Cadmium exposure and osteoporosis: epidemiological evidence and mechanisms

Cadmium (Cd) is a toxic heavy metal with a long biological half-life, exerting adverse effects on most tissues and organs in the human body. Inhalation, ingestion, and skin contact are the main ways of exposure to Cd. Bone is one of the target organs of Cd. The aging of the population has been considered as the reason for the high incidence rate of osteoporosis, but recent studies have emphasized that the risk of osteoporosis is related to Cd exposure. With the widespread use of Cd-containing materials in industrial and agricultural activities, the risk of Cd exposure is worrying. This review covers the epidemiological, in vivo, and in vitro studies on Cd exposure and osteoporosis. Epidemiological evidence has emphasized a positive association between Cd exposure and the occurrence rates of osteoporosis and fractures. Experimental studies have demonstrated that Cd induces osteoporosis through both direct and indirect pathways. The indirect pathway encompasses inducing renal dysfunction to impair calcium and phosphorus metabolism, whereas the direct pathway consists of directly influencing bone cells. This review aims to emphasize that Cd exposure may be an overlooked risk factor for osteoporosis and to elucidate the direct and indirect molecular mechanisms by which Cd induces osteoporosis. Understanding the pathogenesis of Cd-induced osteoporosis is crucial for the development of preventive and therapeutic strategies.