Work

Zinc antagonizes cadmium-induced osteoporosis in mice by inhibiting Cd2+ deposition, enhancing antioxidant capacity and correcting bone metabolic disorders

Year: 2026

Type: article

Abstract: Chronic cadmium (Cd) exposure is a recognized risk factor for osteoporosis. Zinc (Zn) plays crucial roles in bone metabolism, yet intervention roles of Zn 2+ against Cd-induced osteoporosis are incompletely understood. The aim of this study was to investigate the antagonistic effect of Zn 2+ on Cd-induced osteoporosis and expose the underlying mechanism. Osteoporosis in mice was induced by exposing to low (5 mg/L) or high (50 mg/L) concentrations of Cd 2+ for 12 months, and a Zn intervention model was established by adding 30 mg/L Zn 2+ to the Cd-exposed mice. Results showed that Zn 2+ addition effectively alleviated pathological damage, mineral loss and destruction of trabecular structure of bones in osteoporotic mice caused by Cd. Cd exposure resulted in dose-dependent increases in serum calcium ion(Ca 2+ ) and phosphorus ion (P 3+ ) levels, while Zn 2+ addition significantly counteracted against the Cd-induced calcium and phosphorus metabolic disorders in serum. Zn²⁺ addition exhibited significant antagonism against Cd-induced abnormal serum bone metabolism indicators by suppressing elevated bone resorption markers (TRACP-5b and BALP), and restoring osteogenic markers of BGP, ALP, RUNX2 and OPG expressions in osteoporotic mice caused by Cd. Zn²⁺ supplement rescued Cd-impaired osteogenic differentiation and mineralization. In addition, Zn²⁺ significantly reduced Cd²⁺ deposition in bone tissue, while elevating bone Zn²⁺ levels in Cd-exposed mice. Importantly, Zn²⁺ supplement significantly enhanced metallothionein (MT) and metal regulatory transcription factor-1 (MTF-1) expressions in bone of Cd-exposed mice. Furthermore, Zn²⁺ addition inhibited osteoclast hyperactivation by reducing the number of TRAP-positive cells and suppressing the expression of osteoclast-related genes (Cathepsin K, MMP-9, OSCAR, TRAP, and RANKL) in Cd-exposed mice. Collectively, Zn 2+ addition exhibited notable antagonistic effects against Cd-induced osteoporosis in mice, and the mechanism of action was partly achieved by inhibiting the deposition of Cd 2+ in bone tissue, enhancing antioxidant capacity in bone, and correcting bone metabolic imbalance caused by Cd. • Cadmium exposure caused trabecular bone structure damage, bone loss, inhibition of osteoblast differentiation and enhanced bone resorption function in mice. • Zinc counteracted cadmium-induced osteoporosis by reducing Cd²⁺ deposition in bone tissue, enhancing bone antioxidant capacity through upregulation of metallothionein and metal regulatory transcription factor 1 expression. • Zinc addition promoted the expression of bone formation-related genes while simultaneously suppressing the expression of osteoclast differentiation-related genes in osteoporotic mice caused by cadmium.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2026.119688

Authors: Yingze Qin, Lisha Fan, Yi Feng, Ding Zhang, Chuan Xiang

Institutions: Shanxi Medical University, Second Hospital of Shanxi Medical University, Shanxi Agricultural University

Language: English

Topic: Heavy Metal Exposure and Toxicity

Subfield: Health, Toxicology and Mutagenesis

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,650