Thigh fractures linked to osteoporosis drugs; long-term use questioned

Since bisphosphonates such as alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), and zoledronic acid (Reclast) were first introduced in the mid-1990s, they’ve become a staple of osteoporosis treatment. Yet an FDA review recently published in The New England Journal of Medicine questions whether there’s any benefit to staying on these drugs long-term—especially considering their potential for side effects. A report released today in the Archives of Internal Medicine highlights one of those side effects, linking bisphosphonate use to a higher risk of unusual fractures in the femur (thighbone).

If you’ve been taking bisphosphonates long-term, you may be wondering, “What now?” “Although there isn’t any big change in recommendations, it reminds us that only individuals who really need these drugs should be taking them,” says Dr. Celeste Robb-Nicholson, editor in chief of Harvard Women’s Health Watch. If you’ve been taking bisphosphonates for less than five years you probably don’t need to change what you’re doing. But if you’ve been on these drugs for more than five years, talk to your doctor about whether it’s worth continuing.

Bisphosphonate benefits—and risks

Each year, doctors write millions of prescriptions for bisphosphonates. Studies have shown they help prevent spine and hip fractures, at least when they’re used over the short term (for three to four years). Yet even though many people stay on bisphosphonates indefinitely, there hasn’t been much research to support their use beyond five years.

Here’s how bisphosphonates work: Bones undergo a constant process of breakdown (called resorption) and rebuilding. When bones break down faster than they can rebuild, they become weak—the condition known as osteoporosis. Weakened bones make people more vulnerable to fractures if they fall. Bisphosphonates decrease bone resorption, which helps maintain bone density and keep the skeleton strong.

That’s all good. Yet bisphosphonates—like most drugs—can have side effects. As we wrote in the October 2010 Harvard Women’s Health Watch, one such side effect is atypical fractures of the thighbone. The study released today in the Archives of Internal Medicine adds further support to this connection. In this study of 477 people, 82% of those with atypical fractures were taking bisphosphonates. Only 6.4% of patients who had a classic femur fracture were on the drugs. Bisphosphonates have also been implicated in a rare, but very serious bone disease of the jaw (called osteonecrosis) in women who undergo dental procedures involving the jaw while taking these drugs.

What the FDA found

To determine whether bisphosphonates continue to deliver any benefits after five years, the FDA looked at three long-term bisphosphonate studies:

• Fosamax Fracture Intervention Trial Long-Term Extension (FLEX)
• Reclast Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) extension
• Actonel Vertebral Efficacy with Risedronate Therapy—Multinational Trial (VERT-MN) extension

Up to five years of treatment, bisphosphonates did help reduce fracture risk. Beyond that period, their benefits seemed to taper off. People in these studies who continued taking bisphosphonates for six years or more had fracture rates of 9.3% to 10.6%. By comparison, those who switched to an inactive placebo after five years had fracture rates of 8.0% to 8.8%.

One explanation for this finding may be that bisphosphonates remain active in bones for years after a person stops taking them.

An accompanying comment suggests that, until more research is available on long-term bisphosphonate use, doctors follow these recommendations based on T scores (in this measurement of bone density, a score below -1.0 means you have low bone density. Anything under -2.5 is considered osteoporosis):

• People with low bone-mineral density at the femoral neck of the hip (a T score below -2.5) after taking a bisphosphonate for three to five years, and those with existing spine fractures and T scores below -2.0, may benefit from long-term bisphosphonates.
• People with femoral neck T scores above -2.0 who are at low risk for spine fracture are not likely to benefit from extended use.

What should you do?

What should you take away from the FDA’s analysis? “People need to weigh the risks and benefits of bisphosphonates and discuss the duration of treatment with their doctors,” Dr. Robb-Nicholson says.

Whether or not you stay on bisphosphonates, you need to take good care of your bones. Exercise is one of the most effective ways to keep bones strong. Incorporate this combination of exercises, which are described in Osteoporosis: A Guide to Prevention and Treatment, a Special Health Report from Harvard Medical School.

Aerobic: Accumulate at least 150 minutes each week of moderate activity or 75 minutes of vigorous activity, or an equivalent mix of the two. Sustain activities for at least 10 minutes at a time.

Strength: Do strength exercises for all major muscle groups (legs, hips, back, chest, abdominals, shoulders, arms) at least twice weekly. Repeat each exercise eight to 12 times per set, aiming for two to three sets. Rest muscles for at least 48 hours between strength training sessions.

Balance: For older adults at risk for falls and others concerned about osteoporosis, include activities that enhance balance, such as tai chi or yoga, at least twice a week.

Flexibility: Stretching or other flexibility-enhancing exercises, preferably on days when you do aerobic or strength activities, or at least twice a week. Hold stretches for 10 to 30 seconds, repeating each stretch three to four times.