Elucidating causal relationships of diet-derived circulating antioxidants and the risk of osteoporosis: A Mendelian randomization study

Abstract

BackgroundOsteoporosis (OP) is typically diagnosed by evaluating bone mineral density (BMD), and it frequently results in fractures. Here, we investigated the causal relationships between diet-derived circulating antioxidants and the risk of OP using Mendelian randomization (MR).MethodsPublished studies were used to identify instrumental variables related to absolute levels of circulating antioxidants like lycopene, retinol, ascorbate, and β-carotene, as well as antioxidant metabolites such as ascorbate, retinol, α-tocopherol, and γ-tocopherol. Outcome variables included BMD (in femoral neck, lumbar spine, forearm, heel, total body, total body (age over 60), total body (age 45–60), total body (age 30–45), total body (age 15–30), and total body (age 0–15)), fractures (in arm, spine, leg, heel, and osteoporotic fractures), and OP. Inverse variance weighted or Wald ratio was chosen as the main method for MR analysis based on the number of single nucleotide polymorphisms (SNPs). Furthermore, we performed sensitivity analyses to confirm the reliability of the findings.ResultsWe found a causal relationship between absolute retinol levels and heel BMD (p = 7.6E-05). The results of fixed effects IVW showed a protective effect of absolute retinol levels against heel BMD, with per 0.1 ln-transformed retinol being associated with a 28% increase in heel BMD (OR: 1.28, 95% CI: 1.13–1.44). In addition, a sex-specific effect of the absolute circulating retinol levels on the heel BMD has been observed in men. No other significant causal relationship was found.ConclusionThere is a positive causal relationship between absolute retinol levels and heel BMD. The implications of our results should be taken into account in future studies and in the creation of public health policies and OP prevention tactics.