Homeostatic control of bone structure: an application of feedback theory.

The regulation of bone mass and structure in the weight-bearing skeleton is governed to a great extent by the mechanical demands placed upon the bone tissue. The apparent biological goal is the maintenance of a minimum adequate structure, in which the margin of safety between normal mechanical demands and fracture is balanced by the cost of excessive bone mass on mobility. Frost has developed two powerful postulates concerning bone adaptation: (a) there exist threshold levels of mechanical strain, above or below which bone adaptation is turned on, and (b) the set point for normal bone structure can be modulated by hormones. A model was developed, using Frost's postulates and simple feedback theory, that describes the interaction between biochemical influences and mechanical influences on bone structure. The model predicts that biochemical agents that influence bone structure independently of the mechanical feedback system (e.g., calcitonin) are capable of only limited anabolic effects on bone mass because their influences conflict with mechanical influences. However, biochemical agents that influence bone structure by changing the set point of the mechanical feedback system (e.g., estrogen) will provide lasting changes in bone structure. Age-related changes occur within the effector and transduction components of the mechanical feedback system that tend to make it sluggish. These changes may lead to increased bone fragility because the system is no longer capable of maintaining adequate bone structure.