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High-sensitivity C-reactive protein is an independent risk factor for non-vertebral fractures in women and men: The
Kristoffer Dahl1, Luai Awad Ahmed1, Ragnar Martin Joakimsen2
1Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
Insights
High-sensitivity C-reactive protein (CRP) indicates fracture risk in both men and women, though its association with bone mineral density (BMD) differs by gender. Inflammation impacts fracture risk independently of BMD.
Area of Science:
- Gerontology
- Bone Biology
- Inflammation Research
Background:
- Low-grade inflammation is linked to fractures, but its association with bone mineral density (BMD) and potential gender differences remain unclear.
- High-sensitivity C-reactive protein (CRP) is a marker of systemic inflammation.
Purpose of the Study:
- To investigate high-sensitivity C-reactive protein (CRP) as an independent risk factor for low BMD and non-vertebral fractures in men and women.
- To explore potential gender differences in the association between CRP, BMD, and fracture risk.
Main Methods:
- Cross-sectional and longitudinal study involving 1902 women and 1648 men (55-74 years) from the Tromsø Study.
- Measurement of CRP levels and BMD (total hip, femoral neck); registration of non-vertebral fractures over an average 7.2-year follow-up.
- Statistical analyses included linear regression for BMD and Cox proportional hazards models for fracture prediction.
Main Results:
- CRP was not associated with BMD in women but showed an inverse association in men.
- Elevated CRP levels were associated with an increased risk of non-vertebral fractures in both genders.
- After adjusting for BMD and other risk factors, higher CRP tertiles significantly increased fracture risk in both women (39%) and men (80%).
Conclusions:
- Systemic inflammation, indicated by CRP, is an independent risk factor for non-vertebral fractures in both men and women.
- The relationship between inflammation and bone health differs between genders, with inflammation inversely associated with BMD only in men.
- Biological mechanisms underlying inflammation's impact on fracture risk may differ between genders.
Abstract:
Low-grade inflammation is associated with fractures, while the relationship between inflammation and bone mineral density (BMD) is less clear. Moreover, any gender differences in the sensitivity to inflammation are still poorly elucidated. We therefore tested the hypothesis that high-sensitivity C-reactive protein (CRP) is an independent risk factor for low BMD and non-vertebral fractures, in both genders, and whether there are gender differences in these associations. CRP levels and BMD at the total hip and femoral neck were measured in 1902 women and 1648 men between 55 and 74 years of age, at baseline in the Tromsø Study, Norway, in 2001-2002. Non-vertebral fractures were registered from hospital X-ray archives during an average of 7.2 years follow-up. Linear regression analyses were used for CRP association with BMD and Cox proportional hazards model for fracture prediction by CRP. During 25 595 person-years follow-up, 366 (19%) women and 126 (8%) men suffered a non-vertebral fracture. There was no association between CRP and BMD in women, but an inverse association in men (p=0.001) after adjustment for age and body mass index. Each standard deviation (SD) increase in log-CRP was associated with an increased risk for non-vertebral fracture by 13% in women and 22% in men (hazard ratios (HRs) 1.13, 95% confidence interval (CI) 1.02-1.26, p=0.026 and 1.22, 95% CI=1.00-1.48, p=0.046, respectively). After adjustment for BMD and other risk factors, women with CRP in the upper tertile exhibited 39% higher risk for fracture than those in the lowest tertile of CRP (HR = 1.39, 95% CI = 1.06-1.83, p = 0.017), while men in the upper tertile exhibited 80% higher risk (HR=1.80, 95% CI=1.10-2.94, p=0.019). In summary, CRP was not associated with BMD in women but inversely associated in men, and predicted fractures in both genders. We infer that inflammation influence fracture risk in both women and men, although the biological mechanisms may differ between the genders.
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