WASHINGTON — An investigational selective estrogen receptor modulator appears effective in increasing bone mineral density in postmenopausal women with normal or low bone mass.
The randomized, placebo-controlled phase III trial also concluded that the drug, arzoxifene, did not significantly increase endometrial thickness compared with placebo. However, a larger study is necessary to confirm uterine safety in women who were not prescreened for a normal uterus, Dr. Susan B. Broy said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.
Because selective estrogen receptor modulators (SERMs) have beneficial effects other than bone building, they may be an attractive alternative treatment for osteoporosis, Dr. Broy said in an interview. “The main advantage is that SERMs can prevent breast cancer. This is not yet proven for arzoxifene, since those trials are in progress, but it has been shown for other SERMS,” said Dr. Broy, a rheumatologist and professor of clinical medicine at the Chicago Medical School, North Chicago. “This makes SERMS attractive for the younger postmenopausal woman who could benefit from breast cancer prevention and osteoporosis prevention from one drug.”
SERMS have a shorter duration of action on bone than do bisphosphonates, and also cause fewer side effects, she added.
The 24-month study comprised 331 postmenopausal women whose bone mass was either normal or low (T-score 0 to −2.5). The subjects' mean age was 54 years. The cohort excluded women with vaginal bleeding, abnormal gynecologic findings, or an endometrial thickness of more than 5 mm.
Subjects were randomized to either 20 mg day arzoxifene or placebo. By 6 months, patients in the active group had gained a mean 1% in bone mineral density at the lumbar spine and in the total hip measurement, while there were no significant changes in BMD in placebo patients. By 12 months, active patients had gained a mean 2% at the lumbar spine and stayed steady at the total hip, while placebo patients had lost a mean of 0.5% at the lumbar spine and 0.25% at the total hip.
By 24 months, patients taking arzoxifene had maintained the mean 2% gain at the lumbar spine and the mean 1% gain at the total hip, while those taking placebo had lost a mean of 1.5% at both the lumbar spine and total hip.
Markers of bone turnover also improved significantly in the arzoxifene group compared with the placebo group at 24 months. The drug appeared to have no effect on endometrial hyperplasia or cancer. Endometrial thickness decreased by a mean of 0.191 mm in the placebo group and increased by a mean of 0.160 mm in the active group, not a significant difference.
Three percent of patients taking arzoxifene experienced a serious adverse event compared with 6% of those taking placebo. Hot flashes occurred in 12% of the active group and 11% of the placebo group. There were three cases of breast cancer in the placebo group and none in the active group.
Dr. Broy has been a speaker and consultant for Eli Lilly & Co., which conducted the trial.