Impact of circulating zinc and other micronutrients on heel bone parameters: New evidence from Mendelian randomization analysis

Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mass and increased fracture risk. This study employed a 2-sample Mendelian randomization analysis to investigate the causal relationships between circulating micronutrient levels and bone health indicators, including heel broadband ultrasound attenuation, quantitative ultrasound index, bone mineral density, and osteoporosis risk. Genetic instruments were derived from large-scale genome-wide association studies. Among all tested micronutrients, zinc uniquely demonstrated causal associations with heel bone parameters. Specifically, genetically predicted higher zinc levels were negatively associated with heel broadband ultrasound attenuation (odds ratio [OR] = 0.972, P = .001), quantitative ultrasound index (OR = 0.981, P = .002), and bone mineral density (OR = 0.969, P < .001). However, no significant causal effect was observed on overall osteoporosis risk (OR = 0.999, P = .217). Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy. These results help clarify the complex relationship between zinc and bone quality and fill a critical knowledge gap by demonstrating that while zinc correlates with specific bone parameters, it may not directly reduce osteoporosis risk. Further randomized controlled trials are needed to validate these findings and explore their clinical implications.