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Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A Intake and Hip Fractures Among Postmenopausal Women. JAMA. 2002;287(1):47–54. doi:10.1001/jama.287.1.47
Author Affiliations: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (Drs Feskanich, Willett, and Colditz), and Departments of Nutrition (Dr Willett) and Epidemiology (Drs Willett and Colditz), Harvard School of Public Health, Boston, Mass; and Roche Vitamins Inc, Human Nutrition Research, Parsipanny, NJ (Dr Singh).
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
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 [CI], 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% CI, 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% CI, 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% 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
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.
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