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

Abstract

Janhavi J Damani,1 Mary Jane De Souza,2 Nicole CA Strock,2 Kristen J Koltun,2,3 Nancy I Williams,2 Connie Weaver,4 Connie J Rogers5– 7 1The Intercollege Graduate Degree Program in Integrative and Biomedical Physiology, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA; 2Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA; 3Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA; 4Department of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, USA; 5Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA; 6Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, USA; 7Department of Nutritional Sciences, University of Georgia, Athens, GA, USACorrespondence: Connie J Rogers, 280 Dawson Hall, University of Georgia, Athens, GA, 30602, USA, Tel [phone], Email [email protected]: Hypoestrogenism triggers increased production of inflammatory mediators, which contribute to bone loss during postmenopausal 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)-α, interleukin (IL)-1β, 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-1β, IL-6, IL-8, and TNF-α negatively correlated with trabecular bone score at the lumbar spine (all p< 0.05). In normal-weight women, plasma IL-1β, 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 (β=0.078, p=0.028). Plasma IL-6 negatively predicted BMD at the total body (β=– 0.131, p=0.027) and lumbar spine (β=– 0.151, p=0.036), whereas plasma TNF-α negatively predicted total hip BMD (β=– 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 postmenopausal bone loss.Keywords: inflammation, pro-inflammatory cytokines, immunity, osteoporosis, menopause

Keywords

• inflammation
• pro-inflammatory cytokines
• immunity
• osteoporosis
• menopause