Bone cell precursors and the pathophysiology of bone loss

In health, changes in bone formation and degradation rates are coupled and adequate cellular resources are available in the bone so that a change in bone formation rate occurs with an opposing change in resorption. On the other hand, the regulation of bone volume, particularly in pathological conditions, is dependent not only on the pathways that mediate terminal pathways of bone cell differentiation, but also on the availability of stem cells for allowing the differentiation to occur. Regulation of cell numbers in stem cell compartments and release of stem cells for differentiation of osteoblast or osteoclast precursors are not well understood, although it is clear that changes in stem cell numbers underlie pathological changes in bone mass. This may include effects of aging, fracture, metastatic disease, and autoimmune diseases on the precursor cell pools available for bone formation and degradation. Increases in osteoclast precursors or decreases in osteoblast precursors are common features of bone-losing states; increases in precursors may conversely occur during growth or repair processes. Rational therapy based on modifying stem cell populations may, when the processes are better understood, help prevent chronic bone-losing states and may also be of use in preventing or treating aplastic anemia and related conditions.