Serum Retinoids and β-Carotene as Predictors of Hip and Other Fractures in Elderly Women†

There is debate about the possible deleterious effect of excessive vitamin A exposure on fracture risk. In this nested case control study in older women (312 cases and 934 controls), serum retinol, retinyl palmitate, and -carotene were not associated with fracture risk, and there was no evidence of excess risk with multivitamin or cod liver oil supplementation. Introduction: Recent studies have suggested that higher vitamin A intake may account for a component of fracture risk within the general population and that supplemental vitamin A may be harmful even within recommended limits. No studies have examined the relationship between biochemical retinol status and fracture in older women. Materials and Methods: We examined serum retinol, retinyl palmitate, and -carotene as predictors of inci- dent hip and other fractures in a large prospective study of British women over the age of 75 years (n 2606, 312 incident osteoporotic fractures, 92 incident hip fractures; mean follow-up duration, 3.7 years). Fasting blood samples (9:00-11:00 a.m.) were collected at baseline. Using a case-control design (three controls per case), serum retinol, retinyl palmitate, and -carotene were assessed as univariate predictors of incident osteoporotic fracture or hip fracture. Baseline BMD at the total hip, age, 25(OH)D, serum Crosslaps, bone-specific alkaline phosphatase, weight, height, and smoking were considered as covariates in a multivari- ate model. Results: Serum retinol, retinyl palmitate, and -carotene were not significant univariate predictors of either hip fracture or any fracture (all p > 0.05; Cox proportional hazards regression). For all osteoporotic fractures, the hazard ratio (HR) was 0.92 (95% CI, 0.81-1.05) per 1 SD increase in serum retinol. Risk of any osteoporotic fracture was slightly less in the highest quartile of serum retinol compared with the lowest quartile (HR, 0.85; 95% CI, 0.69-1.05; p 0.132) There was a tendency for increased serum retinol to predict benefit rather than harm in terms of BMD (r 0.09, p 0.002). Multivitamin or cod liver oil supplementation was associated with a significantly lower risk of any fracture (HR, 0.76; 95% CI, 0.60-0.96; p 0.021). In multivariate analysis, only age, total hip BMD, and weight were associated with fracture risk (p < 0.05). Conclusions: We found no evidence to support any skeletal harm associated with increased serum indices of retinol exposure or modest retinol supplementation in this population. J Bone Miner Res 2005;20:913-920. Published online on January 24, 2005; doi: 10.1359/JBMR.050112