Introduction:The metal-organic frameworks (MOF) have shown fascinating possibilities in biomedical applications, and designing a drug delivery system (DDS) based on the MOF is important. This work aimed at developing a suitable DDS based on Denosumab-loaded Metal Organic Framework/Magnesium (DSB@MOF (Mg)) for attenuating osteoarthritis.Materials and Methods:The MOF (Mg) (Mg3(BPT)2(H2O)4) was synthesized using a sonochemical protocol. The efficiency of MOF (Mg) as a DDS was evaluated by loading and releasing DSB as a drug. In addition, the performance of MOF (Mg) was evaluated by releasing Mg ions for bone formation. The MOF (Mg) and DSB@MOF (Mg) cytotoxicity towards the MG63 cells were explored by MTT assay.Results:MOF (Mg) characterized by using XRD, SEM, EDX, TGA, and BET. Drug loading, and releasing experiments proved that DSB was loaded on the MOF (Mg) and approximately 72% DSB was released from it after 8 h. The characterization techniques showed that MOF (Mg) was successfully synthesized with good crystal structure and thermal stability. The result of BET showed that MOF (Mg) had high surface areas and pore volume. This is the reason why its 25.73% DSB was loaded in the subsequent drug-loading experiment. Drug release and ion release experiments indicated DSB@MOF (Mg) had a good controlled release of DSB and Mg ions in solution. Cytotoxicity assay confirmed that the optimum dose of it had excellent biocompatibility and could stimulate the proliferation of MG63 cells as time went on.Conclusion:Due to the high loading amount of DSB and releasing time, DSB@MOF (Mg) can be promising as a suitable candidate for relieving bone pain caused by osteoporosis, with ossification-reinforcing functions.