UPDATE: OSTEOPOROSIS
A roundup of medical and other interventions that make a difference (or don’t, in some cases)
IN THIS ARTICLE
The gynecologic effects of lasofoxifene (reported separately) did not include an increased risk of endometrial cancer or hyperplasia. Although the incidence of endometrial polyps did increase, the polyps were all inactive. Vaginal bleeding, secondary to atrophy, doubled in comparison with placebo.
All-cause mortality did not increase significantly among women taking a daily dosage of 0.5 mg of lasofoxifene, but it did among those taking a dosage of 0.25 mg (38%) (P =.05). And only with the 0.25-mg dosage was there a trend toward more overall deaths due to cancer (P =.06). A biologic reason for these differences in the rate of death is lacking, but the fact that there was no increased mortality at the higher dosage suggests that the difference might be due to chance.
Raloxifene is the only SERM approved for the treatment of osteoporosis and for reduction of the risk of invasive breast cancer. In clinical trials, the SERM arzoxifene proved to be more potent than raloxifene at decreasing bone resorption and improving bone mass in post-menopausal women. However, compared with placebo, it was associated with a 2.3-fold increase in the risk of venous thromboembolic events (95% confidence interval [CI], 1.5–3.7) and twice the rate of endometrial cancer.6 As a result, because the drug did not appear to offer any therapeutic advantages over raloxifene, the drug’s sponsor withdrew its new drug application with the FDA.
Details of the Generations Trial
Cummings and colleagues explored whether 20 mg of arzoxifene daily would safely reduce the risk of fracture and invasive breast cancer in postmenopausal women who had low bone mass or osteoporosis. The study involved 9,354 women from 232 sites and 23 countries. Approximately 50% of participants had osteoporosis; the other 50% had low bone mass. Participants were randomized to arzoxifene or placebo in a blinded, prospective fashion.6
After 3 years, the cumulative incidence of vertebral fracture in patients who had osteoporosis was 2.3% lower among women taking arzoxifene than it was among those taking placebo, a 41% relative risk reduction (95% CI, 0.45–0.77) (P < .001). In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (hazard ratio [HR], 0.44; 95% CI, 0.26–0.76; P < .001), but there was no significant decrease in the risk of nonvertebral fracture.
The absolute difference in the 4-year cumulative incidence of venous thromboembolic events was 0.7% over 4 years. Nine cases of endometrial cancer occurred among women taking arzoxifene, compared with 4 cases among women taking placebo (P =.16). Two of the endometrial cancers in the arzoxifene group were serous adenocarcinomas; all others were endometrioid carcinomas. More cases of uterine polyps occurred in the arzoxifene group than among women taking placebo (66 [1.39%] versus 34 [0.73%]) (P =.002). The cumulative incidence of reports of vaginal bleeding was similar for placebo (2.8%) and arzoxifene (3.2%) (P =.25).
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