Relationship between Serum Nutritional Factors and Bone Mineral Density: A Mendelian Randomization Study

Abstract

Purpose: Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD). Methods: Six nutritional factors were selected as exposures. Outcomes included total body BMD (n=66 945); BMD at the forearm (FA), femoral neck (FN) and lumbar spine (LS) (n=8143, n=32 735, and n = 28 498, respectively); estimated heel BMD (HL eBMD) (n=394 929); and HL eBMD stratified by sex (n=206 496). A 2-sample Mendelian randomization approach was adopted to estimate the association between serum nutritional factors and BMD. The threshold for adjusted P value was 1.39×10-3. Results: Serum calcium levels were inversely associated with LS BMD (effect=-0.55; 95% CI,-0.86 to-0.24; P=0.001), whereas serum selenium levels were positively correlated with HL eBMD (effect=0.22; 95% CI, 0.10 to 0.33; P=1.70×10-4). Regarding nominal significance, there was a positive association between serum selenium levels and FA BMD. Nominally significant results were also obtained for serum retinol as well as vitamin E levels and HL eBMD. Moreover, sex-specific effects of serum retinol and vitamin E levels on BMD were observed in men. Conclusion: Serum calcium and selenium levels influence BMD at specific skeletal sites. This implies that these nutritional factors play crucial roles in bone metabolism.