Metabolic consequences of bone turnover in Paget's disease of bone.

High rates of bone resorption, bone formation, and marrow fibrosis are characteristic of Paget's disease of bone. This excessive bone turnover is reflected by increased fluxes of calcium ions out of and into the skeleton. The rates of these fluxes are highly geared to each other such that calcium balances are close to zero in the absence of fracture or significant immobilization. An increased turnover of bone matrix is also evident by increased urinary excretion of collagen breakdown products (oligopeptides of hydroxyproline, hydroxylysine, and hydroxylysine glycosides) as well as products (peptides of higher molecular weight) related to collagen synthesis. Increased circulatory levels of procollagen extension fragments reflect increased synthesis of Type I collagen (bone matrix) and Type III collagen (marrow fibrosis). Increased levels of bone gamma-carboxyglutamic acid-protein presumably reflect primarily bone matrix synthesis but bone resorption as well. When bone resorption is suppressed pharmacologically, the abnormal levels of these markers of matrix turnover and osteoblastic activity (alkaline phosphatase) also decrease, presumably as a result of coupling of resorption and formation.