• Diane Feskanich, Vishwa Singh, Walter C Willett, and Graham A Colditz.
• Channing Laboratory, 181 Longwood Ave, Boston, MA 02115. diane.feskanich@channing.harvard.edu
• JAMA. 2002 Jan 2;287(1):47-54.

ContextIngestion 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.ObjectiveTo assess the relationship between high vitamin A intake from foods and supplements and risk of hip fracture among postmenopausal women.DesignProspective analysis begun in 1980 with 18 years of follow-up within the Nurses' Health Study.SettingGeneral community of registered nurses within 11 US states.ParticipantsA total of 72 337 postmenopausal women aged 34 to 77 years.Main Outcome MeasuresIncident 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.ResultsFrom 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 microgram/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 microgram/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 microgram/d vs <500 microgram/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 >/=6300 microgram/d vs <2550 microgram/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 >/=1000 microgram/d vs <400 microgram/d).ConclusionsLong-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.

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