Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women

J Bone Miner Res. 2005 Jun;20(6):913-20. doi: 10.1359/JBMR.050112. Epub 2005 Jan 24.


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 beta-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 beta-carotene as predictors of incident 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 beta-carotene were assessed as univariate predictors of incident osteoporotic fracture or hip fracture. Baseline BMD at the total hip, age, 25(OH)D, serum beta Crosslaps, bone-specific alkaline phosphatase, weight, height, and smoking were considered as covariates in a multivariate model.

Results: Serum retinol, retinyl palmitate, and beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alkaline Phosphatase / metabolism
  • Body Height
  • Body Weight
  • Bone Density
  • Bone and Bones / enzymology
  • Case-Control Studies
  • Dietary Supplements
  • Diterpenes
  • Female
  • Hip Fractures / blood*
  • Hip Fractures / diagnosis*
  • Humans
  • Multivariate Analysis
  • Osteoporosis / blood
  • Osteoporosis / diagnosis
  • Proportional Hazards Models
  • Regression Analysis
  • Retinoids / blood*
  • Retinyl Esters
  • Risk Factors
  • Time Factors
  • Vitamin A / analogs & derivatives*
  • Vitamin A / blood*
  • Vitamin A / chemistry
  • beta Carotene / blood*


  • Diterpenes
  • Retinoids
  • Retinyl Esters
  • beta Carotene
  • Vitamin A
  • retinol palmitate
  • Alkaline Phosphatase