Metallic Contaminants and Osteoporosis: a Review of the Gut-Bone Axis.

Metal contaminants are frequently present in air, soil, drinking water, and food. Their adverse effects on the gut through intestinal exposure are multifaceted. These include dysbiosis of the intestinal flora, increased intestinal permeability, and inflammatory manifestations, and a decrease in short-chain fatty acids, indirectly aggravating bone damage. In addition, intestinal wall damage may further promote metal accumulation in the organs. Ultimately, exposure to metal contaminants disrupts the osteoclast-osteoblast balance through pathways such as NF-κB and RANKL/OPG. Although existing studies have examined the effects of individual metal contaminants on bone, gut, and microbiota, our understanding of the “gut-bone axis” mechanism—whether from single or mixed metal exposure—remains confined to individual organs. Furthermore, there is a lack of research on the causal mechanisms linking metal contaminants exposure in real-world environments and individual variations to their outcomes. Clarifying these causal mechanisms is essential to guide preventive strategies. Therefore, the purpose of this review is to examine the effects of exposure to common metal contaminants on intestinal and bone metabolism by categorising them into three groups: (1) heavy metals (cadmium, lead, mercury, arsenic, chromium); (2) trace elements (iron, copper, aluminium); and (3) mixed metal exposure. Finally, evidence from animal, human, and in vitro studies indicates that metal contaminants not only directly exacerbate osteoporosis but may also indirectly influence bone metabolism through the “gut-bone axis” pathway. Therefore, this review focuses on this field, aiming to elucidate the mechanisms by which environmental pollutants influence metabolism through the gut-bone axis, thereby providing critical theoretical foundations for the prevention and control of related health risks.