The Relationship Between Vitamin A and Risk of Fracture: Meta-Analysis of Prospective Studies

Abstract

Osteoporotic fracture is a significant cause of morbidity and mortality and is a challenging global health problem. Previous reports of the relation between vitamin A intake or blood retinol and risk of fracture were inconsistent. We searched Medline and Embase to assess the effects of vitamin A (or retinol or beta-carotene but not vitamin A metabolites) on risk of hip and total fracture. Only prospective studies were included. We pooled data with a random effects meta-analysis with adjusted relative risk (adj.RR) and 95% confidence interval (CI). We used Q statistic and I 2 statistic to assess heterogeneity and Egger's test to assess publication bias. Eight vitamin A (or retinol or beta-carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included. . The risk of total fracture does not differ significantly by level of vitamin A (or retinol) intake or by blood retinol level. Dose-response meta-analysis shows a U-shaped relationship between serum retinol level and hip fracture risk. Our meta-analysis suggests that blood retinol level is a double-edged sword for risk of hip fracture. To avoid the risk of hip fracture caused by too low or too high a level of retinol concentration, we suggest that intake of beta-carotene (a provitamin A), which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake.

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

“…It now seems probable that both low and high serum retinol levels as well as high intake of vitamin A can contribute to poor bone health and skeletal fragility (58).…”

“…A meta-analysis by Wu and colleagues assessed the level of vitamin A intake (in 283,930 participants) or serum retinol levels (in 8725 participants) and the risk of either hip fractures or total body fractures using relative risk estimates based on 95% confidence intervals from 12 prospective studies (58). The conclusion was that high intake of vitamin A and both low and high serum retinol levels were associated with elevated with risk of hip fracture but not total body fractures (58).…”

Retinoid Receptors in Bone and Their Role in Bone Remodeling

“…Table 1 is a summary of individual studies based on either increases, decreases, or no association of fracture risk or bone mineral density (BMD) to increased vitamin A intake or increased vitamin A intake/low vitamin D. The data suggest that increased vitamin A intake/low vitamin D favors a decrease in BMD and an increase in fracture risk (108–110); however, the effect of increased intake of vitamin A alone appears to be less clear, with increases (25, 26, 111–117), decreases (118–121), and no associations (122–128) to fracture risk and BMD reported. In contrast to the individual observations, a recent meta-analysis of prospective studies has suggested that high retinol intake and blood retinol levels have no effect on total fractures, but significantly increase the risk of hip fracture (129). …”

The outcomes of percutaneous kyphoplasty in treatment of the secondary osteoporotic vertebral compression factures: a case-control study

“…The hormone-replacement therapy and parathyroid hormone (PTH) also can increase vertebral bone-mineral density (26). Proper intake of vitamin D, vitamin A, vitamin K, calcium and protein may also improve the bone-mineral density and reduce the risk of fracture (3,(27)(28)(29).…”

“…Osteoporotic fracture is one of the major global burdens of diseases (1)(2)(3). Osteoporotic fractures could occur in hip, vertebrae, and limbs.…”