronate, in order to spatially map osteophytogenesis and other bone turnover in rats developing post-traumatic secondary osteoarthritis (PTOA).
PTOA was induced in rats by medial meniscectomy surgery. We utilized in-vivo microfocal computed tomography (CT) to follow bony adaptations in groups for 8 weeks after surgery, either with or without alendronate treatment. Electron probe microanalysis (EPMA) was used to detect Strontium incorporation in mineralizing tissues. Histologic studies were conducted on the same samples using Safranin-O/fast green and Tetrachrome staining of decalcified sections to examine articular cartilage health and osteophyte formation at the sites of elemental Strontium deposition.
EPMA revealed uniform incorporation of Strontium over actively remodeling trabecular surfaces in normal control rats. That pattern was significantly altered after meniscectomy surgery resulting in greater Strontium signal at the developing osteophyte margins. Alendronate treatment inhibited osteophyte development by 40% and 51% quantified by micro-CT volumetric measurements at 4 and 8 weeks after surgery, respectively. Osteophytes in the alendronate group were more cartilaginous in composition [i.e., lower bone mineral density (BMD)] compared to the untreated group. Histological analysis confirmed the osteophyte inhibitory effect of alendronate, and also verified reduced degeneration of the articular cartilage compared to untreated rats.
Our study confirmed that alendronate administration will reduce osteophyte formation in a rat model of post-traumatic osteoarthritis, partially through the inhibition of secondary remodeling of osteophytes. Our study is the first to employ elemental Strontium as a tracer of bone turnover in the pathogenesis of osteoarthritis and to assess the efficacy of bisphosphonate antiresorptive drug interventions on osteophytogenesis.
利用锶元素作为骨转换的示踪剂，在存在（或不存在）双膦酸盐药物阿仑膦酸钠的情况下，对发生创伤后继发性骨关节炎（PTOA）的大鼠的骨赘形成和其他骨转换进行空间定位。
通过内侧半月板切除术手术诱导 PTOA 大鼠模型。我们利用体内微焦点 CT（micro-CT）在手术后 8 周内对各组进行随访，观察是否有阿仑膦酸钠治疗。利用电子探针微分析（EPMA）检测矿化组织中的锶掺入情况。对相同样本进行组织学研究，使用番红 O/快绿和脱钙切片的四色染色，检查关节软骨健康和锶元素沉积部位的骨赘形成。
EPMA 显示，在正常对照组大鼠的活跃重塑小梁表面均匀掺入锶。在半月板切除手术后，这种模式发生了显著改变，导致在新形成的骨赘边缘处出现更大的锶信号。阿仑膦酸钠治疗分别在手术后 4 周和 8 周时通过 micro-CT 体积测量，使骨赘发育减少了 40%和 51%。与未治疗组相比，阿仑膦酸钠组的骨赘在组成上更具软骨样[即，骨矿物质密度（BMD）较低]。组织学分析证实了阿仑膦酸钠对骨赘的抑制作用，并证实与未治疗大鼠相比，关节软骨的退变减少。
我们的研究证实，阿仑膦酸钠给药可减少创伤后骨关节炎大鼠模型中的骨赘形成，部分通过抑制骨赘的继发性重塑。我们的研究首次将锶元素作为骨关节炎发病机制中骨转换的示踪剂，并评估双膦酸盐抗吸收药物干预对骨赘形成的疗效。
