Jones Michael D, Tran Charles W, Li Guang, Maksymowych Walter P, Zernicke Ronald F, Doschak Michael R
Pharmacy and Pharmaceutical Sciences, University of Alberta, Dentistry/Pharmacy Centre, Edmonton, Alberta, Canada.
Arthritis Rheum. 2010 Sep;62(9):2726-35. doi: 10.1002/art.27595.
To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA).
We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam.
Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury.
Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.
确定抗吸收药物与抗炎药物联合治疗是否能减少与创伤后继发性骨关节炎（OA）进展相关的关节周围骨和软组织适应性改变。
我们使用体内微焦点计算机断层扫描（micro-CT）来绘制骨适应性变化，并使用体内微磁共振成像（micro-MRI）来检查手术诱发的膝关节三联伤后继发性OA大鼠模型中的关节炎症。我们研究了双膦酸盐阿仑膦酸钠和利塞膦酸钠以及非甾体抗炎药（NSAID）美洛昔康的关节保护作用。
与未治疗的动物相比，micro-CT显示用双膦酸盐药物阿仑膦酸钠或利塞膦酸钠或NSAID美洛昔康治疗的膝关节三联伤动物的关节周围小梁骨丢失水平降低。阿仑膦酸钠治疗减少了骨赘形成。虽然利塞膦酸钠单一疗法对骨赘形成没有积极影响，但利塞膦酸钠与美洛昔康联合治疗在一定程度上降低了骨赘严重程度。Micro-MRI显示，手术8周后，未治疗的膝关节三联伤大鼠的骨骺中弥漫性水信号增加，提示存在类似骨髓病变的刺激。相比之下，术后8周，美洛昔康治疗的大鼠与两个双膦酸盐治疗组相比，液体信号显著降低。组织学分析定性证实了两种双膦酸盐治疗的软骨保护作用，与未治疗的膝关节三联伤大鼠相比，降解变化更少。
我们的研究结果表明，在继发性OA早期，双膦酸盐和NSAID药物治疗的特定组合可保留小梁骨量，并减少骨赘性骨适应性改变和类似骨髓病变刺激的影响。如果在初始损伤后早期给药，双膦酸盐和NSAID治疗可能是一种有效的改善病情的药物方案。
