AACE: Early Treatment of Mild Paget's Yields Lengthy Remissions

SEATTLE, April 13 -- Early treatment of mild Paget's disease with pamidronate (Aredia) may promote longer remissions without additional bisphosphonate treatment, investigators suggested here.

Pamidronate infusions in divided doses over three weeks resulted in lengthy remissions that, in one case, lasted as long as 13 years, reported Brian C. Jameson, D.O., and Arnold N. Moses, M.D., of the State University of New York Upstate Medical Center in Syracuse.

Serum alkaline phosphatase levels less than two times the upper limit of normal at the time of diagnosis predicted a likelihood of longer remissions, the investigators noted in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists here.

"We suggest that patients with evidence of active Paget's disease by clinical, radiographic, or bone turnover criteria may benefit from early antiresorptive therapy," they wrote.

They conducted a retrospective chart review of 17 patients who were treated from 1994 to 1996 who had normalized serum alkaline phosphatase levels after treatment with intravenous pamidronate. The goal of the study was to determine factors predictive of long-term remission.

It was prompted by the success of an index case, that of a 74-year-old man who had been diagnosed with Paget's of the left hip after complaining of severe hip and left leg pain when he was both active and at rest.

Clinical studies showed that the patient had an elevated urinary deoxypyridinoline level of 15.3 nmol/mmol Cr, above the upper limit of normal (10.7). Yet his serum alkaline phosphatase level was within the normal range, 88 IU/L (normal range 21-126 IU/L). A technetium bone scan showed that he had increased uptake in the left pelvis.

He was infused with 180 mg of pamidronate in divided doses over three weeks, and soon after he had resolution of pain, normalization of both deoxpyridinoline levels and technetium scan, and his serum alkaline phosphatase bottomed out at 53 IU/L.

The patient has remained asymptomatic with normal bone-turnover markers and bone scans for more than 13 years.

On the basis of the success of this case, the authors looked at data on 17 additional patients who were treated for early Paget's disease with pamidronate from 1994 to 1996, when the bisphosphonate was still new to the U.S. market.

They found that patients with mild Paget's at the time of diagnosis, defined as a pretreatment serum alklaline phosphatase less than two times the upper limit of normal, had two-fold longer remissions (measured as duration of normal serum alkaline phosphatase levels) than those with moderate disease at diagnosis (serum alkaline phosphatase two to five times the upper limit of normal).

Of eight patients with serum alkaline phosphatase that was less than 200 IU/L before treatment, seven had remissions lasting at least 48 months. One woman with mild Paget's had a remission that had lasted 12 years at most recent follow-up, and a second woman had been in remission for eight years.

In contrast, of the six patients who had pre-treatment serum alkaline phosphatase levels that was more than 300 IU/L, five had remission lasting less than 40 months.

Of four patients with remissions lasting less than 30 months, three had received only 90 mg of pamidronate, rather than the 180 mg delivered to the other patients. The fourth patient was lost to follow-up.

The six patients with moderate disease pre-treatment had a median initial serum alkaline phosphatase of 369 IU/L and a median duration of remission of 19.5 months.

Although some investigators have recommended delaying treatment for Paget's unless the area of disease activity is in a weight-bearing bone, these data and that of other investigators suggests that patients with serum alkaline phosphatase levels less than twice the upper limit of normal will benefit from early treatment by having sustained remissions.

"As recent data suggests a total dose and time-dependent relationship between bisphosphonate therapy and the development of osteonecrosis of the jaw, early treatment may lessen total exposure to these compounds," they wrote.

The authors acknowledged that their study was limited by the retrospective chart review design, a lack of standardization or randomization of the therapeutic regimen, and the lack of a control population.