Once-Monthly Risedronate Effective Against Osteoporosis

November 13, 2007 (Boston) — Once-monthly dosing of risedronate is as effective as once-daily dosing of the drug, findings from a new trial reveal. Pierre Delmas, MD, PhD, professor of medicine at the University of Lyon in France, presented results of the study here at the American College of Rheumatology 71st Annual Scientific Meeting.
The Monthly Evaluation of Risedronate Trial in Osteoporosis (MERIT-OP) was a 2-year, phase 3, randomized, double-blind, parallel-group study that compared the efficacy and safety of risedronate 150 mg once a month to risedronate 5 mg daily. Researchers recruited 1292 women who were at least 50 years of age (approximate average age, 64 - 65 years) and who had been postmenopausal for at least 5 years. To be admitted to the study, patients also had to have a bone mineral density (BMD) t-score of −2.5 or a score less than 2.0 and at least 1 prevalent vertebral fracture. The women were randomly assigned to receive risedronate 150 mg once a month (n = 650) or risedronate 5 mg daily (n = 642). All participants also received supplementary calcium (1000 mg/day) and vitamin D (400 - 1000 U). Baseline demographics, including incidence of prevalent vertebral fracture (32%) and lumbar spine BMD (mean t-score, −3.2), were similar between the 2 groups.
The primary endpoint for the study was noninferiority of risedronate 150 mg once a month compared with a 5-mg daily dose. This endpoint was assessed by percentage change from lumbosacral BMD measured at baseline to BMD measured at 12 months, using the last observation carried forward. "This means that if a patient discontinued the study at 6 months, then that data was considered as the endpoint, so it is a very conservative assessment," Dr. Delmas explained to attendees.
Secondary endpoints included lumbar spine BMD and BMD at other sites measured at 6, 12, and 24 months. In addition, investigators evaluated the bone remodeling biomarkers urinary N-telopeptide cross-links (NTX), serum C-terminal telopeptide (CTX), and bone alkaline phosphatase (BAP) at 3, 6, 12, and 24 months.
Investigators found no significant differences in BMD at any site between the 2 groups at 12 months and the endpoint. Lumbar spine BMD measurements increased about 4% in both groups. Total hip BMD increased approximately 2%, whereas trochanter BMD increased approximately 3.5% in both groups. In addition, mean percentage decreases in the biomarkers BAP (30%) and urinary NTX (50%) showed no significant differences between the once-monthly and daily regimens. Patients receiving 5 mg daily did show a significantly greater decrease in serum CTX compared with the patients receiving a once-monthly dose. Dr. Delmas explained that this difference may be because the patients receiving a once-monthly dose had serum CTX measured right before taking the monthly dose.
"Serum CTX is probably the most sensitive marker of bone resorption," Dr. Delmas told attendees. "There are data that show if these measurements are taken 5 to 7 days after the patient takes the monthly pill, you can see that there is about a 30% drop [in serum CTX] than if the measurement is taken right before the monthly dose."
The 2 dosing regimens had similar safety profiles, Dr. Delmas said. Approximately 6.2% of patients receiving a once-monthly dose reported a serious adverse event vs 4.2% of the patients receiving 5 mg/day. About 20% of the patients receiving a dose once a month reported upper gastrointestinal tract symptoms compared with about 17% of the patients receiving 5 mg/day. The study was not sufficiently powered to examine fracture risk, Dr. Delmas noted. Fracture rates were similar and very low in both groups.
"This new monthly risedronate regimen may provide another choice for patients who desire a less frequent dosing option," Dr. Delmas concluded.
Anthony Sebba, MD, FACR, who moderated the session, commented to Medscape Rheumatology on the study: "It suggests, based on the best available surrogates that we have, that there is equivalency and effect between once daily and once monthly. The hypothesis is that by taking this once monthly, adherence is encouraged and compliance is presumably better than it would be than on a daily dosing interval. Evidence is still coming in [on] whether this hypothesis is correct."
He added, "At a minimum, a once-a-month regimen is more convenient for patients, but patients will decide which they will prefer." Dr. Sebba is a rheumatologist in clinical practice and an assistant clinical professor at the University of South Florida in Tampa. He was not associated with the study.
The study was funded by Proctor & Gamble, Inc. Dr. Delmas is a consultant to Proctor & Gamble.
American College of Rheumatology 71st Annual Scientific Meeting: Abstract 2140. Presented November 10, 2007.