Associations Between Inflammatory Mediators and Bone Outcomes in Postmenopausal Women: A Cross-Sectional Analysis of Baseline Data from the Prune Study

Purpose: Hypoestrogenism triggers increased production of inflammatory mediators, which contribute to bone loss during post-menopausal osteoporosis. This study aimed to investigate the association between circulating inflammatory markers and bone outcomes in postmenopausal women.Materials and methods: We conducted a cross-sectional, secondary analysis of baseline data from participants who completed a 12-month randomized controlled trial, The Prune Study (NCT02822378), which included healthy postmenopausal women (n=183, 55-75 years old) with bone mineral density (BMD) T-score between 0.0 and -3.0 at any site. BMD was measured using dual-energy X-ray absorptiometry, and bone geometry and strength were measured using peripheral quantitative computed tomography. Blood was collected at baseline to measure (1) serum biomarkers of bone turnover, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide and (2) inflammatory markers, including serum high-sensitivity C-reactive protein (hs-CRP) and plasma pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1, using enzyme-linked immunosorbent assay. The associations between bone and inflammatory outcomes at baseline were analyzed using correlation and regression analyses.Results: Serum hs-CRP negatively correlated with P1NP (r=-0.197, p=0.042). Plasma IL-1 beta, IL-6, IL-8, and TNF-alpha negatively correlated with trabecular bone score at the lumbar spine (all p<0.05). In normal-weight women, plasma IL-1 beta, IL-6, and IL-8 negatively correlated (p<0.05) with trabecular and cortical bone area, content, and density at various sites in the tibia and radius. Serum hs-CRP positively predicted lumbar spine BMD (8=0.078,p=0.028). Plasma IL-6 negatively predicted BMD at the total body (8=-0.131,p=0.027) and lumbar spine (8=-0.151, p=0.036), whereas plasma TNF-alpha negatively predicted total hip BMD (8=-0.114, p=0.028).Conclusion: At baseline, inflammatory markers were inversely associated with various estimates of bone density, geometry, and strength in postmenopausal women. These findings suggest that inflammatory markers may be an important mediator for postmeno-pausal bone loss.