Amorphous calcium phosphate tagged benzimidazole derivative MR10 nanoconjugate mitigates corticosteroid induced secondary osteoporosis <i>in vivo</i>

Corticosteroid-induced osteoporosis leads to accelerated bone loss with associated oxidative stress, necessitating novel targeted therapeutic approaches. This work evaluates the protective efficacy of amorphous calcium phosphate-tagged benzimidazole derivative MR10 (ACP-MR10) nanoconjugate (NC) for its ability to counteract dexamethasone (DEX)-induced skeletal deterioration in zebrafish. ACP-MR10 NCs effectively mitigated ROS accumulation, restored antioxidant defences and preserved skeletal integrity and locomotor function, showing the strongest protective effect. ACP-MR10 significantly preserved DEX-induced mandibular bone deterioration. ACP-MR10's osteoprotective ability visualised through micro-CT also showed enhanced bone mineralisation, with improved trabecular architecture and vertebral alignment. ACP-MR10 treatment restored calcium and phosphorus levels, supporting robust skeletal regeneration. Molecular analysis showed suppressed <i>rankl</i> and <i>runx2b</i> expression while upregulating <i>opg</i> and <i>alp</i>, promoting balanced bone remodelling. Overall, these results point out ACP-MR10 as a credible candidate for its ability to provide a protective effect for bones capable of countering corticosteroid-induced osteoporosis by redox regulation, increased mineralisation, as well as structural retention of the skeleton.