Background/Purpose: Juvenile spondyloarthritis (JSpA) management is hindered by the lack of reliable biomarkers to predict which patients will develop progressive structural changes, such as erosions and ankylosis. Chronic inflammation, driven by cytokines like IL-17 and TNFα, disrupts bone homeostasis by enhancing osteoclast-mediated resorption and compensatory osteoblast-driven deposition, ultimately resulting in bone damage. Bone turnover proteins may serve as potential biomarkers for disease activity and progression in JSpA. In this study, plasma levels of key regulators of bone resorption-including osteopontin (OPN), acid phosphatase 5 (ACP5), and dickkopf-1 (DKK-1)-as well as bone formation markers, such as platelet-derived growth factor-BB (PDGF-BB), and alkaline phosphatase (ALPL), were compared between JSpA patients and healthy controls.

Methods: This cross-sectional, single-center study analyzed plasma samples from 30 systemic medication-naïve JSpA patients who met at least one of the following criteria: (1) International League of Associations for Rheumatology (ILAR) enthesitis-related arthritis (ERA) criteria, or (2) inflammatory sacroiliitis on MRI. Plasma concentrations of 13 bone metabolism–related proteins, along with IL-17, IFN-γ, and TNFα, were measured using the LEGENDPlex multiplex bead-based immunoassay. These levels were compared to previously published reference ranges from healthy controls using the Mann-Whitney test. Plasma concentrations were correlated with other analytes and clinical metadata using Spearman’s Rank Correlation.

Results: Table 1 summarizes the demographic data and plasma protein concentrations. Compared to healthy controls, subjects with JSpA had significantly higher levels of OPN (P < 0.0001), ACP5 (P < 0.0001), and ALPL (P < 0.0001). In contrast, DKK-1 (P < 0.001) and PDGF-BB (P = 0.004) levels were significantly lower in JSpA patients. TNFα was significantly elevated in patients, whereas no significant differences were observed in IL-17 or IFN-γ. Sub analysis reveals no difference between HLA B27 positive and negative subjects. These findings are graphically represented in Figure 1. These proteins had low correlation with clinical Juvenile Arthritis Disease Activity Score (cJADAS10) and inflammatory markers (ESR and CRP), with all r between -0.25 and < 0.25 (Figure 2). OPN, ACP5, ALPL, and DKK-1 had strong, positive correlations with alkaline phosphatase activity

Conclusion: Significant differences in bone metabolism proteins were observed between JSpA patients and healthy controls, suggesting a shift toward bone resorption driven by increased osteoclast activity and disrupted bone homeostasis. Further, the low correlations observed between disease activity measures and inflammatory markers highlight the need for a multimodal approach to assessing activity in axJSpA. Further validation is needed to determine whether bone metabolism proteins could serve as biomarkers of disease progression and potential therapeutic targets.

Patient Characteristics and Comparison of Plasma Protein Concentrations in Juvenile Spondyloarthritis Patients versus Healthy Reference

Juvenile Spondyloarthritis Patients reveal an altered bone metabolism profile

Spearman Rank Correlation Analysis of Bone Metabolism Proteins with Clinical Metadata

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/new-onset-juvenile-spondyloarthritis-is-characterized-by-bone-metabolism-disturbances-with-biomarker-potential/