Research progress on osteoclast regulation by biodegradable magnesium and its mechanism

Abstract Continuous advancements in medical technology and biomaterials have underscored the significant advantages of biodegradable implant materials for bone repair and remodelling over traditional inert metallic implants. Notably, biodegradable magnesium-based materials have gained much attention because of their optimal corrosion rates. Importantly, extensive clinical experience has resulted in the use of biodegradable magnesium-based orthopaedic implants. Both preclinical and clinical studies have consistently demonstrated that Mg has an excellent ability to promote bone tissue formation, a process that is closely associated with the release of Mg2+ and other degradation byproducts. Bone metabolism depends on a dynamic balance of bone formation and bone resorption. Mg2+ has been shown to increase osteoblast (OB) activity while suppressing osteoclast (OC) formation, thus playing a crucial role in bone remodelling and regeneration. In terms of osteolysis inhibition, Mg2+ plays a multifaceted role. First, Mg2+ inhibits OC formation by modulating the activity of mature OCs, their migratory behaviour and the activity of precursor cells. Second, Mg2+ influences OC production by regulating the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Additionally, Mg2+ impacts bone resorption by altering the immune microenvironment and the levels of hormones and peptides within the body. Furthermore, the alkaline environment generated around the biodegradable magnesium implant and its degradation products (e.g., H2) also significantly inhibit osteoclast formation. Recent research on magnesium-based implants has focused predominantly on their osteogenic properties, with few systematic reviews addressing the mechanisms through which biodegradable magnesium alloys suppress osteoclastic activity. This paper summarizes the latest clinical research progress concerning biodegradable magnesium implant materials and their significant regulatory effects and discusses recent advances in the understanding of the regulatory mechanisms of action Mg-based biomaterials on osteoclasts, with the aim of providing a more theoretical basis for the clinical application of biodegradable magnesium-based implants.