FORT LAUDERDALE, FLA. — Reduced responsiveness to repeat bisphosphonate treatment in patients with Paget's disease of bone appears to be limited to pamidronate and may not be a problem with the newer, more potent agents, Dr. Socrates Papapoulos said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.
“The issue of bisphosphonate resistance does not appear to be of primary importance for our clinical practice, especially with the more potent agents now available,” said Dr. Papapoulos, professor of medicine and director of bone and mineral research at Leiden (the Netherlands) University Medical Center.
For most patients with Paget's disease of bone, short courses of bisphosphonate treatment typically result in remissions of 2 years or longer, and recurrences usually respond well to a new course of treatment. However, there have been reports of reduced responsiveness on repeat treatment. This so-called acquired resistance is characterized by a decrease in the magnitude of response, a need for higher doses to achieve the same response, and a shortening of the remission period compared with the initial treatment, he explained.
Previous literature on the subject has been confusing, particularly in the way responsiveness is measured. Some consider fractional decreases in serum alkaline phosphatase (AP) to be indicative of responsiveness, which is not valid because those values will almost always be lower on retreatment than at baseline, he said, adding that absolute serum AP values must be reported in order to assess the phenomenon of resistance.
To examine this issue, Dr. Papapoulos and his associates reviewed the records of 205 Paget's disease patients who had received two or more consecutive courses (up to nine courses) of either pamidronate or olpadronate. They received a total of 807 treatment courses with a mean follow-up per treatment of 29 months.
Overall, there was no difference in responsiveness—defined as a progressive increase in nadir serum AP—after initial versus subsequent treatment, nor was there a shorter period of remission following treatment. However, when the patients who had received only pamidronate were examined separately, there was a trend toward reduced responsiveness with pamidronate.
When the pamidronate patients were divided into those who had three or more affected bones versus those with two or fewer affected bones, the trend was seen only among those with more extensive disease. This finding is consistent with previous reports of acquired resistance to pamidronate in patients with extensive Paget's disease, Dr. Papapoulos noted.