Amorphous calcium phosphate tagged benzimidazole derivative MR10 nanoconjugate mitigates corticosteroid induced secondary osteoporosis in vivo.

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 rankl and runx2b expression while upregulating opg and alp, 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.