Inflammatory Biomarkers Predicting Osteoporosis in Autoimmune and Chronic Inflammatory Diseases: A Systematic Review

Abstract

Chronic autoimmune and inflammatory diseases (e.g. rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], inflammatory bowel disease [IBD], ankylosing spondylitis [AS], psoriasis) are frequently accompanied by systemic bone loss and osteoporosis [1,5,6,7,8,10,11]. Pro-inflammatory cytokines (IL-6, TNF-α, etc.) can drive RANKL-mediated osteoclastogenesis[2]. The utility of circulating inflammatory biomarkers (e.g. CRP, IL-6, TNF-α) as predictors of low bone mineral density (BMD) in these diseases is unclear. We performed a systematic review to identify primary human studies linking inflammatory marker levels to osteoporosis or low BMD in patients with autoimmune/inflammatory conditions. We followed PRISMA 2020 guidelines[3] and searched PubMed, Scopus, Web of Science, and other databases through 2025. Inclusion criteria encompassed observational human studies (cohort, case-control, cross-sectional) assessing associations between inflammatory biomarkers (CRP, IL-6, TNF-α, etc.) and BMD or osteoporosis in autoimmune/chronic inflammatory disorders. We excluded reviews, editorials, case reports, non-human studies, and studies without relevant bone outcomes. Two reviewers independently screened records, extracted data (population details, disease, biomarkers, BMD results), and assessed study quality (using JBI checklists[4]). Data were synthesized qualitatively. The search identified ~900 records; after deduplication and screening, nine studies met inclusion (representing RA, SLE, AS, IBD, and psoriasis/PsA). These included studies with sample sizes ranging ~40–141 patients. In RA (three studies), higher IL-6 levels were inversely correlated with lumbar spine and femoral neck BMD[5]. In SLE (one study), elevated CRP and lupus nephritis were linked to lower BMD[6]. In AS (one study), higher CRP and disease activity were associated with greater BMD loss[7]. In Crohn’s disease (one longitudinal cohort), persistently elevated CRP predicted lack of improvement in BMD over time[8]. Overall, inflammatory markers – especially IL-6 and CRP – tended to be higher in patients with lower BMD. Multiple studies suggest that systemic inflammatory activity (reflected by IL-6, CRP, etc.) accompanies bone loss in autoimmune diseases. While heterogeneity and limited sample sizes preclude definitive conclusions, these findings support the concept that inflammatory biomarker levels may help identify patients at risk for osteoporosis. Larger, longitudinal studies are needed to confirm these associations and guide clinical use of biomarkers for bone health monitoring.