Novel Therapy Significantly Reduces Spinal Fractures In Postmenopausal Women With Two Years Of Therapy

Ettinger will present his interim data today (September 14) at the European Congress of Osteoporosis.

The MORE trial is a multicenter, Eli Lilly and Co. sponsored research study, which UCSF played a pivotal role in coordinating. It was designed primarily to evaluate the effect of raloxifene on bone mineral density (BMD) and spinal fractures in women with osteoporosis.

MORE investigators found that the osteoporosis prevention drug, raloxifene, significantly reduced the risk of spinal fractures in osteoporatic postmenopausal women who took the drug for two years without increasing their risk of uterine and breast cancer.

In addition, the drug was well tolerated and women who received raloxifene had no higher incidence of uterine bleeding and breast tenderness than those who took a placebo.

The two-year analysis demonstrated that women who had no spinal fractures upon entry of the trial and received raloxifene were 52 percent less likely to have a first spinal fracture and women with a previous spinal fracture were 38 percent less likely to experience a new spinal fracture than those women who received placebo.

The drug did not reduce the risk of other types of fractures, such as fractures of the hip, Ettinger said. He added that this is not unexpected because fractures other than those of the spine are much less frequent and the spine responds much faster to treatment compared to other bones.

To complement the fracture data, those taking raloxifene were also shown to have a 2 to 3 percent increase in bone density at the hip and spine after 24 months. During the MORE trial, 7705 osteoporatic postmenopausal women (average age 66.5 years old) were randomized to receive either 60 or 120 milligrams per day of raloxifene or a matching dose of placebo. One-third of the women had one or more spinal fractures at baseline; and two-thirds had a low bone mineral density without a spine fracture. The women were recruited from 180 sites in 25 countries.

"These are two-year interim results of the trial and this study will continue for five years to determine the long term effects of raloxifene on women," said Steven Cummings, MD, UCSF professor of medicine and epidemiology and an author of the study. "Raloxifene is a promising drug because previous data presented at the American Society of Clinical Oncology (ASCO) has shown that it reduced the risk of breast cancer by 70 percent in the same group of women."

Raloxifene belongs to a class of drugs called selective estrogen receptor modulators (SERMS), which block the actions of estrogen in some tissues, such as the breasts, and mimic estrogen in other tissues, such as the bones. Raloxifene is similar to other SERMS, such as tamoxifen, because it has a positive, estrogen-like effect on a woman's bones and cholesterol levels. However, raloxifene differs from tamoxifen and estrogen because it does not stimulate the lining of the uterus, Cummings said.

He added that compared to estrogen, raloxifene reduces the risk of breast cancer, and does not cause problems of uterine bleeding and breast tenderness, which may result in women not continuing therapy long term.

According to Cummings, raloxifene has been shown to cause hot flashes in 8 to 10 percent of the women who took the drug, leg cramps in 5 percent, and one out of 250 women per year experienced blood clots.

"Raloxifene and other SERMS are an exciting class of compounds but we need to learn a lot more about how they can best be used," said Dennis Black, MD, UCSF professor of medicine and epidemiology and one of the co-authors of the study. "This study adds an important piece of the puzzle."

Raloxifene was approved for the prevention of osteoporosis in the US by the Food and Drug Administration in December 1997. In Europe, the drug was recently approved for both the treatment and prevention of osteoporosis. It is marketed as Evista by Eli Lilly and Co., the sponsors of the clinical trials of the treatment.

Other researchers on the study are L.V. Avioli, C. Christiansen, F.J. Cohen, P.D. Delmas, S. Eckert, H.K. Genant, C.C. Gluer, R.K. Knickerbocker, K. Krueger, P. Lips, B.H. Mitlak, T. Nickelsen, J. Stakkestad, and J.R. Zanchetta.