April 24, 2019
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Osteoporosis Drugs: Risks vs. Benefits

by Stephanie Watson  

If you’re female, you stand a one in two chance of breaking a bone due to osteoporosis, estimates the National Osteoporosis Foundation. Osteoporosis, a serious condition that thins and weakens bones, can make your bones so fragile that they can’t withstand a minor fall or even a cough. Major fractures can have long-term consequences, especially for older adults: A hip fracture, for instance, can lead to permanent loss of mobility and independence and a greater likelihood of early death.

Despite having a high fracture risk, many women with low bone density avoid taking bisphosphonates—the very drugs that could prevent bone loss and disability. One reason may be that some of bisphosphonates’ potential but rare side effects have come under negative, but often misguided, publicity over the past decade.

A note about men and osteoporosis: About one-third of all osteoporotic hip fractures worldwide occur in men, who are more likley than women to die the year after such a fracture. Male smokers and those with the lung condition chronic obstructive pulmonary disease (COPD) are at especially high risk. Yet men are far less likely to be assessed for bone loss and treated.

A game-changer

Bisphosphonate drugs help preserve bone mass by slowing down bone resorption—the breakdown of old bones. They’re incredibly effective drugs, reducing the risk of hip fractures by up to 50 percent and spine fractures by up to 70 percent.

Bisphosphonates are the first-line drug therapy for women with osteoporosis at high risk for fractures. They’re also approved for osteoporosis prevention in women with osteopenia (low bone mass, but not low enough to be diagnosed with osteoporosis) at high fracture risk. Bisphosphonates include alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), and zoledronic acid (Reclast, Zometa, Aclasta). They’re taken orally either once a day, once a week, or once a month, except for zoledronic acid, which is administered intravenously once every one to three years.

The number of bisphosphonate prescriptions soared between 1996, when they were introduced, and 2006. Then, between 2008 and 2012, use of these bone-strengthening drugs dropped by about half. Although this plunge could have partly been the result of better prescribing due to more accurate fracture risk assessment, it did coincide with media reports of two rare but serious bisphosphonate side effects, according to an analysis published in June 2018 in JAMA: The Journal of the American Medical Association.

Fears over side effects may lead many women who need these drugs to skip them. An international study published in 2012 found that more than 80 percent of postmenopausal women with fragility fractures weren’t being treated with bisphosphonates or other osteoporosis medications. It’s unclear how many women weren’t taking them for fear of potential complications.

The roots of drug fears

The bisphosphonate risks that have raised concerns are atypical femur fractures and osteonecrosis of the jaw. What makes an atypical femur fracture so frightening is that the femur, or thighbone, is the strongest bone in your body. Typically, it takes a lot of force—think a car accident or steep fall—to break it. Atypical femur fractures happen with little to no force. The bone snaps during everyday activities like walking, twisting, or even standing still.

The other risk—osteonecrosis of the jaw—happens when the jawbone is starved of blood, begins to die, and may become exposed inside the mouth. It’s more common in cancer patients who take high doses of bisphosphonates intravenously to prevent chemotherapy-related bone loss and in people who’ve had oral surgery.

It might seem ironic that drugs meant to strengthen bones can lead to fractures. Yet it makes sense, given that bisphosphonates work by suppressing the action of osteoclasts—cells that reabsorb and remove old and damaged bone. By slowing bone turnover, bisphosphonates may prevent your body from repairing any hairline cracks that form in the femur or jawbone.

Putting the risks into perspective

The absolute risk—or the true chance you’ll develop an atypical fracture while on these drugs—is extremely low, according to the JAMA analysis. In any given year, only 0.003 to 0.05 percent of people who take bisphosphonates will have this side effect—meaning that well over 99 percent won’t sustain an atypical fracture. Osteonecrosis of the jaw is even rarer, affecting an estimated 1 in 10,000 to 1 in 100,000 people who take them each year.

In contrast, fractures caused by osteoporosis are all too common. More than 860 out of 100,000 women with osteoporosis who go untreated will fracture a hip or femur in any given year. To put this in other terms, treating 1,000 women with bisphosphonates for three years might cause one atypical femur fracture but prevent 100 osteoporosis-related fractures. Taking bisphosphonates can also dramatically reduce your risk of having a second fracture and premature death.

Before taking bisphosphonates, discuss your risks with your doctor. Atypical femur fractures are more common (though still rare) in people of Asian ethnicity, which might suggest a genetic predisposition. Cancer treatment, diabetes, gum disease, steroid use, and smoking are risk factors for osteonecrosis of the jaw. If you take bisphosphonates, stay alert for side effects. An atypical fracture can cause dull or aching thigh or groin pain. Osteonecrosis of the jaw leads to pain, swelling, or a heavy feeling in the gums or jaw. If you have those symptoms, see your doctor.

This article first appeared in the September 2018 issue of UC Berkeley Health After 50.

Also see Osteopenia: What to Do About Bone Loss.