Biochemical markers of bone turnover in Paget's disease of bone

Although the measurement of total alkaline phosphatase activity in serum is a valid index to assess the activity of Paget's disease of bone and to monitor treatment efficacy, this marker may lack sensitivity in some cases. Among the various markers of bone formation and resorption that have been developed, serum bone specific alkaline phosphatase and procollagen I N-terminal peptide (PINP) for formation, urinary N-telopeptide (NTX) and alpha-C-telopeptide (CTX) for bone resorption have emerged as the most sensitive ones, and may be useful in the management of pagetic patients. We have recently shown that the beta-isomerization of type I collagen CTX is impaired in pagetic bone matrix characterized by the existence of woven bone, as compared to normal lamellar bone matrix. This abnormality results in a preferential urinary excretion of nonisomerized (alpha-CTX) over beta-isomerized (beta-CTX) that can be measured with specific immunoassays. Patients with active Paget's disease of bone are characterized by an abnormally high alpha/beta-CTX ratio which goes down to the normal range after bisphosphonate therapy, probably reflecting the lamellar structure of newly formed bone matrix in pagetic skeletal sites after treatment.