Engdahl Cecilia, Erlandsson Malin C, Hallström Magnus, Deminger Anna, Forsblad-d'Elia Helena
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Arthritis Res Ther. 2025 May 30;27(1):117. doi: 10.1186/s13075-025-03578-9.
Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton and entheses, leading to pathological spinal bone formation and systemic bone loss. Treatments with tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) have shown efficacy in reducing inflammation and potentially impacting bone remodeling in r-axSpA. Osteoclasts, crucial for bone resorption, are derived from the monocytic cell lineage and regulated by proinflammatory cytokines. This study aimed to evaluate the osteoclast development capacity from peripheral blood monocytes in patients with r-axSpA with different treatment strategies and compare it to controls.
This study included 28 patients with long-standing r-axSpA receiving various treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and NSAIDs, as well as 16 blood-donor controls. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score (ASDAS). CD14 + monocytes were isolated from blood samples and differentiated into osteoclasts in vitro by stimulation with three different conditions: (I) macrophage colony-stimulating factor (M-CSF), (II) M-CSF and receptor activator of nuclear factor-κβ (RANKL), and (III) M-CSF, RANKL, and tumor necrosis factor-alpha (TNF). Osteoclast and osteoclast precursor formation were assessed using tartrate-resistant acid phosphatase (TRAP) staining, and TRAP5b concentration in supernatants was measured by ELISA.
The frequency of CD14 + monocytes was similar in patients with r-axSpA and controls, but the capacity to develop osteoclasts and osteoclast precursors was significantly decreased in the r-axSpA patients. Stratification of the patients based on treatment with or without biological DMARDs (bDMARDs) revealed no significant differences in ASDAS or frequency of CD14 + monocytes. Notably, only r-axSpA patients receiving bDMARDs exhibited a reduced ability to develop osteoclasts and osteoclast precursors compared to those not on bDMARDs and controls. Lower Trap5b concentrations in supernatants corroborated these findings.
Our study demonstrates that patients with r-axSpA exhibit a reduced capacity for osteoclast formation from CD14 + monocytes isolated from peripheral blood. The process was modulated by treatment with bDMARDs, which might explain the previously shown sparing effect of bDMARDs on bone mineral density in r-axSpA.
影像学轴向性脊柱关节炎（r-axSpA）是一种慢性炎症性疾病，主要影响中轴骨骼和附着点，导致病理性脊柱骨形成和全身性骨质流失。肿瘤坏死因子抑制剂（TNFi）和白细胞介素-17抑制剂（IL-17i）治疗已显示出在减轻r-axSpA炎症以及潜在影响骨重塑方面的疗效。破骨细胞对骨吸收至关重要，来源于单核细胞谱系并受促炎细胞因子调节。本研究旨在评估不同治疗策略的r-axSpA患者外周血单核细胞的破骨细胞发育能力，并与对照组进行比较。
本研究纳入28例长期r-axSpA患者，接受包括改善病情抗风湿药（DMARDs）和非甾体抗炎药（NSAIDs）在内的各种治疗，以及16名献血者作为对照。使用强直性脊柱炎疾病活动评分（ASDAS）评估疾病活动度。从血样中分离出CD14+单核细胞，并通过三种不同条件刺激在体外分化为破骨细胞：（I）巨噬细胞集落刺激因子（M-CSF），（II）M-CSF和核因子κβ受体激活剂（RANKL），以及（III）M-CSF、RANKL和肿瘤坏死因子-α（TNF）。使用抗酒石酸酸性磷酸酶（TRAP）染色评估破骨细胞和破骨细胞前体的形成，并通过酶联免疫吸附测定（ELISA）测量上清液中TRAP5b的浓度。
r-axSpA患者和对照组中CD14+单核细胞的频率相似，但r-axSpA患者中破骨细胞和破骨细胞前体的发育能力显著降低。根据是否接受生物DMARDs（bDMARDs）治疗对患者进行分层，结果显示ASDAS或CD14+单核细胞频率无显著差异。值得注意的是，与未接受bDMARDs治疗的患者和对照组相比，仅接受bDMARDs治疗的r-axSpA患者破骨细胞和破骨细胞前体的发育能力降低。上清液中较低的Trap5b浓度证实了这些发现。
我们的研究表明，r-axSpA患者从外周血分离的CD14+单核细胞形成破骨细胞的能力降低。该过程受bDMARDs治疗的调节，这可能解释了先前显示的bDMARDs对r-axSpA骨密度的保护作用。
