Raloxifene is a selective estrogen receptor modulator that inhibits bone resorption. Long-term estrogen therapy has been thought to reduce the incidence of fracture in this population, but studies thus far have not proved this conclusively. Ettinger and colleagues reviewed evidence from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial to assess the effect of raloxifene on fracture risk in postmenopausal women with osteoporosis.
The MORE trial consisted of post-menopausal women up to 80 years of age who had osteoporosis (bone density of at least 2.5 standard deviations below normal for young women) or at least one moderate (or two mild) vertebral compression fracture. Women with nonosteoporotic bone disease, breast cancer, endometrial cancer or a recent history of taking estrogens, androgens, bisphosphonates or calcitonin were excluded. Women who met the study criteria were randomized to receive placebo, 60 or 120 mg of raloxifene. All women received 500 mg of calcium and 400 to 600 IU of cholecalciferol daily. Vertebral radiographs were obtained at baseline, and again two and three years after baseline. Radiographs also were obtained at six-month intervals in women who had symptoms of a vertebral fracture.
Radiologists who interpreted the radiographs were blinded to the assigned group for each patient. Vertebral fractures were scored from zero (none) to 3 (severe fracture). A change of at least one point was defined as an incident fracture. Nonvertebral fractures were found by questioning patients at each six-month follow-up visit. Traumatic fractures, pathologic fractures and finger, toe and skull fractures were excluded from the analysis.
Bone mineral density of the spine and femoral neck was assessed with dual-energy x-ray absorptiometry (DEXA). Patients had to withdraw from the study if their bone mineral density decreased by at least 7 percent in the lumbar spine or 10 percent in the femoral neck, or if they had more than two incident vertebral fractures during the study period. All adverse effects were analyzed. The primary end point was the effect of raloxifene on the incidence of vertebral fractures and bone mineral density.
A total of 7,705 women were included in the MORE trial and of these, 6,828 had baseline imaging studies available for analysis. At the end of the study period, 7.4 percent of the women had at least one new vertebral fracture. Those taking 60 or 120 mg of raloxifene had fewer new fractures (6.6 and 5.4 percent, respectively) than those taking placebo (10.1 percent). The actual incidence of fracture did not differ significantly between treatment groups nor did the risk of fracture differ between treatment groups when analyzed by age, baseline bone mineral density, history of prior hysterectomy or history of hormone replacement therapy. Nonvertebral fractures also were more prevalent in the placebo group (9.3 percent) when compared with the pooled treatment groups (8.5 percent). These figures were not statistically significant, although the risk of ankle fracture was significantly reduced in the treatment groups.
Overall, bone mineral density increased at the femoral neck and spine in the treatment groups compared with the placebo group, with greater increases in the group taking 120 mg of raloxifene. Serious adverse effects occurred in about 24 percent of all women, regardless of the group. The only adverse effect associated with raloxifene use was thromboembolic events, with patients in the treatment groups at three times the risk of the placebo group. The risk of breast cancer was also diminished in the raloxifene groups (relative risk = 0.3).
The authors conclude that a 36-month course of raloxifene reduces the risk of vertebral fractures by 30 to 50 percent in post-menopausal women with osteoporosis, regardless of whether the patient had vertebral fractures at baseline. In contrast, some studies have shown that tamoxifen, another selective estrogen receptor modulator, decreases risk by only 19 percent.