类风湿性关节炎(RA),自身免疫性炎症性疾病,结果持续性滑膜炎伴有严重的骨和软骨破坏。在RA患者中通常使用双膦酸盐(BP)来减少骨破坏和治疗骨质疏松症。然而,BP,尤其是在高剂量下,与颌骨坏死(ONJ)有关。这里,利用以前发表的ONJ动物模型,我们正在探索RA和ONJ发病率和严重程度之间的相互作用.DBA1/J小鼠分为四组:对照组,唑来膦酸(ZA),胶原诱导性关节炎(CIA),还有CIA-ZA.用媒介物或ZA预处理动物。在弗氏佐剂中乳化的牛胶原蛋白II被注射以诱发关节炎(CIA),并在下颌磨牙牙冠上钻孔以诱发根尖周病。载体或ZA治疗持续8周。通过显微CT(µCT)和上颌骨和下颌骨的组织学检查测量ONJ指数。关节炎的发展是通过对爪肿胀的视觉评分来评估的,以及指间和膝关节的µCT和组织学。对照和CIA小鼠的上颌骨和下颌骨显示骨丢失,牙周膜(PDL)间隙扩大,laminadura损失,皮质变薄。ZA阻止了ZA和CIA-ZA组的这些变化。在对照和CIA小鼠中,上皮到肺泡峰的距离增加。在ZA和CIA-ZA动物中保留了该距离。ZA和CIA-ZA中存在空的骨细胞腔隙和骨坏死区域,但在CIA-ZA动物中更广泛,表明更严重的ONJ。CIA和CIA-ZA组出现严重的脚掌和膝盖关节炎。CIA小鼠的指间和膝关节显示出晚期骨破坏,皮质侵蚀和小梁骨丢失,和ZA治疗减少了这些影响。重要的是,CIA-ZA小鼠关节炎症区域附近未发现骨坏死。我们的数据表明,在ZA治疗的CIA小鼠中,ONJ负担更为明显,RA可能是ONJ发展的危险因素。©2016美国骨骼和矿物质研究协会。
Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (
ONJ). Here, utilizing previously published
ONJ animal models, we are exploring interactions between RA and
ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen-induced arthritis (CIA), and CIA-ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freund\'s adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks.
ONJ indices were measured by micro-CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for
ONJ development. © 2016 American Society for Bone and Mineral Research.