title: Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women.
abstract: 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.
  
  
  BACKGROUND
  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.
  
  
  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.
authors.affiliation: Human Nutrition Unit, Division of Clinical Sciences (North), University of Sheffield, United Kingdom. m.e.barker@sheffield.ac.uk
authors.forename: Margo E
authors.initials: ME
authors.lastname: Barker
authors.forename: Eugene
authors.initials: E
authors.lastname: McCloskey
authors.forename: Shikha
authors.initials: S
authors.lastname: Saha
authors.forename: Fatma
authors.initials: F
authors.lastname: Gossiel
authors.forename: Diane
authors.initials: D
authors.lastname: Charlesworth
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Powers
authors.forename: Aubrey
authors.initials: A
authors.lastname: Blumsohn
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001827:Body Height; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000201:enzymology; D016022:Case-Control Studies; D019587:Dietary Supplements; D004224:Diterpenes; D005260:Female; D006620:Hip Fractures / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D015999:Multivariate Analysis; D010024:Osteoporosis / Q000097:blood / Q000175:diagnosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012176:Retinoids / Q000097:blood*; D000084562:Retinyl Esters; D012307:Risk Factors; D013997:Time Factors; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry; D019207:beta Carotene / Q000097:blood*
chemical_list: D004224:Diterpenes; D012176:Retinoids; D000084562:Retinyl Esters; D019207:beta Carotene; D014801:Vitamin A; C014794:retinol palmitate; D000469:Alkaline Phosphatase