Nanoengineered Bezafibrate-Loaded Calcium Nanoparticles for Osteoporosis: A Repurposing Approach for Targeted Bone Therapy

Osteoporosis is a progressive skeletal disorder characterized by an imbalance between bone resorption and bone formation, leading to reduced bone mineral density and increased fracture risk. Bezafibrate (BZ), a lipid-lowering fibrate, has recently gained attention as a promising repurposed therapeutic agent for osteoporosis due to its potential bone-protective effects. This study aimed to develop and evaluate a novel bezafibrate-loaded calcium nanoparticle (BZ-CNP) system to enhance its therapeutic efficacy against osteoporosis and assess its in vivo performance in an osteoporotic animal model. Calcium nanoparticles (CNPs), known for their biocompatibility and inherent bone-targeting capabilities, were formulated using the chemical precipitation method for efficient drug delivery to bone tissue. BZ-CNPs were optimized using Box-Behnken Design (BBD), and their physicochemical properties were thoroughly characterized. The therapeutic potential of the optimized formulation was evaluated in a dexamethasone-induced osteoporotic rat model. The optimized BZ-CNPs exhibited a particle size of 242.1 nm, a polydispersity index (PDI) of 0.302, and a zeta potential of −32.7 mV, indicating stable nanoscale dispersion. The entrapment efficiency was 87.2%, demonstrating efficient drug loading. In vivo and biochemical parameters results revealed a significant improvement in bone turnover markers, confirming the formulation's efficacy in reversing osteoporosis-induced bone loss. The developed Bezafibrate-loaded calcium nanoparticles represent a promising nanocarrier system for targeted delivery, offering enhanced therapeutic outcomes in osteoporosis management.