Coupling, the mechanism that controls the sequence of events in bone remodeling, is a fundamental theory for understanding the way the skeleton changes throughout life. This review is an adapted version of the Louis V Avioli lecture, delivered at the Annual Scientific Meeting of the American Society of Bone and Mineral Research in 2023. It outlines the history of the coupling concept, details how coupling is thought to occur within trabecular and cortical bone, and describes its multiple contexts and the many mechanisms suggested to couple bone-forming osteoblasts to the prior action of osteoclasts on the same bone surface. These mechanisms include signals produced at each stage of the remodeling sequence (resorption, reversal, and formation), such as factors released by osteoclasts through their resorptive action and through protein synthesis, molecules deposited in the cement line during the reversal phase, and potential signals from osteocytes within the local bone environment. The review highlights two examples of coupling factors (Cardiotrophin 1 and EphrinB2:EphB4) to illustrate the limited data available, the need to integrate the many functions of these factors within the basic multicellular unit (BMU), and the multiple origins of these factors, including the other cell types present during the remodeling sequence (such as osteocytes, macrophages, endothelial cells, and T-cells).
Keywords: coupling; osteoblast; osteoclast; osteocyte; remodeling.
Coupling is a fundamental process by which bone-resorbing cells (osteoclasts) are followed by bone-forming cells (osteoblasts) on the same surface during the process of bone remodeling. This review outlines the history, basic concepts, and mechanisms proposed, and suggests directions for further research into the way this sequence of events is controlled in bone maintenance, development, and healing.
© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.