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 [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.