With the launch of the first prescription osteoporosis medication 15 years ago, millions of Americans with the bone-thinning disease began taking the drugs and never looked back.
But now many bone-health doctors are looking back and becoming increasingly uneasy.
In the past few years, evidence has emerged that long-term use of osteoporosis drugs — particularly the oldest class of drugs, the bisphosphonates — may do more harm than good. Some doctors are starting to tell at least some of their patients to stop taking the drugs for a time, to take a "drug holiday."
That strategy is a tough sell for consumers who have been bombarded with osteoporosis medication advertisements for years.
When osteoporosis drugs first came out, "people thought, this is a recurring disease, like high blood pressure. So why wouldn't you treat it for the rest of their lives?" said Dr. Richard Eastell, an expert in bone metabolism at the University of Sheffield in Britain who spoke about the issue late last year at the annual meeting of the American Society for Bone and Mineral Research. "But there are now some anxieties with long-term use."
REASONS FOR CAUTION
Several factors are merging to usher in a new era of caution surrounding the medications. One is the simple acknowledgment that some people are approaching 10 to 15 years of continuous use.
"Worldwide, it's a commonly discussed question as to how long you should go on with these treatments," Eastell said. "Beyond 10 years, we have no knowledge of how these treatments work."
Added to that, several potential risks from long-term use have recently arisen.
In rare cases, people taking bisphosphonates — which include Fosamax, Boniva, Actonel and Reclast — can develop jaw necrosis, a condition in which the jawbone begins to deteriorate. And a study published in September in BMJ, the British Medical Journal, found that people who take bisphosphonate drugs for several years have a slightly higher risk of developing esophageal cancer.
Experts don't know why the drugs would increase the cancer risk, although the drugs have been known to irritate the esophagus in some people.
Of most concern, however, is that long-term bisphosphonate users can develop rare and unusual fractures in the thigh bone, or femur. A 2008 study first linked long-term use of the medications to femur fractures, and other research has confirmed the link. On Oct. 13, the Food and Drug Administration announced it will now require bisphosphonate drugs to carry information on their labels describing the risk of rare femur fractures.
Without a lot of clear scientific evidence to guide them, doctors are debating how long people should take bisphosphonates and whether occasional drug holidays are a good idea.
HOW BISPHOSPHONATES WORK
Bones grow and change. After reaching peak bone mass in the early or mid 20s, bone density begins to decline because old bone is lost faster than new bone is made. This process speeds up in midlife, especially after menopause in women.
Bisphosphonates work by preventing the body from reabsorbing bone. They slow bone loss but also interfere with the natural bone-remodeling cycle, the process by which old bone is continually broken down and new bone is fashioned to replace it. This interference, it's thought, lies behind the unusual fracture risk. And some bone specialists think that leaving bones free of drugs for a year or more in people with osteoporosis allows the bone-remodeling process to kick in again.
Drug holidays may also be justified, these specialists say, because bisphosphonate medications remain in bone tissue for a year or two after people stop taking them. "To give high doses indefinitely is not what you want to do," said Dr. Ian Reid, an endocrinologist and bone expert at the University of Auckland in New Zealand. "After five years, it's a good time to reassess. If the bones don't show osteoporosis, we typically stop the drug and monitor bone density.''
Doctors are pulling back from prescribing osteoporosis medications for people who have some bone loss but do not meet the diagnostic criteria for osteoporosis, said Dr. Felicia Cosman, clinical director of the National Osteoporosis Foundation. This milder condition is sometimes referred to as osteopenia.
"It's ironic that many of these cases of femur factures were in women with mild bone loss who probably should not have been on these drugs," Cosman said. "We probably used too many bisphosphonates in too many women for too many years. But it's not that we should stop it in everyone. The therapy has to be individualized."
The osteoporosis drug market was valued at $9.6 billion last year and is expected to double within 10 years.
Still, under-use of osteoporosis drugs remains a bigger problem than overuse, Cosman said. One large study of osteoporosis patients found almost half had stopped taking their medications within a year after diagnosis.
"It's been difficult to convince people to take drugs," she said. "Now some are more skeptical that these drugs are providing the benefits that we said they did. We need to be clear that a two- to five-year course of these drugs saves fractures, pain, disability and life. There is just no question about that."