Fracture Risk Factors Not Predictive for Raloxifene


WASHINGTON — Risk factors for fracture in women with coronary heart disease or at increased risk for coronary heart disease do not predict the likelihood that treatment with raloxifene (Evista) will reduce the incidence of clinical vertebral or nonvertebral fractures.

The findings are derived from a secondary data analysis of women enrolled in the Raloxifene Use for the Heart (RUTH) study presented at an international symposium sponsored by the National Osteoporosis Foundation.

In the main study, 5,057 postmenopausal women treated with raloxifene (60 mg/day) had a reduced incidence of clinical vertebral fractures, compared with 5,044 women on placebo. The drug had no effect on overall incidence of nonvertebral fractures, said Dr. Jane A. Cauley, vice chair for research and professor of epidemiology at the University of Pittsburgh, who presented the findings on behalf of her colleague Dr. Kristine E. Ensrud of the University of Minnesota, Minneapolis.

The women were selected for the RUTH study because they had established coronary heart disease (CHD) or were at elevated risk for CHD, not because they were at risk for fracture. “We wanted to explore whether the effect of raloxifene in this population differed by risk factors for osteoporosis,” said Dr. Cauley, who disclosed that she has significant financial relationships with several pharmaceutical companies, including Eli Lilly & Co., which makes Evista and supported the study.

For the study, the women had to be at least 55 years old and postmenopausal for at least 1 year. The women had either an office visit or a telephone contact biannually. Fracture risk factors were assessed at baseline, but bone mineral density was not measured. Clinical vertebral and nonvertebral fractures were ascertained at each biannual visit or telephone contact and were confirmed by x-ray or medical records. The women were followed for an average of 5.6 years.

Risk factors for fracture included older age, smoking, lack of exercise, prior fractures since the age of 50, family history of hip fracture, diabetes, and certain medications (including hormones, thyroid hormone, and statins). Women were also assessed for body mass index (BMI) and were asked about weight loss in the previous year.

The average age for both the treatment group and the placebo group was 68 years, and women older than 70 years accounted for 39%. The women were predominantly white (84% in both groups). About 6% of women in each group had a history of a fracture, whereas almost 10% in each group had a family history of fracture. About 20% of women in both groups had a history of hormone therapy. Both groups had an average BMI of 29 kg/m2.

The final regression model for nonvertebral fractures included older age, prior fracture history, and family history of hip fracture. The final regression model for clinical vertebral fractures included age and prior use of hormone therapy.

“There was no difference in the effect of raloxifene on nonvertebral fractures for any of the [individual] risk factors that we examined,” Dr. Cauley said. Likewise, whereas there was an overall reduction in clinical vertebral fractures for women on raloxifene, the reduction in treated women was similar regardless of which risk factor was assessed.

In the original study, researchers found no significant difference between the two groups in the primary end point of incidence of death from coronary causes, nonfatal MI, or hospitalization for acute coronary syndrome.

Raloxifene did reduce the incidence of invasive breast cancer (hazard ratio 0.56), primarily because of a reduction in estrogen receptor-positive invasive breast cancer, another primary end point (N. Engl. J. Med. 2006;355:125–37).


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