Skeletal metabolism in Paget's disease of bone

Paget's disease of bone is characterized by focal resorption of existing bone followed by the deposition of woven and lamellar bone in a characteristic pattern. Although bone turnover may be markedly increased, the coupling between formation and resorption is maintained. Metabolically there is increased efflux and influx of mineral ions in the involved areas. In addition, there is a parallel increase in resorption of matrix components, particularly collagen, with increased excretion of degradation products containing 4-hydroxyproline, hydroxylsine, and its glycosides. A portion of the urinary 4-hydroxyproline and hydroxylysine is in the form of peptides of approximately 5,000 daltons which appear to be related to collagen synthesis. Circulating levels of other organic matrix components are also increased such as procollagen fragments and the gamma-carboxyglutamic acid-bone protein. The increased levels of most of these metabolites return toward normal with specific therapy. The pattern of change suggests that bone resorption is decreased initially with therapy followed by a coupled decrease in formation.