Diet-wide association study (DWAS) of hip fracture risk in UK postmenopausal women: a prospective cohort study of 541,887 women with 27,318 incident cases over ~ 20 years.

Previous research on diet and hip fracture risk focused on selected foods and nutrients. We aim to conduct a systematic diet-wide association study of 99 dietary factors. The study population comprised 541,887 postmenopausal women in the Million Women Study. Dietary information was assessed using a validated food frequency questionnaire in 2000-2004, and calibrated using a 24-hour dietary recall. Incident hip fracture was ascertained through linked hospital admission records. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). After an average of 19.7 years of follow-up, 27,318 incident hip fractures occurred. In multivariable-adjusted models, 60 dietary factors were associated with hip fracture risk after multiple testing correction. The top five foods (based on p-value) were: chicken (HR and 95% CI = 0.84, 0.80-0.87 per 20 g/day), vegetables (0.88, 0.85-0.91 per 100 g/day), pasta (0.87, 0.83-0.91 per 20 g/day), chips (1.14, 1.10-1.18 per 25 g/day), and fizzy drinks (1.18, 1.12-1.24 per 50 g/day). The top five nutrients were: protein (0.79, 0.75-0.84 per 15 g/day), zinc (0.81, 0.77-0.86 per 2 mg/day), carotene (0.91, 0.88-0.94 per 1000 µg/day), fibre (0.89, 0.85-0.92 per 5 g/day), and niacin (0.82, 0.77-0.87 per 10 mg/day). The results were consistent across subgroup analyses and in analyses excluding the first five years of follow-up. Many "healthy" foods were associated with lower risk of hip fracture, and "unhealthy" foods with higher risk. Further research is needed to assess whether these associations were causal or reflect overall diet quality or other lifestyle confounding.