Manganese Deficiency and Mn2O3 Nanoparticles Supplementation Disrupt Bone Remodeling and Mineral Matrix Maturation in Rats

This study aimed to investigate the effects of dietary manganese deficiency and compare the impact of manganese macroparticles (MnCO3) and nanoparticles (Mn2O3NPs) on bone remodeling and metabolism. Twenty-seven male Wistar rats were divided into three groups (n = 9): control (standard MnCO3, 65 mg Mn/kg), manganese-deficient, and Mn2O3NPs-supplemented (65 mg Mn/kg). After a 12-week feeding period, bone-related markers and gene expression were analyzed in the femur and blood. Mn-deficient rats showed reduced plasma levels of bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase 5b (TRAP5b), interferon-β (IFN-β), RANKL glycoprotein, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), vitamin K2, and collagen turnover markers (PINP, CTX-1, NTX). Femur levels of BALP, TRAP5b, interferon-γ (IFN-γ), osteonectin, calcitonin, PICP, PINP, and CTX-1 were also decreased. Replacing MnCO3 with Mn2O3NPs increased IFN-γ but lowered IFN-β and 1,25-(OH)2D3 levels in plasma. This treatment also decreased the femur level of BALP and calcitonin, and the RANKL:OPG ratio, while increasing the expression level of Sp7 and Ctsk genes. To conclude, our results suggest that manganese deficiency is associated with suppressed bone turnover and altered mineral metabolism. Furthermore, replacing MnCO3 with Mn2O3 nanoparticles did not yield the anticipated benefits for bone remodeling, as evidenced by the observed imbalances in osteogenic and resorptive markers, indicating a need for cautious evaluation of nanoparticle-based supplementation.