Novel Insights into Osteoclast Energy Metabolism

Osteoclasts are crucial for the dynamic remodeling of bone as they resorb old and damaged bone, making space for new bone. Metabolic reprogramming in these cells not only supports phenotypic changes, but also provides the necessary energy for their highly energy-consuming activity, bone resorption. In this review, we highlight recent developments in our understanding of the metabolic adaptations that influence osteoclast behavior and the overall remodeling of bone tissue.

Osteoclasts undergo metabolic reprogramming to meet the energy demands during their transition from precursor cells to fully mature bone-resorbing osteoclasts. Recent research has made considerable progress in pinpointing crucial metabolic adaptations and checkpoint proteins in this process. Notably, glucose metabolism, mitochondrial biogenesis, and oxidative respiration were identified as essential pathways involved in osteoclast differentiation, cytoskeletal organization, and resorptive activity. Furthermore, the interaction between these pathways and amino acid and lipid metabolism adds to the complexity of the process. These interconnected processes can function as diverse fuel sources or have independent regulatory effects, significantly influencing osteoclast function. Energy metabolism in osteoclasts involves various substrates and pathways to meet the energetic requirements of osteoclasts throughout their maturation stages. This understanding of osteoclast biology may provide valuable insights for modulating osteoclast activity during the pathogenesis of bone-related disorders and may pave the way for the development of innovative therapeutic strategies.