Compartment-specific skeletal involvement in systemic sclerosis characterized by peripheral QCT and serum osteoimmune mediators: a case-control study

Abstract Systemic sclerosis (SSc) is associated with increased bone fragility, yet early, compartment-specific alterations and their osteoimmunological correlates remain incompletely characterized. This study aimed to assess bone status in SSc using dual X-ray absorptiometry (DXA) complemented by peripheral quantitative computed tomography (pQCT), and to evaluate their associations with a targeted osteoimmunological biomarker panel and clinical risk scores. This prospective cross-sectional study included 40 women with SSc (disease duration ≤ 7 years from diagnosis) and 45 non-immune female controls, frequency-matched by age. Bone status was assessed by DXA (lumbar spine, femoral neck) and distal radius pQCT. Serum levels of routine bone and mineral metabolism markers, alongside a targeted panel of osteoimmunological mediators (OPG, OPN, PDGF-BB, ACP5, RANKL, TNF-α, IL-6, IL-1β, DKK-1) using multiplex immunoassay were measured. FRAX scores were calculated to contextualize clinical fracture risk. With broadly comparable DXA-defined bone status, pQCT revealed significantly lower trabecular volumetric bone mineral density (vBMD) in SSc, while total and cortical+subcortical vBMD were comparable. Routine biochemical markers showed substantial overlap between groups, whereas SSc patients exhibited a distinct osteoimmune profile with significantly elevated OPG, ACP5, RANKL, PDGF-BB, IL-6, IL-1β, DKK-1, and RANKL/OPG after FDR correction. Exploratory biomarker–bone associations did not remain significant after correction for multiple testing. In women with relatively early SSc, pQCT identified compartment-specific differences, particularly within the trabecular compartment, despite comparable DXA-defined bone status. A distinct osteoimmunological biomarker profile was also observed in SSc, providing complementary information on disease-related skeletal alterations, while specific biomarker–bone associations require further confirmation.