Serum Retinoids and β-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 ␤-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 incident hip and other fractures in a large prospective study of British women over the age of 75 years (n ‫ס‬ 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 multivariate 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 ‫ס‬ 0.132) There was a tendency for increased serum retinol to predict benefit rather than harm in terms of BMD (r ‫ס‬ 0.09, p ‫ס‬ 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 ‫ס‬ 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.

The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone

“…These studies have yielded a range of different results with some identifying an association between poor bone health and either low serum retinol (42)(43)(44)(45) or excess vitamin A (4-10, 46), or no difference between study groups (47)(48)(49)(50)(51)(52)(53)(54)(55)(56). For a detailed review see Conaway et al (57).…”

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

“…Studies have also reported an association between high intake of vitamin A and reduced bone mineral density (BMD) (2,5,6). However, several studies have also failed to establish a relationship between serum concentrations of retinol, vitamin A supplementation, and bone density (7)(8)(9)(10)(11).…”

Alternative Therapy through Nutrients and Nutraceuticals

“…Lower serum lycopene, cryptoxanthin, and beta-carotene concentrations have been associated with lower BMD [59,60]. In other studies, foods containing higher amounts of carotenoids have been associated with higher BMD [61,62]. In one study, higher total carotenoids and lycopene intakes were associated with reduced fracture incidence in women and men [63].…”