Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.
Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.
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丙膦酸盐对小鼠前交叉韧带破裂引起的创伤后骨关节炎的影响。
DOI：
10.1186/s13075-015-0546-0
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发表时间：
2015-02-16
影响因子：
4.9
通讯作者：
Christiansen BA
中科院分区：
文献类型：
--
作者：
Khorasani MS;Diko S;Hsia AW;Anderson MJ;Genetos DC;Haudenschild DR;Christiansen BA
以往在骨关节炎动物模型中的研究表明，阿仑膦酸钠（ALN）具有抗骨吸收和软骨保护作用，并可减少骨赘形成。然而，这些研究使用了非生理损伤方法，并且没有研究软骨退变之前骨快速重塑的早期时间点。本研究利用小鼠膝关节损伤的非侵入性模型来研究ALN治疗对损伤后软骨下骨变化、关节软骨退变和骨赘形成的影响。通过胫骨压缩过载或假损伤对总共90只小鼠进行非侵入性膝关节损伤。小鼠每周两次皮下注射低剂量ALN（40 μg/kg/剂）、高剂量ALN（1，000 μg/kg/剂）或溶媒，从损伤后立即开始，直至第7、14或56天处死。使用显微计算机断层扫描（μCT）对股骨骨骺的松质骨、软骨下皮质骨和骨赘体积进行定量。在所有时间点进行全关节组织学检查，以分析关节软骨和关节退行性变。处死时采集血液，分析血清中骨形成和骨吸收的生物标志物。μCT分析显示，损伤后7天和14天股骨骺的骨小梁明显丢失，高剂量ALN治疗可有效防止这种情况。高剂量ALN治疗还能够减少损伤后56天的软骨下骨增厚，并且能够在损伤后14天部分保留关节软骨。然而，ALN治疗不能减少损伤后56天的骨赘形成，也不能在这个时间点防止关节软骨和关节退化。血清生物标志物分析显示，在伤后7天和14天骨吸收增加，在任何时间点骨形成没有变化。高剂量ALN治疗能够预防非侵入性膝关节损伤后的早期骨小梁丢失和软骨退变，但不能减轻长期关节退变。这些数据有助于了解双膦酸盐对骨关节炎发展的影响，并可能支持使用抗吸收药物来预防损伤后的关节退行性变，尽管需要进一步研究。
Previous studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury. Non-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption. μCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points. High-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted.
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影响因子：
3.7
作者：
Funck-Brentano T;Lin H;Hay E;Ah Kioon MD;Schiltz C;Hannouche D;Nizard R;Lioté F;Orcel P;de Vernejoul MC;Cohen-Solal ME
通讯作者：
Cohen-Solal ME
影响因子：
7
作者：
Mohan, G.;Perilli, E.;Kuliwaba, J. S.
通讯作者：
Kuliwaba, J. S.
影响因子：
27.4
作者：
Kadri, Abderrahim;Funck-Brentano, Thomas;Cohen-Solal, Martine E.
通讯作者：
Cohen-Solal, Martine E.
影响因子：
2.8
作者：
Newberry, WN;Zukosky, DK;Haut, RC
通讯作者：
Haut, RC
影响因子：
7
作者：
Christiansen, B. A.;Anderson, M. J.;Haudenschild, D. R.
通讯作者：
Haudenschild, D. R.