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

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Take home message

Managing levels of inflammation in the body may be an important factor for preventing bone loss and risk of fractures post menopause.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

Hypoestrogenism accelerates bone loss in females during the menopausal transition. Chronic inflammation and increased circulating inflammatory markers may be additional mediators and risk factors for osteoporotic fractures. This study aimed to investigate the relationship between inflammatory mediators and bone outcomes in postmenopausal women.

Methods

This study was a cross-sectional analysis of baseline data from a 12-month RCT investigating dietary intake of prunes for bone health. It included N=183 healthy postmenopausal women aged 55-75 years with bone mineral density (BMD) T-scores of between 0.00 and -3.0 in the lumbar spine, total hip and/or femoral neck sites, as measured by dual-energy X-ray absorptiometry (DEXA). Bone strength and geometry were also assessed using peripheral quantitative computed tomography (pQCT).

Measurements

Serum markers for bone turnover; procollagen type 1 N-terminal propeptide (P1NP), C-terminal telopeptide.
Inflammatory markers; high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor (TNF) alpha, interleukins (IL) -1β, IL-6, IL-8, monocyte chemoattractant protein (MCP)-1
Physical activity levels
Dietary calcium
Total energy intake
Body mass index (BMI) - participants classified normal-weight, overweight or obese.

Results

N=24 normal range BMD, n=126 osteopenia and n=33 osteoporosis.
Mean levels of inflammatory markers did not differ between women with osteoporosis, osteopenia, and normal BMD (all p>0.05).
Overweight/obese women had higher levels of inflammatory cytokines (p<0.001)
BMD T-scores were higher in women who were overweight/obese (p=<0.001)
IL-1β, IL-6 and IL-8 were negatively correlated with BMD in normal weight women (p<0.05)
A negative correlation was found between hs-CRP and P1NP (p=0.042)
IL-6 and IL-1β were negatively associated with BMD at the lumbar spine (P<0.05)
IL-6 and TNF-alpha may be predictors of total body (P=0.027), lumbar spine (P=0.036) and total hip (P=0.028) BMD, after adjusting for BMI.

Conclusion

This study found an inverse association between inflammatory markers and BMD, bone strength and geometry in postmenopausal women.

Clinical practice applications

Addressing inflammation may be beneficial for managing bone health and preventing bone loss in postmenopausal women.
Obesity may increase inflammatory markers, however, it was correlated with higher BMD in postmenopausal women, potentially due to elevated load and increased oestrogen production from adipose tissue.

Considerations for future research

Larger and longer studies are needed to confirm these results, taking into consideration potential confounding factors such as age, BMI, diet and physical activity levels.
Further studies are needed to investigate anti-inflammatory interventions to protect BMD in postmenopausal women.

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 (=-0.197, =0.042). Plasma IL-1β, IL-6, IL-8, and TNF-α negatively correlated with trabecular bone score at the lumbar spine (all <0.05). In normal-weight women, plasma IL-1β, IL-6, and IL-8 negatively correlated (<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 (=0.078, =0.028). Plasma IL-6 negatively predicted BMD at the total body (=-0.131, =0.027) and lumbar spine (=-0.151, =0.036), whereas plasma TNF-α negatively predicted total hip BMD (=-0.114, =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.