Renewing interest in the study of intermediate metabolism and cellular bioenergetics is brought on by the global increase in the prevalence of metabolic illnesses. Understanding of the mechanisms that integrate energy metabolism in the entire organism has significantly improved with the application of contemporary biochemical tools for quantifying the fuel substrate metabolism with cutting-edge mouse genetic procedures. Several unexpected findings in genetically altered mice have prompted research into the direction of intermediate metabolism of skeletal cells. These findings point to the possibility of novel endocrine connections through which bone cells can convey their energy status to other metabolic control centers. Understanding the expanded function of skeleton system has in turn inspired new lines of research aimed at characterizing the energy needs and bioenergetic characteristics of these bone cells. Bone-forming osteoblast and bone-resorbing osteoclast cells require a constant and large supply of energy substrates such as glucose, fatty acids, glutamine, etc., for their differentiation and functional activity. According to latest research, important developmental signaling pathways in bone cells are connected to bioenergetic programs, which may accommodate variations in energy requirements during their life cycle. The present review article provides a unique perspective of the past and present research in the metabolic characteristics of bone cells along with mechanisms governing energy substrate utilization and bioenergetics. In addition, we discussed the therapeutic inventions which are currently being utilized for the treatment and management of bone-related diseases such as osteoporosis, rheumatoid arthritis (RA), osteogenesis imperfecta (OIM), etc., by modulating the energetics of bone cells. We further emphasized on the role of GUT-associated metabolites (GAMs) such as short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), indole derivates, bile acids, etc., in regulating the energetics of bone cells and their plausible role in maintaining bone health. Emphasis is importantly placed on highlighting knowledge gaps in this novel field of skeletal biology, i.e., "Osteometabolism" (proposed by our group) that need to be further explored to characterize the physiological importance of skeletal cell bioenergetics in the context of human health and bone related metabolic diseases.
Keywords: Osteometabolism; bone cells; bone pathologies; gut-associated metabolites (GAMs); metabolism.