Lasofoxifene is a part of a class of drugs known as nonsteroidal selective estrogen-receptor modulators (SERMs). It has already been shown to decrease the bone loss and weakening associated with osteoporosis, like other SERMs, including tamoxifen and raloxifene. But until now its effect on other health conditions commonly experienced by postmenopausal women was unknown.
A new study shows that postmenopausal women with osteoporosis who took a 0.5-milligram daily dose of lasofoxifene had a 42% lower risk of vertebral (spinal) fractures and a 24% lower risk of non-vertebral fractures than those who took a placebo treatment.
The women who took lasofoxifene also had an 81% lower risk of estrogen-receptor (ER) positive breast cancer, a 32% lower risk of heart-related events like heart attack, and a 36% lower risk of stroke.
"This is the first SERM that reduces the risk of all of these conditions at once," researcher Steven Cummings, MD, of the San Francisco Coordinating Center at the California Pacific Medical Center Research Institute, says in a news release. "Not only did it reduce vertebral fractures, which was not unexpected, it also reduced the risk of non-vertebral fractures -- injuries to the arms, legs, ribs, hips -- that are the most common injuries to people with osteoporosis and the main causes of disability."
Although lasofoxifene is available in Europe, the FDA recently rejected a request for approval in the U.S., and some experts question whether its benefits surpass those of other SERMs already on the market.
Drug Fights Fractures and More
The study, published in the New England Journal of Medicine, followed 8,556 postmenopausal women with osteoporosis who were randomly assigned to receive either a 0.25-milligram or 0.5-milligram dose of lasofoxifene or a placebo over five years.
The results showed the 0.5-milligram dose was much more effective at lowering the risk of fractures and boosting bone density compared to the placebo.
Researchers found those taking the higher dose had a 42% lower risk of vertebral fractures compared to the placebo group vs. 31% in the low-dose group. The higher dose showed a 24% lower risk of non-vertebral fractures, but the change in the low-dose group after five years of treatment was not statistically significant.
Women taking the higher dose of lasofoxifene also experienced an 81% reduction in their risk of ER positive breast cancer and a 16% reduction in LDL "bad" cholesterol. The risks for a heart event or stroke were 32% and 36% lower.
But researchers say not all the results were positive. As with other SERMs, women taking lasofoxifene had double to nearly three times the risk of experiencing a serious blot clot of the deep veins.
The study was partially funded by Pfizer, the manufacturer of lasofoxifene, but an independent scientific advisory committee oversaw the study design and analysis and approved it for publication.
Do We Need Another Osteoporosis Drug?
In an editorial that accompanies the study, Caroline Becker, MD, of Brigham and Women's Hospital in Boston, questions whether the benefits of lasofoxifene shown in this PEARL (Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene) study are enough to merit entering an already crowded field of osteoporosis drugs.
According to PEARL study information submitted to the FDA, Becker says, lasofoxifene did not reduce the risk of new, symptomatic vertebral fractures after three years of treatment. Instead it only reduced the risk of vertebral fractures as shown by radiological (X-ray) evidence at five years.
In contrast, another SERM, raloxifene (Evista), has been shown to significantly reduce both new symptomatic vertebral fractures as well as those shown by X-rays.
"On balance, lasofoxifene seems to offer little, if any, advantage over raloxifene as an agent against osteoporosis," Becker writes. "Although the cardiovascular benefits reported in the PEARL trial seem impressive, one would need to treat 492 patients for one year to prevent a single major coronary event."
Also, because lasofoxifene has not been tested in women at high risk for heart disease, its safety in this group is unknown, she says.
"Given the plethora of drugs currently available for osteoporosis, studies of new agents should show clear benefits over existing agents," Becker writes. "On the basis of this criterion, the results of the PEARL trial suggest that lasofoxifene offers no major clinically important benefits over raloxifene for the skeleton, breast, heart, or reproductive tract."