Pathophysiology of Osteoporosis

Abstract

The bone is a dynamic tissue that is continuously removed and replaced (i.e., remodeled) in order to (1) ensure adaptation of the skeleton to weight-bearing (shape is function), (2) repair microdamages (cracks) that result from mechanical stresses, and (3) allow for mobilization of calcium from the skeleton in order to maintain serum calcium homeostasis. Bone remodeling is initiated by the development and activation of osteoclasts, the bone-resorbing cell, which then release growth factors capable to activate osteoblasts, the bone-forming cell. The activities of bone removal and deposition are therefore coupled within each “bone multicellular unit” or BMU. After the completion of growth, the bone size and mineral content have reached its peak and will be maintained more or less unchanged during the adult life in absence of pathophysiological conditions thanks to moderate levels of bone remodeling that are perfectly balanced between resorption and formation within each BMU. In addition, the skeleton continuously responds to mechanical stimuli resulting from both muscle contraction and weight-bearing, by directly stimulating bone formation (i.e., without prior resorption), a process known as bone modeling. This process in particular is responsible for the increased bone diameter and bone mass observed in physically active individuals, furthermore in athletes. It is controlled by osteocytes, which are terminally differentiated osteoblasts that have lost their capacity to form new bone but are entrenched in the bone and form a dense network of “sensing” cells capable to respond to mechanical stimuli, as well as to microdamages, and control both modeling and local remodeling processes.