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C-reactive protein and fracture risk: an updated systematic review and meta-analysis of cohort studies through the use of both frequentist and Bayesian approaches

Osteoporosis International volume 32, pages 425–435 (2021)Cite this article

Abstract

Summary

This systematic review and meta-analysis were conducted on all eligible cohort studies to evaluate the association between high-sensitivity C-reactive protein (hs-CRP) and osteoporotic fracture risk. Both frequentist and Bayesian approaches were employed for the meta-analysis. We found that high tertiles of hs-CRP were significantly associated with increased fracture risk.

Introduction

The association between the inflammatory marker CRP and osteoporotic fracture has remained uncertain. In this study, we conducted a systematic review and meta-analysis to examine the association of serum hs-CRP and fracture risk.

Methods

We performed a systematic literature search of relevant databases, including PubMed, Embase, and MEDLINE publications from January 1950 through April 2020. Three reviewers independently performed the study selection, quality assessment, and data abstraction. Frequentist and Bayesian hierarchical random-effects models were used separately for the analysis. Statistical heterogeneity was assessed using Higgin’s I2 and Cochran’s Q statistic, and publication bias was examined using funnel plots and rank correlation tests.

Results

Fourteen cohort studies that reported t fracture outcomes were eligible for the systematic review. Only ten studies (n = 29,741) qualified for meta-analysis. In the frequentist approach, the RR for fracture in a comparison of the top tertile group to the bottom tertile group of hs-CRP was 1.54 (1.18, 2.01). The estimated risk of fracture remained significant in all sensitivity and subgroup analyses. Higgin’s I2 (30.52%) and Cochran’s Q statistic (p < 0.01) suggested there was moderate heterogeneity for the meta-analysis. In the Bayesian approach, the pooled RR was 1.60 (95% CI (1.07–2.49)), and the probabilities that the high level of hs-CRP increased fracture risk by more than 0%, 10%, and 20% were 99%, 98%, and 93%, respectively.

Conclusion

A high level of hs-CRP is associated with a significantly increased risk of osteoporotic fracture.

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Fig. 1
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Abbreviations

BMD:

Bone mineral density

CI:

Confidence interval

CRP:

C-reactive protein

HR:

Hazard ratio

MOOSE:

Meta-analysis of observational studies in epidemiology

OR:

Odds ratio

PRISMA:

Preferred Reporting Items for Systematic Review and Meta-analyses

RR:

Relative risk

REDCap:

Research Electronic Data Capture

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health; Nevada Institute of Personalized Medicine, College of Sciences, University of Nevada, Las Vegas, Las Vegas, NV, 89154, USA

    H. Mun & Q. Wu

  2. Department of Mathematical Sciences, Nevada Institute of Personalized Medicine, College of Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA

    B. Liu

  3. School of Life Sciences, Nevada Institute of Personalized Medicine, College of Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA

    T. H. A. Pham

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  1. H. Mun
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  2. B. Liu
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  4. Q. Wu
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Correspondence to Q. Wu.

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Mun, H., Liu, B., Pham, T.H.A. et al. C-reactive protein and fracture risk: an updated systematic review and meta-analysis of cohort studies through the use of both frequentist and Bayesian approaches. Osteoporos Int 32, 425–435 (2021). https://doi.org/10.1007/s00198-020-05623-6

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  • DOI: https://doi.org/10.1007/s00198-020-05623-6

Keywords

  • Bayesian meta-analysis
  • C-reactive protein
  • Fracture
  • Meta-analysis
  • Osteoporosis
  • Systematic review

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