The Bisphosphonates - Protecting Your Bones: Osteoporosis

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The bisphosphonates

The bisphosphonates are a family of drugs used to prevent or treat osteoporosis in postmenopausal women. They are also used to treat men in certain cases. These medications are often the first choice of doctors and patients alike. This is because they reduce hip, wrist, and spinal fractures, and when they are taken properly they have few side effects. These attributes have made bisphosphonates an attractive alternative to hormone therapy, which was once widely used for stemming bone loss but has fallen out of favor (see "Hormone therapy"). The bisphosphonates typically prescribed for osteoporosis are alendronate (Fosamax) and risedronate (Actonel). The FDA has also approved a newer medication called ibandronate (Boniva) for use in treating osteoporosis, but this drug isn't yet available as of the printing of this publication (see "Ibandronate").

Like most of the medications approved for treating osteoporosis, bisphosphonates are antiresorptive, meaning that they reduce bone resorption or turnover. They slow bone loss and produce modest increases in bone density. Specifically, the bisphosphonates bind themselves to hydroxyapatite (the cement-like substance in bones) and interfere with bone-depleting osteoclasts, narrowing the gap between osteoclast activity and osteoblast activity. As a result, osteoblasts (which build bone) have an opportunity to fill in more of the tunnels left by osteoclasts.

The bisphosphonates don't seem to interact with other medications and are usually well tolerated. They can be hard to digest and may cause nausea, heartburn, or irritation of the stomach or esophagus, but these problems can be alleviated if the medications are taken properly (see "How to take alendronate and risedronate"). Another advantage to these medications is that they are available in weekly as well as daily dosages; taking weekly doses may further reduce side effects.

How to take alendronate and risedronate Since both alendronate and risedronate can be difficult to digest, people taking these medications must follow instructions carefully to avoid unpleasant side effects such as heartburn, nausea, or difficulty in swallowing. (Although ibandronate is currently not on the market, it too should be taken in a similar manner.) The first thing in the morning, take either medication on an empty stomach with a large glass of water and then remain upright for at least 30 minutes. During this time, avoid eating, drinking, or taking another medication. It's important to take the medication with water, rather than coffee or orange juice, both of which can interfere with your body's ability to absorb and use the drug. Most people tolerate these medications well, when they take the pills as instructed. In fact, side effects are uncommon among people taking alendronate and risedronate in clinical studies. Perhaps these study participants are more likely to take their medications exactly as directed. The consequences of not taking alendronate properly became evident a few months after it was on the market. In March 1996, the manufacturer, Merck Pharmaceutical Company, notified physicians that the incidence of esophagitis, ulcers, and other gastrointestinal side effects among women taking the drug was higher than it had been during clinical trials. The company attributed these side effects to patients failing to drink enough water with the pills or returning to bed after taking the medication. Alendronate and risedronate thus may not be the best choice for those who have difficulty swallowing, recurrent heartburn, acid reflux, esophagitis, or stomach ulcers. It's important to take bisphosphonates with a large glass of water.

Alendronate (Fosamax)

Alendronate is commonly used to prevent or treat osteoporosis in postmenopausal women. In September 2000, alendronate became the first medication approved for treating men with osteoporosis. It is also approved to treat glucocorticoid-induced osteoporosis in both men and women.

Since 1995, when alendronate received its initial FDA approval, studies have consistently shown that it can slow or even halt bone loss, increase bone density, and reduce the risk for spinal and hip fractures. In the Fracture Intervention Trial, 2,028 women ages 55–81 who already had osteoporosis were randomly assigned to take either alendronate or a placebo. Over the three-year period, women who were taking alendronate had 47% fewer vertebral fractures and 51% fewer hip fractures than did those in the placebo group. And a multicenter study of women with osteoporosis found that the women taking alendronate had higher bone mineral density — 8.8% higher in the spine, 5.9% higher in the thighbone, and 2.5% higher in the total body — than women who weren't taking any medication.

Alendronate is also effective as a preventive medication. The Early Postmenopausal Intervention Cohort study, involving 1,600 women ages 45–59, found that women taking alendronate increased their bone mass by 3.46% in the spine and 1.8% in the hip. These increases closely matched those of women on hormone therapy, whose bone mass increased 4% at the spine and 1.83% at the hip. But alendronate does not have hormone therapy's other effects — either good or bad. While it won't alleviate menopausal symptoms, it also doesn't affect the risk for heart disease or breast cancer. That's because it is a highly specific drug. It travels preferentially to spots where bone turnover is high, such as the hips and spine. There it halts osteoclasts (the cells that break down bone) in their tracks and stalls bone resorption.

According to the Surgeon General's report on bone loss, studies indicate that alendronate seems to be safe and effective for up to 10 years and that it yields results quickly. A follow-up of the Fracture Intervention Trial found that alendronate was able to reduce the risk for spinal fractures within a year, and evidence of a reduced risk for hip fractures was seen at 18 months. The same study found that the medication worked well for most of the women taking it: 95% of the postmenopausal women using this medication maintained or increased their bone mass. In addition, the benefits of this medication seem to linger even after people stop using it. A study published in the Journal of Clinical Endocrinology and Metabolism in 2000 found that the bone mineral density of women who had taken alendronate for several years was maintained for two years after they stopped taking the drug.

Risedronate (Actonel)

Risedronate, like its cousin alendronate, is used to prevent and treat osteoporosis in postmenopausal women, and it may be used to prevent or treat glucocorticoid-related osteoporosis in men and women.

Also like alendronate, risedronate has been shown to impede bone loss, increase bone mineral density, and reduce the risk for fractures. According to the Surgeon General's report on bone health, studies of postmenopausal women have found that risedronate can increase bone mineral density in the spine by 5% and in the hip by 2%–3% after three years of use. Studies have also found that risedronate can cut the risk for spine fractures by 41% and hip fractures by 30%.

Like alendronate, risedronate works relatively quickly. A study published in 1999 in the Journal of the American Medical Association found that the medication could lower the risk for spine fractures after one year. In addition, risedronate seems to have few side effects, particularly when it is taken properly (see "How to take alendronate and risedronate"). According to the Surgeon General's report on bone health, studies have examined the safety of risedronate for up to five years and have found it to be safe and effective.

Ibandronate (Boniva)

This bisphosphonate has received FDA approval for preventing and treating osteoporosis. While the makers of the drug received approval for a once-a-day tablet, they don't plan to sell that product to consumers. Instead, they are focusing their efforts on a once-a-month version of ibandronate (see "Is a once-a-month or once-a-year treatment on the way?"). The two drug companies collaborating on this project, Roche Pharmaceuticals and GlaxoSmithKline, have already developed a tablet that is taken just once a month. At the time this report went to press, the once-a-month pill was still being tested and had not received FDA approval yet.

Like the other bisphosphonates approved for treating osteoporosis, ibandronate increases bone mineral density and helps prevent fractures. A study published in the Journal of Bone Mineral Research in July 2004 found that the medication cut vertebral fractures by half. The study, which included more than 2,900 women ages 55–80, also found that the women who took ibandronate every day increased their bone mass by 6.5% in the spine and 3.4% in the hip.

The side effects of ibandronate are similar to those of alendronate and risedronate. It can cause heartburn, ulcers, irritation of the esophagus, and difficulty with swallowing.

Last updated:	January 23, 2007