Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.