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 72337 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 (greater than or equal to 3000 µg/d of retinol equivalents [RE]) had a significantly elevated relative risk (RR) of hip fracture (RR, 1.48; 95% confidence interval [CI], 1.05-2.07; P for trend =.003) compared with women in the lowest quintile of intake (<1250 g/d of RE). This increased risk was attributable primarily to retinol (RR, 1.89; 95% CI, 1.33-2.68; P for trend <.001 comparing 2000 µg/d vs <500 g/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% CI, 0.90-1.66; P for trend=.10 comparing greater than or equal to 6300 mug/d vs <2550 g/d). Women currently taking a specific vitamin A supplement had a nonsignificant 40% increased risk of hip fracture (RR, 1.40; 95% CI, 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% CI, 1.05-2.74; P for trend =.05 comparing greater than or equal to 1000 mug/d vs <400 g/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.