This project belongs to applied basic research in the field of medicine and health. Bone is the main accumulation organ and/or target organ for heavy metals. However, the damage of heavy metals to bone has not attracted enough attention at home and abroad, and the characteristics of bone damage of heavy metals are still unclear. This project explored the manifestations and characteristics of the osteotoxic effects of heavy metals such as cadmium, lead, and depleted uranium based on population epidemiological surveys, combined with animal and cell experiments, and introduced benchmark doses to assess the risk of heavy metal bone damage. This study took the lead in systematically discussing the main manifestations and characteristics of the osteotoxic effects of metals such as cadmium and depleted uranium from the aspects of bone mass (bone density/bone mineral content), bone microstructure, bone biomechanics and bone metabolism markers, revealing that bone is a target organ for heavy metals and an important accumulation organ for heavy metals such as cadmium and depleted uranium. This study was the first to study the prognosis and influencing factors of cadmium bone damage. It was found that 10 years after the termination of cadmium exposure, the impact of cadmium on bones still exists, and the prognosis of cadmium-induced bone damage is related to exposure level, age and gender. Women are sensitive to bone damage caused by heavy metals such as cadmium, especially elderly women are the key targets for the prevention and treatment of environmental heavy metal bone damage. At the same time, this study took the lead in introducing the benchmark dose into the risk assessment of bone damage of heavy metals such as cadmium and lead, understanding and developing the dose-response relationship from a mathematical perspective, calculating the exposure limits for bone damage of heavy metals such as cadmium and lead, and finding that bone damage of heavy metals is related to renal damage. This study also found that heavy metals have direct osteotoxic effects, which are manifested in the dual effects of inhibiting osteoblast bone formation and stimulating osteoclast bone resorption. It is also proposed that osteoblast-osteoclast coupling (OPG/RANKL) may play an important role in heavy metal bone damage at environmental levels. This study is of great significance for revealing the characteristics and mechanisms of heavy metal bone damage, the prevention and control of heavy metal bone damage and the formulation of safe exposure limits, and has important reference value for the formulation of public health policies. Based on the characteristics of heavy metal accumulation and bone damage revealed in this study, the governments of the contaminated areas have taken effective measures (including expropriation of land, residents eating commercial grains, changing to drinking water, etc.). At present, the cadmium load in the residents in the area has decreased and the degree of bone damage has improved. The overall research has reached the international advanced level, and some research contents have reached the international leading level. This research summarized and published 27 papers, with a total of 107 citations (91 citations by him), including 17 SCI papers, with a total impact factor of 37.9, and a total of 81 citations (66 citations by him). Participated in many domestic and foreign academic conferences to exchange research results, and won many excellent paper awards and poster awards. It has trained 3 doctoral students and 3 master's students engaged in heavy metals and radiotoxicology research. At the same time, we also pay attention to the training of personnel from grassroots cooperative units, which has promoted the prevention and control of local heavy metal pollution such as cadmium and lead.