PREDICTION OF THE OUTCOME OF TREATMENT OF PAGETS-DISEASE OF BONE WITHBISPHOSPHONATES FROM SHORT-TERM CHANGES IN THE RATE OF BONE-RESORPTION

In Paget's disease of bone, bisphosphonate therapy is usually given fo r 3-6 months, at which point the success of treatment is assessed by m easuring serum alkaline phosphatase activity. The changes, however, in bone resorption and formation after bisphosphonate therapy are predic table, and their correct interpretation may allow a rational therapeut ic approach applicable to the individual patient. We addressed this is sue in 21 patients with active Paget's disease treated with 2 differen t 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 resorptio n: cross-linked N-telopeptide of collagen type I (NTx), free deoxypyri dinoline with 2 different assays, and hydroxyproline. Independently of the structure of the bisphosphonate used, the magnitude of decrease i n urinary NTx with treatment was greater than that of both deoxypyridi noline assays and practically identical to the decrease in excess of u rinary hydroxyproline. The degree of suppression of NTx on the 9th and 10th days of treatment correlated with the lowest serum alkaline phos phatase activity obtained during 1 yr of follow-up. All patients in wh om serum alkaline phosphatase activity normalized during follow-up sho wed 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 pat ients with Paget's disease and that measurements of its values before and after a short period of treatment can provide a simple and conveni ent way to predict the final therapeutic outcome and to avoid unnecess ary continuation of treatment in many patients with Paget's disease of bone.