The analysis involved a total of 34,703 predominantly white (99.3%) women with a median age of 61 years. There were 525 incident hip fractures, and a total of 6,502 hip and nonhip fractures. The mean length of follow-up was 9.5 person-years. Slightly over one third of the participants (35%) used supplements containing vitamin A at baseline (n = 12,293). Supplement users were slightly younger, less obese, physically more active, more educated, and less likely to have diabetes compared with nonusers (). They were also more likely to use thyrotropic, sedative, and steroid medications, and estrogen replacement therapy. The energy-adjusted mean intakes of protein, calcium, and vitamin D were higher, whereas the mean caffeine intake was lower among supplement users compared with nonusers. The mean total vitamin A intake was 6,920 IU higher among supplement users compared with nonusers. There were generally similar differences among the subjects grouped by quintiles of total vitamin A intake (extreme quintile results shown in ).
Age-adjusted characteristics of vitamin A supplement users and nonusers, and between the 1st and 5th quintiles of total vitamin A intake, Iowa Women's Health Study, 1986
In the age-adjusted model, vitamin A supplement users had a 17% higher risk of hip fracture compared with nonusers (95% CI, −2% to +39%) (results not shown). The relative risk was similar after adjusting for age, BMI, WHR, diabetes mellitus, physical activity, steroid medication, and estrogen replacement therapy (RR = 1.18, 95% CI, 0.99 to 1.41). Vitamin A supplement use was not associated with risk of all fractures (RR = 1.00, 95% CI, 0.95 to 1.05, after adjusting for age, BMI, education, diabetes mellitus, cirrhosis, and use of sedative, thyrotropic, seizure, and steroid medications). When analyzed according to quantity of vitamin A obtained from supplements, risk of hip fracture was slightly greater than 1.0 for each level of vitamin A from supplement use compared with nonusers (). However, these relative risks were not statistically significant, and a dose-response relationship was not observed. Similarly null results were seen with increasing amounts of retinol intake from supplements for hip fracture and for all fractures ().
Relative risks of hip and all fractures according to supplemental vitamin A and retinol intake versus supplement nonusers, Iowa Women's Health Study, 1986–1997
shows the relative risk of hip and all fractures by quintiles of total vitamin A and retinol intake, with the covariates adjusted for, indicated in footnotes. Other dietary factors such as calcium or vitamin D were not found to be independent risk factors for fracture in the models and were not included. There were no significant dose-response relationships across quintiles of total vitamin A or retinol intake and hip fracture risk. There also was no association between total vitamin A or retinol intake and risk of any fracture. Two supplemental analyses were run (not shown). First, we confirmed that very high levels were not especially risky, as the RR of hip fracture for the highest decile of vitamin A intake compared with the lowest decile was 1.15 (95% CI, 0.76 to 1.76). When cut points ( < 1,250 μg/day [ < 6,250 IU/day], 1,250–1,699 μg/day [6,250–8,499 IU/ day], 1,700–2,249 μg/day [8,500–11,249 IU/day], 2,250–2,999 μg/day [11,250–14,999 IU/day], and ≥3,000 μg/day [≥15,000 IU/day]) from the Nurses' Health Study were used , there still was no association.
Relative risks of hip and all fractures by quintiles of total vitamin A and retinol intake, Iowa Women's Health Study, 1986–1997
Among nonusers of supplements, there also was no association of increasing quintiles of vitamin A or retinol intake from food with the risk of hip fracture (). In fact, women in the highest quintile of retinol intake had 26% fewer hip fractures than those in the first quintile (95% CI, −50% to +8%). Among supplement nonusers, increasing quintiles of food-derived vitamin A were inversely associated with all fracture types (p value for test of trend = 0.01). A similar trend was not observed for increasing quintiles of food-derived retinol, and there was no evidence of an increased risk of any fracture beyond the first quintile of retinol intake. Among supplement users, no effect of food-derived vitamin A or retinol on hip or all fractures was seen as well (results not shown).
Relative risks of hip and all fractures by quintiles of vitamin A and retinol intake from food-only among supplement nonusers, Iowa Women's Health Study, 1986–1997