Bone Homeostasis and Repair: Forced Into Shape.

Mechanical loading is a potent anabolic regulator of bone mass, and the first line of defense for bone loss is weight-bearing exercise. Likewise, protected weight bearing is the first prescribed physical therapy following orthopedic reconstructive surgery. In both cases, enhancement of new bone formation is the goal. Our understanding of the physical cues, mechanisms of force sensation, and the subsequent cellular response will help identify novel physical and therapeutic treatments for age- and disuse-related bone loss, delayed- and nonunion fractures, and significant bony defects. This review highlights important new insights into the principles and mechanisms governing mechanical adaptation of the skeleton during homeostasis and repair and ends with a summary of clinical implications stemming from our current understanding of how bone adapts to biophysical force.