The Biochemistry of Paget’s Disease

Abstract

The characteristic biological abnormalities of Paget’s disease reflect the disordered bone remodeling. It is likely that the initial event in this disease is a focal, intense resorption of existing bone associated with the presence of abnormal large osteoclasts. At the point where the lesions are usually recognized, increased production of woven and lamellar bone is evident, as well as replacement of normal fatty and hematopoietic marrow with a loose fibrous stroma. Coupling of bone formation with bone resorption is evidenced by quantitative histomorphometry and can be confirmed by parallel charges in serum alkaline phosphatase levels and urinary hydroxyproline excretion, as well as by radiocalcium kinetics and measurements of other indexes of matrix protein synthesis and degradation. Although it has been assumed that the formation of pagetic bone is a coupled response to increased resorption, it should be emphasized that all pagetic bone is abnormal. The osteoblastic rate is high, the osteoblastic surface is increased, and the osteoblasts themselves are also probably not normal. The increase in osteoblast function could somehow result from contact of cell membranes of osteoclasts and osteoblasts or stromal cells or through release of some product of osteoclasts. Many of the remodeling events in Paget’s disease have been interpreted as consistent with an increased “birth rate” of all of the bone cell populations.^1–6