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

Abstract

Purpose 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.

Associations of HMGB1, sTNFR-1 and NRL with the infectious premature delivery in pregnant women undergoing cervical cerclage

“…As a member of the chemokine family, HMGB1 induces the softening and relaxation of internal cervical ori ce by recruiting the downstream complement or chemokine C3a; low HMGB1 level can recruit the immune cells and promote the proliferation and differentiation of endometrial stromal cells required for normal pregnancy, while high HMGB1 level is associated with pregnancy failure [13][14] . sTNFR-1 is a member of the TNFR family, whose regulatory effects on different TNF-α receptors can enhance the pathological role of in ammatory factors, intensifying their damage to amniotic sac wall cells to increase the risk of premature delivery [15][16] . NLR is a sensitive in ammatory index discovered in current research, which not only indicates the role of neutrophils in infection, but also correlates with the lymphocyte count in the body.…”

A review of mathematical modeling of bone remodeling from a systems biology perspective

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Can Post-Menopausal Osteoporosis Be Prevented by Essential Fatty Acids? [Letter]

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