The "Mechanostat Theory" of Frost and the OPG/RANKL/RANK System

ABSTRACT Frost's great interest to elucidate the principles of action underlying skeletal deformities, during, and after growth, urged him to undertake an extensive study of the mammalian skeleton. He suggested that survival of the skeleton (but also of other tissues, such as fibrous tissue, hyaline cartilage, fibrocartilage, cementum, or dentin) requires the functional coordination of modeling and remodeling. Modeling adapts bone to overloads, by enhancing additions of new bone and by changing bone architecture, and remodeling adapts bone to underloads by removing bone next to marrow and conserving normally used bone. There exists a mechanism that monitors bone metabolism (longitudinal growth, bone modeling, and remodeling activities) in relation to mechanical usage, the “mechanostat.” Recent literature has presented new information regarding the physiological procedure of osteoclast and osteoblast activation. It has been understood that the OPG/RANKL/RANK proteinic system regulates bone metabolism by exerting biological effects on osteoblasts or osteoclasts. The same proteinic network, also regulates alveolar remodeling during tooth movement, as well as physiological root resorption and root resorption during orthodontic tooth movement. The aim of the present review is the presentation and evaluation of recent information in the field of osteoclast and osteoblast biology, as regards to the “mechanostat theory” of Frost. An attempt will be made to elucidate, whether recent data can support this remarkable theory and reveal the biological mechanisms behind it. J. Cell. Biochem. 116: 2724–2729, 2015. © 2015 Wiley Periodicals, Inc.