Once-Weekly Alendronate Superior to Raloxifene for Spine and Hip BMD

Peggy Peck

April 29, 2003

April 29, 2003 (New Orleans) — In a head-to-head study, once-weekly alendronate (70 mg) demonstrated significantly greater increases in bone mineral density (BMD) of lumbar spine, total hip, and hip trochanter than daily raloxifene (60 mg). Moreover, these benefits were "apparent within the first six months of treatment," said Risa Kagan, MD, co-medical director of FORE-Foundation for Osteoporosis Research in Oakland, California.

Dr. Kagan was lead investigator for the Efficacy of Fosamax vs. Evista Comparison Trial (EFFECT), a multicenter study. She presented preliminary results from EFFECT at the 51st annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Kagan said there was a two-fold increase in BMD at lumbar spine (the primary endpoint of the study) in patients in the alendronate group compared with patients receiving raloxifene. Comparing the secondary endpoints of total hip BMD, after a year of treatment patients in the alendronate group demonstrated a 2% increase in BMD compared with a 1% increase in patients in the raloxifene group. In addition, "the BMD at the hip trochanter increased 3.2% in the alendronate arm and 1.8% in the raloxifene arm," she said.

The response rate — defined as the number of patients who maintained or increased BMD — was 94% in the alendronate arm and 75% in the raloxifene arm.

Although the study did not include fracture data, Dr. Kagan told Medscape that there were "no clinically apparent vertebral or hip fractures in either arm." She said that "there were a variety of other fractures, including wrist, shoulder, and toe fractures, and those data will be presented at another meeting later this year."

Lois E. Wehren, MD, from the Department of Epidemiology at the University of Maryland, told Medscape that it is not possible to collect relevant fracture data in a one-year trial. "But I can understand why they did a one-year study. They wanted to have some comparison data with raloxifene."

Dr. Wehren, who wasn't involved in the study, said the results "are about what I would expect with alendronate. I think, however, that follow-up data at two years may be more interesting because there are data to suggest that while both raloxifene and alendronate promote increased BMD, this effect plateaus at a year or two with raloxifene, but not with alendronate."

EFFECT enrolled 455 women at 52 centers in the U.S. Patients were randomized in a 1:1 fashion to alendronate 70 mg once a week and daily placebo or raloxifene 60 mg daily and once-a-week placebo. BMD was measured at baseline and again at six and 12 months.

Ninety-two percent of the women in the study were white, with a mean age of 64 years (range, 37-89 years). The mean age at menopause was 47 years. Women who had a history of breast or uterine cancer or who had a history of bisphosphonate, parathyroid hormone, estrogen, estrogen analogue, or selective estrogen receptor modulator were excluded from the study. In addition to alendronate or raloxifene, women were given 500 mg of calcium and 400 IU of vitamin D daily.

The mean baseline posteroanterior lumbar spine T score was -2.50 and the mean total hip score was -1.76. "Fifty-three percent of the patients reported a history of fracture, but this may be misleading because it comes from a self-report questionnaire that asked about any fracture, at any time in their lives," said Dr. Kagan.

Dr. Kagan said that 11.2% of the alendronate patients discontinued the drug, and 10.3% of women in the raloxifene arm discontinued the study drug.

The study was funded by Merck & Co., Inc.

ACOG 51st Annual Clinical Meeting: Papers in Current Clinical and Basis Investigation, Paper 4S. Presented April 28, 2003.

Reviewed by Gary D. Vogin, MD