The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis.

The approximate equality of whole-body rates of formation and resorption over a wide range, a phenomenon frequently but inaccurately referred to as coupling, depends on the prompt and approximately complete refilling of each new resorption cavity with new bone. This focal regulation of bone balance requires an adequate supply of new osteoblasts at the right place at the right time, a process which presumably depends both on the availability of precursor cells and on some form of coupling signal. It also requires that each new osteoblast is able to make a normal amount of bone matrix, a process which is probably unrelated to coupling. The defect in bone formation that occurs in normal aging (and is exaggerated in osteoporosis) is too small a total work output by each new team of osteoblasts, so that refilling of resorption cavities is incomplete. Whether too few osteoblasts are assembled, which could result from a defect in a coupling signal or from deficiency of osteoblast precursors, or whether each osteoblast makes a subnormal amount of bone is unknown. Defective coupling, in the sense of a delay in the focal onset of bone formation after completion of resorption does occur in many patients with osteoporosis but makes only a minor contribution to bone loss. Imbalance between whole-body rates of resorption and formation in the absence of a coupling defect can also result from exaggerated depth of resorption cavities leading to perforation of trabecular plates and removal of some of the surfaces on which new bone is formed. The possible role of defective coupling in the pathogenesis of osteoporosis is still to be established.