TREATMENT OF PAGETS-DISEASE WITH OLPADRONATE - ASSESSMENT OF EFFICACYIN PARTIAL RESPONDERS TO PAMIDRONATE

Bisphosphonates are the treatment of choice in patients with Paget's d isease. However in patients with an extensive disease it has been diff icult to achieve complete biochemical remission. We studied the effica cy of the new bisphosphonate: Olpadronate (dimethyl APD) in 37 patient s (21 men and 16 women) with Pager's disease of (X +/- 1SD) 68 +/- 8 y ears of age: Group I: 12 patients without previous specific treatment. Group II: 25 patients who had been treated before (time free of treat ment before olpadronate: 11 +/- 8 months). (Table 1). Olpadronate was given orally in doses of 100 to 200 mg/day. Initial dose and/or increm ent of the dose during treatment were decided accordingly to the bioch emical response. The length of therapy was (X +/- 1SD) 3.5 +/- 2.4 mon ths (range 0.5 - 13 months) and was adjusted to the changes produced u pon the biochemical indexes of bone turnover. Olpadronate was well tol erated by all the patients except for one who discontinued the treatme nt due to gastrointestinal symptoms. Mean alkaline phosphatase (APh) d ecreased in both groups of patients as follows: Group I: basal: 36 +/- 20 KAU, final: 12 +/- 3 KAU (normal range: 5 to 15 KA units) and grou p II: basal 45 +/- 30 KAU final 14 +/- 10 KAU. (Table 2). Normalizatio n of APh was observed in all patients of group I and in 21/25 patients of group II. Three patients of group II had partial responses (60% of diminution of APh without reaching normal values) and treatment was n ot effective in 1 patient. The length of remission was 8.7 +/- 5.7 mon ths in group I and 10.4 +/- 8.1 months in group II. There was a signif icant inverse correlation between duration of remission and APh level post treatment. Fourteen patients of group II (7 women and 7 men) had previously received oral pamidronate (APD) in different cycles during a period of 6.6 +/- 4.2 years. After the first APD cycle, only 2 out o f 14 achieved normal APh values and none of the 14 achieved complete b iochemical remission after the last APD cycle. Olpadronate caused a si gnificant decrease of serum APh and THP compared to the lowest values observed during APD treatment. Normalization of APh was observed in 12 /14 of these partial responders to APD. (Table 3 and Figure 1). In con clusion, oral Olpadronate in a dose of 100 to 200 mg was well tolerate d and effective in the treatment of Paget's disease even in those prev ious partial responders to APD.