Beyond Bisphosphonates: Estrogen And SERMS

Patient Expert

While bisphosphonates Fosamax, Boniva, Actonel, and Reclast are the most powerful drugs we have to combat osteoporosis, they come with a host of potential side effects. If you're unable to deal with those side effects; and/or if your osteoporosis is mild, you may want to consider two other types of osteoporosis treatment: estrogen, and SERMs (selective estrogen receptor modulators).

There are various forms of estrogen available on the market. The broader class of these drugs, known as hormone replacement therapy drugs (HRT), have been taken by millions of women to deal with the side effects of menopause, one of which is osteoporosis. The most common HRT drugs are Prempro and Premarin.

How does estrogen strengthen your bones? Basically, estrogen hinders osteoclasts, the cells that break bone down; and helps osteoblasts, the cells that build it back up. Estrogen slows the amount of bone osteoclasts can absorb; and it increases the amount of calcium osteoblasts (the "good guys") can absorb. So bone breakdown is slowed, and the pace of bone buildup is increased.

Sounds good, right? Well, yes and no. Estrogen definitely helps slow/reverse osteoporosis. It's also been identified as a significant breast cancer and uterine cancer risk factor. So the use of HRT for osteoporosis has declined.

Nevertheless, if you're at very high risk for osteoporosis, your doctor may determine that the benefits of taking HRT (estrogen) may just outweigh its risks for you.

Premarin (estrogen) and Prempro (estrogen and progestin)
Is it recommended for me?
These drugs are very effective at preventing and treating osteoporosis in postmenopausal women, particularly in the 5 to 10 years just after menopause. However, the FDA does not recommend estrogen for the prevention of osteoporosis in postmenopausal women, unless the woman is at significant risk, and can't take non-estrogen medications.

Doctors are currently recommending that women take HRT in the lowest possible dose, for the shortest possible amount of time, in order to minimize the risk of cancer. So it's a tough balancing act: for its full benefit against osteoporosis, HRT should be taken for up to 10 years post-menopause; but taking HRT for that long increases your risk for cancer. The complicated decision to take HRT is made on an individual basis by a woman and her doctor.

How will it help me?
Estrogen builds bones all over your body, by both slowing their breakdown, and speeding their buildup; it offers equally effective protection against hip, spine, wrist, and any other type of fracture. In fact, studies show that women who take estrogen or estrogen/progestin during the first 5 to 10 years after menopause may reduce their risk of hip fracture during that timeframe by up to 50%.

When and how would I take it?
Premarin and Prempro are taken daily, in pill form. There's no special protocol for taking them, although it's a helpful memory aide to take them along with your daily vitamins and supplements.

And what are the common side effects?
Common side effects of Premarin and Progestin in post-menopausal women include breast pain/enlargement; vaginitis due to yeast or other causes, and leg cramps. Less common side effects include breast and uterine cancer; and heart attack.

Aprela is a pipeline drug that appears to have all the benefits of Prempro and Premarin, but without increased risk of breast and uterine cancer, or heart attacks. It's completed phase III clinical trials, and manufacturer Wyeth expects to file an NDA (new drug application) for Aprela sometime after the first half of 2009.

Selective estrogen receptor modulators (SERMs)
This type of drug has a split personality: in some parts of the body it acts like estrogen, while in others, it doesn't. Evista (raloxifene) is the SERM most commonly prescribed for osteoporosis.

So what's with the seemingly opposite effect SERMS have in different parts of your body? Why is that important? As mentioned above, estrogen is great for building bones. Unfortunately, for women with breast cancer (or those at identified high risk of getting it), estrogen is a no-no; it encourages breast cancer growth. Evista acts like estrogen on the bones, yet at the same time isn't recognized as estrogen by breast tissue. Thus it helps bones, but doesn't encourage breast cancer; a win-win for women.

Is it recommended for me?
Evista is recommended for the prevention and treatment of osteoporosis in post-menopausal women. It's not recommended if you have or have had blood clots in the legs, lungs, or eyes. Also, if you've had a heart attack (or are at risk for one), Evista may increase your risk of dying from a stroke.

How will it help me?
Evista stops the thinning of bones; increases bone mineral density (BMD); and helps balance bone turnover rate (the rate at which your bones break down, and build up). It's recommended as protection against first spinal fractures; and for subsequent spinal fractures as well, although its effect isn't as great there. Evista hasn't been shown to be effective protection against hip, wrist, or other types of fractures.

When and how would I take it?
Evista is a 60mg pill. You can take it any time of the day, with or without food. Unlike a bisphosphonate, there's really no protocol involved in how you take Evista, other than to be sure you take it every day. Since you can take Evista with both calcium and vitamin D, without negative effect, it's easy to take it along with your daily vitamins and supplements.

And what are the common side effects?
The most common side effects of Evista are hot flashes, leg cramps, swelling, flu-like symptoms, joint pain, and sweating. Less common, though serious, side effects include blood clots, and dying from stroke. Obviously, you'd discuss the risk of these serious side effects with your doctor.

A couple of other SERMS are in the drug pipeline, currently wending their way towards FDA approval. Viviant, which works similarly to Evista, should be up for FDA review sometime in the second half of 2009. Fablyn received FDA advisory committee approval last September, and will be up for review in early 2009.