Lories R J U, Derese I, Luyten F P
Division of Rheumatology, Department of Musculoskeletal Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
Rheumatology (Oxford). 2008 May;47(5):605-8. doi: 10.1093/rheumatology/ken082. Epub 2008 Mar 11.
The relationship between inflammation, destruction and new tissue formation leading to ankylosis, determines the severity and prognosis of patients with SpA. Recent data in mice and men suggest that new cartilage and bone formation and subsequent ankylosis are uncoupled from chronic inflammation. These data challenge the hypothesis that inflammation and tissue damage trigger an excessive repair response in SpA. We tested whether inhibition of bone erosion by targeting osteoclasts, would prevent or influence joint ankylosis in a mouse model.
Male DBA/1 mice from different litters were caged together at the age of 8 weeks. Treatment with zoledronic acid (ZA) (100 ng/g) or placebo was started at the age of 10 weeks and administered every 2 weeks. Clinical incidence and severity of arthritis were evaluated twice a week until the age of 26 weeks. At this point, bone density measurements were performed, mice were sacrificed and severity of arthritis was evaluated by histology.
Treatment with ZA did not affect incidence or clinical severity of arthritis in male DBA/1 mice. ZA treatment significantly increased bone mineral density and content as demonstrated by dual X-ray densitometry and peripheral quantitative CT. However, the treatment did not affect histomorphological appearance of arthritis or ankylosis.
These data suggest that bone erosion at the enthesis does not necessarily precede entheseal ankylosis. Therefore, these observations further support the concept that inflammation and new tissue formation in SpA are at least partially uncoupled events and may be different therapeutic targets.
炎症、破坏与导致关节强直的新组织形成之间的关系，决定了脊柱关节炎（SpA）患者的病情严重程度和预后。近期在小鼠和人类中的数据表明，新的软骨和骨形成以及随后的关节强直与慢性炎症无关。这些数据对炎症和组织损伤引发SpA中过度修复反应的假说提出了挑战。我们测试了通过靶向破骨细胞抑制骨侵蚀是否能预防或影响小鼠模型中的关节强直。
来自不同窝的雄性DBA/1小鼠在8周龄时饲养在一起。在10周龄时开始用唑来膦酸（ZA）（100 ng/g）或安慰剂进行治疗，每2周给药一次。每周评估两次关节炎的临床发病率和严重程度，直至26周龄。此时，进行骨密度测量，处死小鼠，并通过组织学评估关节炎的严重程度。
ZA治疗对雄性DBA/1小鼠关节炎的发病率或临床严重程度没有影响。双能X线骨密度仪和外周定量CT显示，ZA治疗显著提高了骨矿物质密度和含量。然而，该治疗并未影响关节炎或关节强直的组织形态学表现。
这些数据表明，附着点处的骨侵蚀不一定先于附着点关节强直。因此，这些观察结果进一步支持了SpA中的炎症和新组织形成至少部分是不相关事件且可能是不同治疗靶点的概念。
