Goals of treatment for Paget's disease of bone.

The goals of treatment of Paget's disease must be readdressed in the context of the availability of potent bisphosphonate compounds, including pamidronate and, more recently, alendronate and risedronate. These agents differ from the traditional mainstays of therapy, salmon calcitonin and etidronate, in several respects. First, they achieve a reduction in the elevated indices of pagetic bone turnover of about 80%, in contrast with the 50% reduction seen with the older agents. Second, a majority of patients (in the range of 50-75%, depending on the series) achieve biochemical remission, and the duration of remission may exceed 1 year or more after a single course of therapy. Third, with the newer bisphosphonates the quality of newly forming bone after successful treatment is lamellar in appearance (as was the case with etidronate) but there is no clinically significant mineralization abnormality associated with these more recent agents. With prior therapies, the primary goal of treatment was to relieve symptoms. In the absence of complete suppression of abnormal turnover, disease progression was not completely halted in many patients, increasing the risk of long-term complications. The characteristics of the newer agents, however, suggest that in those patients who achieve remission there is a possibility, albeit not yet proven, of arresting progression and reducing the risk of later complications. Many patients have no symptoms at presentation but have active disease at locations where progression could cause bone enlargement and deformity over time. These patients may be considered to be at increased risk of future complications if untreated. Thus, it is recommended that such individuals receive therapy with a potent bisphosphonate with the goal of attaining normal (or near normal) biochemical indices after initial treatment and/or retreatment. Patients should be followed with measurement of serum alkaline phosphatase every 4-6 months after a course of therapy, and retreatment is suggested when indices rise above the upper limit of normal or by 25% above the previous nadir. The uncommon possibility of secondary resistance to a given agent after more than one treatment course should be assessed in all patients.