Vitamin A intake and hip fractures among postmenopausal women

Context: Ingestion of toxic amounts of vitamin A affects bone remodeling and can have adverse skeletal effects in animals. The possibility has been raised that long-term high vitamin A intake could contribute to fracture risk in humans. Objective: To assess the relationship between high vitamin A intake from foods and supplements and risk of hip fracture among postmenopausal women. Design: Prospective analysis begun in 1980 with 18 years of follow-up within the Nurses' Health Study. Setting: General community of registered nurses within 11 US states. Participants: A total of 72 337 postmenopausal women aged 34 to 77 years. Main Outcome Measures: Incident hip fractures resulting from low or moderate trauma, analyzed by quintiles of vitamin A intake and by use of multivitamins and vitamin A supplements, assessed at baseline and updated during follow-up. Results: From 1980 to 1998, 603 incident hip fractures resulting from low or moderate trauma were identified. After controlling for confounding factors, women in the highest quintile of total vitamin A intake (≥3000 μg/d of retinol equivalents [RE]) had a significantly elevated relative risk (RR) of hip fracture (RR, 1.48; 95% confidence interval [Cl], 1.05-2.07; P for trend =.003) compared with women in the lowest quintile of intake (<1250 μg/d of RE). This increased risk was attributable primarily to retinol (RR, 1.89; 95% Cl, 1.33-2.68; P for trend ≤.001 comparing ≥2000 μg/d vs <500 μg/d). The association of high retinol intake with hip fracture was attenuated among women using postmenopausal estrogens. Beta carotene did not contribute significantly to fracture risk (RR, 1.22; 95% Cl, 0.90-1.66; P for trend =.10 comparing ≥6300 μg/d vs <2550 μg/d). Women currently taking a specific vitamin A supplement had a nonsignificant 40% increased risk of hip fracture (RR, 1.40; 95% Cl, 0.99-1.99) compared with those not taking that supplement, and, among women not taking supplemental vitamin A, retinol from food was significantly associated with fracture risk (RR, 1.69; 95% Cl, 1.05-2.74; P for trend=.05 comparing ≥1000 μg/d vs <400 μg/d). Conclusions: Long-term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women. The amounts of retinol in fortified foods and vitamin supplements may need to be reassessed.