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Background: Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease affecting the axial skeleton and entheses, leading to pathological spinal bone formation and systemic bone loss related to inflammation. Treatment with tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) can mitigate inflammation and influence bone mineral density (BMD) in r-axSpA. Osteoclasts, a cell derived from monocytic lineage and regulated by proinflammatory cytokines, play a key role in bone resorption. Objectives: To investigate the osteoclast development capacity of monocytes in peripheral blood in patients with r-axSpA, particularly those on biological treatment. We examined patients on biological therapy, those without, and age- and sex-matched blood-donor controls. Methods: We included 28 well-characterized patients with long-standing r-axSpA with various medical treatments, including biological and conventional disease-modifying anti-rheumatic drugs (DMARDs) and NSAIDs in the Long-term Outcome Ankylosing Spondylitis (LOAS) cohort in Gothenburg. Disease activity was assessed using Ankylosing Spondylitis Disease Activity Score (ASDAS). In comparison to the LOAS patient, we included 16 matched controls. CD14+ purified cells (monocytes) from blood samples were used for in vitro osteoclast differentiation by stimulating the cells with I; macrophage colony-stimulating factor (MCSF), II; MCSF and receptor activator of nuclear factor-κβ (RANKL) or III; MSCF, RANKL, and tumor necrosis factor-alpha (TNFα) for 3 + 2 days. Osteoclasts and osteoclast precursors were quantified using tartrate-resistant acid phosphatase (Trap) staining, and Trap5b concentration in the supernatant was measured by ELISA. Results: Patients with r-axSpA (mean age of 63 years, range 43-85, 61% men) had varied medical treatments, including NSAIDs (29%), conventional DMARDs (15%), and biological DMARDs (bDMARDs) (46% -TNFi 36% and IL-17i 10%). While r-axSpA patients and controls had a similar frequency of CD14+ monocytes, the ability to develop osteoclasts and osteoclast precursors was decreased in r-axSpA patients. Patients with r-axSpA were further stratified into those on bDMARDs treatment or without. There were no differences in ASDAS or CD14+ monocytes dependent on treatment stratification. However, only the r-axSpA patients on bDMARDs had a reduced ability to develop osteoclasts and osteoclast precursors compared to patients without bDMARDs and controls (Figure 1). These results were confirmed with reduced Trap5b concentration in supernatants, a marker specific for osteoclast development, in r-axSpA patients compared to the controls. Conclusion: Our findings align with prior studies, suggesting that patients with r-axSpA treated with bDMARDs may experience increased bone mineral density, potentially linked to reduced osteoclast differentiation from monocytes in peripheral blood. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.
Engdahl et al. (Sat,) studied this question.