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Monthly Bisphosphonate as Effective as Daily


 

SEATTLE — Monthly dosing of the bisphosphonate ibandronate appears to be just as effective as daily dosing, according to the findings of a controlled study presented at the annual meeting of the American Society for Bone and Mineral Research.

Such findings are welcome, given that compliance with bisphosphonate regimens tends to be challenging. In addition to causing esophagitis, the drugs require long fasts before and after they are taken. Prescribing a bisphosphonate that requires monthly, rather than daily, dosing could potentially greatly improve compliance, noted Paul D. Miller, M.D., director of the Colorado Center for Bone Research in Lakewood, Colo.

Dr. Miller presented a randomized, blinded study comparing three different doses of oral ibandronate given monthly with the standard dose given daily. The monthly regimens consisted of two 50-mg doses (328 patients), a single 100-mg dose (311 patients), or a single 150-mg dose (320 patients).

All three of the monthly regimens were at least equivalent to the standard 2·5-mg daily dose regimen at improving bone mineral density over 1 year of treatment, he said in a poster presentation.

In the 318 osteoporotic women treated with daily ibandronate, lumbar spine density increased by a mean of 4%. All three of the monthly regimens produced similar increases, with the 150-mg dose increasing lumbar spine density by a mean of 4·5%.

Density measurements at the total hip and hip trochanter showed greater mean increases with the monthly dosing compared with daily dosing. Total hip density increased by a mean of 2% in the daily group, compared with 3% in the group taking 150 mg/month.

The overall rate of adverse events was similar in all the groups. Upper gastrointestinal adverse events were slightly higher with 150 mg/month than with the other regimens (20% vs. 18%), but the only patients who withdrew from the trial because of adverse events were in the daily and 100-mg divided-dose groups.

Moreover, the first-phase reactions that some patients have when they initially use a bisphosphonate—fever, arthralgia, and nausea—were no more common with the monthly regimen (10%-15%) than the daily regimen and no more severe, Dr. Miller said in an interview.

Standard-dose ibandronate (Boniva) was approved in May 2003. If the monthly formulation is approved it may help improve compliance, but there are no guarantees.

In a study tracking the compliance of 2,741 postmenopausal women receiving their first prescription of alendronate or risedronate, Joyce A. Cramer, of Yale University, New Haven, found that weekly dosing improved compliance over daily dosing, but that even with weekly dosing compliance is not very good.

Ms. Cramer analyzed prescription-fill rates and found that 44% of women prescribed weekly therapy and 31% of those taking it daily were still on medication after a year, according to her poster presentation.

Moreover, 31% of the women who had received a prescription for weekly medication filled them no more than twice compared with 21% of those on daily medication.

A trial looking at a large number of patients representative of those being treated in private practice showed that 45% of patients prescribed a weekly regimen were compliant at least 80% of the time.

Similarly, 33% of those prescribed a daily bisphosphonate were compliant at least 80% of the time, Robert R. Recker, M.D., said in a poster presentation.

Records from 211,319 patients who were followed for 1 year suggest that even with a once-weekly regimen, too few patients are compliant enough to be getting proper benefit from their treatment, said Dr. Recker, director of the Osteoporosis Research Center at Creighton University, Omaha, Neb.

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