Scheffler Julia M, Drevinge Christina, Lindholm Catharina, Gjertsson Inger, Lend Kristina, Lund Hetland Merete, Østergaard Mikkel, Uhlig Till, Schrumpf Heiberg Marte, Haavardsholm Espen A, Nurmohamed Michael T, Lampa Jon, Sokka-Isler Tuulikki, Nordström Dan, Hørslev-Petersen Kim, Gudbjornsson Bjorn, Gröndal Gerdur, van Vollenhoven Ronald, Carlsten Hans, Lorentzon Mattias, Hultgård Ekwall Anna-Karin, Rudin Anna, Islander Ulrika
University of Gothenburg, Gothenburg, Sweden.
University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
ACR Open Rheumatol. 2025 Jan;7(1):e11742. doi: 10.1002/acr2.11742. Epub 2024 Oct 16.
The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell-derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA.
Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4 T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT).
HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3Th2 cells (r = -0.38, P = 0.04) and CXCR3Th17 cells (r = -0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing.
MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.
类风湿关节炎（RA）中骨质疏松的高患病率归因于炎症刺激破骨细胞分化，这一过程涉及循环单核细胞和T细胞衍生因子。本研究的目的是评估RA患者循环单核细胞、T细胞亚群与生物性改善病情抗风湿药物（bDMARDs）治疗前后骨特征变化之间的关系。
纳入30例符合美国风湿病学会/欧洲抗风湿病联盟2010标准的未经治疗的早期RA患者。在使用甲氨蝶呤（MTX）联合三种bDMARDs（阿巴西普、托珠单抗或赛妥珠单抗聚乙二醇化制剂）之一治疗前及治疗48周后收集数据。使用临床疾病活动指数、肿胀或压痛关节计数、C反应蛋白水平和红细胞沉降率来测量疾病活动度。通过流式细胞术分析血样中单核细胞和CD4 T细胞亚群的比例。使用高分辨率外周定量计算机断层扫描（HR-pQCT）进行骨密度测定。
HR-pQCT显示皮质骨（P = 0.009）和小梁骨（P = 0.034）骨密度总体下降，尽管一部分患者在治疗48周后未出现骨质流失。总体骨质流失与年龄、体重指数、性别、关节内糖皮质激素注射或基线疾病活动度无关。小梁骨体积分数的降低与基线时循环CXCR3Th2细胞（r = -0.38，P = 0.04）和CXCR3Th17细胞（r = -0.36，P = 0.05）的高比例相关。同样，小梁骨体积分数无降低与基线时调节性T细胞的高比例相关（r = 0.4，P = 0.03）。然而，在校正混杂因素和多重检验后，这些关联并不显著。
MTX联合bDMARDs可有效降低疾病活动度，但仅在一部分RA患者治疗48周后预防骨质流失。循环基线辅助性T细胞和调节性T细胞群体与小梁骨变化的相关性表明这些细胞在早期RA全身骨稳态中可能具有新的作用。
