Recently, Sarah came to my office reporting that her doctor wanted her to take the bone drug raloxifene (Evista™). She wanted to know if I thought this medication would benefit her, so I sat down to take a fresh look at the first and largest controlled study on this drug.
The short version of what I discovered: there is limited benefit and substantial risks with this bone drug. But to understand why, you need to know the long version: what this drug does, and what it doesn’t do.
What is raloxifene (Evista™)?
Raloxifene is a “selective estrogen receptor modulator (SERM),” which puts it in the same family as the breast cancer drug tamoxifen (it was studied for breast cancer, but proved less effective than tamoxifen). SERMs bind to estrogen receptors and mimic estrogen’s effects; the idea is that you can get estrogen’s beneficial impacts on bone, but without the negative estrogen effects of on the uterus endometrial and breast tissue.
What raloxifene’s fracture prevention trial reveals
Back in the late 1990s, researchers conducted the first (and largest) placebo-controlled fracture prevention trial to determine what raloxifene might offer for osteoporosis. This trial involved 6,828 postmenopausal women divided into two treatment groups: One that was given a placebo, and the other given raloxifene in either 60 or 120 mg daily doses.
All of the study subjects had osteoporosis as determined by bone density measurement (–2.5 T score), and some of the women had already experienced a spinal fracture. The study was three years in duration.
Fracture reduction at three years:
- Of the 6,828 women in the study, 503 (7.4%) experienced at least one new vertebral fracture during the study period.
- In the placebo group, 10.1% experienced a vertebral fracture visible on x-ray (not necessarily symptomatic) during on the 3-year study.
- In the treatment group using 60-mg doses of raloxifene, 6.6% experienced a new vertebral fracture. This represents an absolute risk reduction of 3.5% — that is, among those using raloxifene, 3.5 fewer vertebral fractures occurred per 100 women as compared to those not taking the drug.
- Importantly, there was no significant reduction in hip fracture or other non-vertebral fractures with the use of raloxifene. While spinal fractures are a key warning sign for osteoporosis, they don’t affect quality of life nearly as much as hip fractures do.
All in all, this very large study showed that this drug had a small effect on reducing vertebral fractures and no significant effect on reducing hip or other non-vertebral fractures.
The risks of raloxifine lead to FDA black box warning
Unfortunately, even this very first study on raloxifene reported serious adverse effects, most notably a three-fold increase in the risk of potentially life-threatening venous blood clots (thrombosis).
Ten years after the drug was approved, the FDA issued a black box warning about this side effect — which is the most serious notification of potentially life-threatening adverse effects the FDA can require, short of withdrawing the drug from the market. I’ve reproduced it here so you can see what it says.
Is there a better way?
After looking at this information and comparing the mild possible benefits to the significant potential harms, Sarah and I have to ask the question: Is there a better way?
Currently, there are number of bone drugs prescribed to intervene with the mechanisms of skeletal weakening, and many more are in the pipeline. Given that up to half of the women 50+ in this country will be told to take a bone drug at some point, it’s a great idea to take a look at what these drugs do, the degree to which they really prevent fracture, and their potential risks, and what other avenues might be available to you.
Then make up your own mind.
Cranney A, Adachi JD. Benefit-risk assessment of raloxifene in postmenopausal osteoporosis. Drug Saf. 2005;28(8):721-30.
Duvernoy CS1, Yeo AA, Wong M, Cox DA, Kim HM. Antiplatelet therapy use and the risk of venous thromboembolic events in the Raloxifene Use for the Heart (RUTH) trial. J Womens Health (Larchmt). 2010 Aug;19(8):1459-65. doi: 10.1089/jwh.2009.1687.
Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282(7):637-645.