Study Finds Common Osteoporosis Drug Does Not Raise Risk of Femur Fracture
Taking the osteoporosis drug alendronate (
Fosamax
) for a decade or more doesn’t appear to increase the risk of rare femur (thighbone) fractures (also known as atypical femoral fractures), according to a new Danish study. The findings, published in May in
The BMJ,
contradict other research, which has found an association between thighbone fractures and long-term treatment with a class of osteoporosis drugs called bisphosphonates.
Bisphosphonates, which include alendronate as well as risedronate sodium ( Actonel ), ibandronate ( Boniva ) and zoledronic acid ( Reclast ), are the most widely prescribed osteoporosis drugs. They’re intended to reduce fractures by slowing down the breakdown and resorption of bone, which is part of the normal cycle of bone turnover. But because of concerns they may increase the risk of atypical thighbone fractures, doctors often recommend a “drug holiday” for certain patients or, in some cases, stopping the drug altogether. Fear of these fractures and another rare side effect, osteonecrosis of the jaw, contributed to a 50 percent drop in bisphosphonate prescriptions in the United States in four years.
To determine the safety of long-term bisphosphonate use, Danish researchers analyzed registry data on nearly 62,000 patients taking alendronate for osteoporosis from 1996 to 2007. Of these, 1,428 experienced thighbone fractures, but the researchers found the number of fractures did not increase with longer-term use.
Nearly 6,700 of the registry patients sustained hip fractures during the study period, but the risk declined over time to an overall 30 percent reduced risk at 10 years. The researchers concluded that because the number of thigh fractures was much lower than the number of hip fractures – and because hip fractures declined over time, while thighbone fractures didn’t increase – the benefits of taking alendronate outweighed the harms, even after many years of continuous use.
The researchers also found that thighbone fractures were higher in patients with comorbid conditions, including diabetes, and in patients who filled prescriptions for proton pump inhibitors; both of those have been found to be risk factors in previous studies.
Worldwide, osteoporosis causes about 1.5 million fractures each year – many of them debilitating and most of them in women. Men are also at risk, especially after age 70, but women are more vulnerable, in part because age-related bone loss accelerates when estrogen levels drop after menopause.
Rheumatoid arthritis (RA) is also a risk factor for fragile, thinning bones, increasing osteoporosis risk as much as 30 to 40 percent, even when aggressively managed. Corticosteroids, used to treat RA and other types of inflammatory arthritis, are also known to cause bone loss, and pain and disability can make it harder to get the exercise needed to keep bones strong.
Engaging in regular weight-bearing exercise (including walking), getting plenty of calcium and vitamin D, and not smoking are proven ways to improve bone health. Bisphosphonates play an important role, too, despite concerns over a higher risk of thighbone fractures, which this study addresses.
The study does have some limitations. For one thing, says rheumatologist Kenneth Saag, MD, a professor of medicine at the University of Alabama at Birmingham School of Medicine and an expert on the epidemiology of osteoporosis, the study uses data saved for billing purposes, rather than clinical records. That means there was no information about patient lifestyles – what they ate and whether they smoked, exercised or took calcium and vitamin D supplements. And because there were no X-rays, it was impossible for researchers to distinguish atypical fractures from more common ones.
“All that said, however, this is an important contribution,” Dr. Saag says. “I hope it leads patients and physicians to more critically consider the benefits versus the risks of these medicines to treat bone health. There are no drugs that don’t have side effects, and we are always trying to balance the benefits and harms. This study provides some important information to help judge that equation.”
Nancy Lane, MD, a professor of medicine and director of the Center for Musculoskeletal Health at the University of California, Davis Medical Center, is a noted authority on both osteoarthritis and osteoporosis. She agrees with Dr. Saag, saying, “The benefits of treating [patients with alendronate] for up to 10 years to reduce hip fractures is greater than any risk of [thighbone] fractures, so we stand behind this therapy long-term, if needed.”
Author: Linda Rath for the Arthritis Foundation
Bisphosphonates, which include alendronate as well as risedronate sodium ( Actonel ), ibandronate ( Boniva ) and zoledronic acid ( Reclast ), are the most widely prescribed osteoporosis drugs. They’re intended to reduce fractures by slowing down the breakdown and resorption of bone, which is part of the normal cycle of bone turnover. But because of concerns they may increase the risk of atypical thighbone fractures, doctors often recommend a “drug holiday” for certain patients or, in some cases, stopping the drug altogether. Fear of these fractures and another rare side effect, osteonecrosis of the jaw, contributed to a 50 percent drop in bisphosphonate prescriptions in the United States in four years.
To determine the safety of long-term bisphosphonate use, Danish researchers analyzed registry data on nearly 62,000 patients taking alendronate for osteoporosis from 1996 to 2007. Of these, 1,428 experienced thighbone fractures, but the researchers found the number of fractures did not increase with longer-term use.
Nearly 6,700 of the registry patients sustained hip fractures during the study period, but the risk declined over time to an overall 30 percent reduced risk at 10 years. The researchers concluded that because the number of thigh fractures was much lower than the number of hip fractures – and because hip fractures declined over time, while thighbone fractures didn’t increase – the benefits of taking alendronate outweighed the harms, even after many years of continuous use.
The researchers also found that thighbone fractures were higher in patients with comorbid conditions, including diabetes, and in patients who filled prescriptions for proton pump inhibitors; both of those have been found to be risk factors in previous studies.
What this means for you
Worldwide, osteoporosis causes about 1.5 million fractures each year – many of them debilitating and most of them in women. Men are also at risk, especially after age 70, but women are more vulnerable, in part because age-related bone loss accelerates when estrogen levels drop after menopause.
Rheumatoid arthritis (RA) is also a risk factor for fragile, thinning bones, increasing osteoporosis risk as much as 30 to 40 percent, even when aggressively managed. Corticosteroids, used to treat RA and other types of inflammatory arthritis, are also known to cause bone loss, and pain and disability can make it harder to get the exercise needed to keep bones strong.
Engaging in regular weight-bearing exercise (including walking), getting plenty of calcium and vitamin D, and not smoking are proven ways to improve bone health. Bisphosphonates play an important role, too, despite concerns over a higher risk of thighbone fractures, which this study addresses.
The study does have some limitations. For one thing, says rheumatologist Kenneth Saag, MD, a professor of medicine at the University of Alabama at Birmingham School of Medicine and an expert on the epidemiology of osteoporosis, the study uses data saved for billing purposes, rather than clinical records. That means there was no information about patient lifestyles – what they ate and whether they smoked, exercised or took calcium and vitamin D supplements. And because there were no X-rays, it was impossible for researchers to distinguish atypical fractures from more common ones.
“All that said, however, this is an important contribution,” Dr. Saag says. “I hope it leads patients and physicians to more critically consider the benefits versus the risks of these medicines to treat bone health. There are no drugs that don’t have side effects, and we are always trying to balance the benefits and harms. This study provides some important information to help judge that equation.”
Nancy Lane, MD, a professor of medicine and director of the Center for Musculoskeletal Health at the University of California, Davis Medical Center, is a noted authority on both osteoarthritis and osteoporosis. She agrees with Dr. Saag, saying, “The benefits of treating [patients with alendronate] for up to 10 years to reduce hip fractures is greater than any risk of [thighbone] fractures, so we stand behind this therapy long-term, if needed.”
Author: Linda Rath for the Arthritis Foundation
