Coffee consumption and caffeine intake in relation to risk of fractures: a systematic review and dose-response meta-analysis of observational studies

Background Conflicting reports are available about the association of coffee or caffeine intake and risk of fracture. We performed the current updated systematic review and dose-response meta-analysis of coffee consumption and caffeine intake and risk of fracture to quantify this association.Materials and methods PubMed/Medline, ISI Web of Science, and Scopus, Cochrane database were searched up to July 2021. Random-effects model or fixed-effects model was used to pool the study-specific effect sizes (ESs) and 95% confidence intervals (CIs). Dose-response relationship was examined using linear and non-linear dose–response analyses. The certainty of evidence was assessed using NutriGrade tool.Results Out of 22 eligible studies included in the meta-analysis, 15 had cohort and 7 had case-control design. We found no significant association between coffee consumption and risk of fracture, either based on pooling cohort (RR: 0.99; 95% CI: 0.88, 1.12; I2 = 71.4%, Pheterogeneity < 0.01) or case-control studies (OR: 1.13; 95% CI: 0.87, 1.46; I2 = 49.0%, Pheterogeneity=0.08). In the subgroup analysis of cohort studies, we observed that higher coffee intake was inversely associated with risk of fracture in men (RR: 0.85; 95% CI: 0.76 to 0.94). In addition, a positive association was seen between coffee consumption and risk of fracture in studies with less than 12 years of follow-up (RR: 1.14; 95% CI: 1.02 to 1.27). With regard to caffeine intake, a statistically significant positive association was seen with risk of fracture (RR: 1.15; 95% CI, 1.08 to 1.23; I2=26.6%, n = 8). In the dose-response analysis, we found that each additional 100 mg caffeine intake was marginally associated with 2% greater risk of fracture (RR: 1.02; 95% CI: 1 to 1.05; I2= 70.3%, n = 6).Conclusion High coffee consumption was protectively associated with risk of fracture in men, while caffeine intake was positive associated with risk.