title: Prediction of the outcome of treatment of Paget's disease of bone with bisphosphonates from short-term changes in the rate of bone resorption.
abstract: In Paget's disease of bone, bisphosphonate therapy is usually given for 3-6 months, at which point the success of treatment is assessed by measuring serum alkaline phosphatase activity. The changes, however, in bone resorption and formation after bisphosphonate therapy are predictable, and their correct interpretation may allow a rational therapeutic approach applicable to the individual patient. We addressed this issue in 21 patients with active Paget's disease treated with 2 different nitrogen-containing bisphosphonates for 10 days. Urine samples were collected daily before and during treatment for the measurement of the following collagen degradation products, as indexes of bone resorption; cross-linked N-telopeptide of collagen type I (NTx), free deoxypyridinoline with 2 different assays, and hydroxyproline. Independently of the structure of the bisphosphonate used, the magnitude of decrease in urinary NTx with treatment was greater than that of both deoxypyridinoline assays and practically identical to the decrease in excess of urinary hydroxyproline. The degree of suppression of NTx on the 9th and 10th days of treatment correlated with the lowest serum alkaline phosphatase activity obtained during 1 yr of follow-up. All patients in whom serum alkaline phosphatase activity normalized during follow-up showed a suppression of NTx greater than 75% of the initial values after 10 days of treatment. We conclude that urinary NTx is a sensitive and specific index to follow the efficacy of bisphosphonate therapy in patients with Paget's disease and that measurements of its values before and after a short period of treatment can provide a simple and convenient way to predict the final therapeutic outcome and to avoid unnecessary continuation of treatment in many patients with Paget's disease of bone.
authors.affiliation: Department of Endocrinology, University Hospital Leiden, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: Papapoulos
authors.forename: M
authors.initials: M
authors.lastname: Frölich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000032:analysis / Q000652:urine; D001862:Bone Resorption / Q000188:drug therapy* / Q000503:physiopathology* / Q000652:urine; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000503:physiopathology* / Q000652:urine; D010455:Peptides / Q000652:urine; D011379:Prognosis; D013997:Time Factors
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C036020:deoxypyridinoline; D003094:Collagen; D006909:Hydroxyproline