The Osteoporosis Controversy, Part II: Are We Over-Treating?

April 4, 2018

Which patients need bisphosphonate therapy-and for how long?

The risk of using a medication in patients with milder disease is that the likelihood of harm can start to outweigh the benefits. That’s one of the arguments against aggressive treatment with bisphosphonates.

The debate particularly concerns women with osteopenia.

The problem is that bisphosphonates may increase bone density, but that doesn’t necessarily translate into decreased fracture rates, according to Susan Ott, MD, of the University of Washington. Furthermore, no long-term studies have weighed the benefits against the risks of using bisphosphonates to treat osteopenia.1

“Instead of preventing fractures you might get fractures,” Ott says. “But it doesn’t happen right away. It certainly doesn’t happen in the first 5 years [of treatment].”

Longer-term use of bisphosphonates has been linked to increased risk of atypical fractures of the femur and osteonecrosis of the jaw. Some trials, but not others, have also reported increased rates of atrial fibrillation.

Who needs treatment and for how long?
Research suggests treating osteoporosis can decrease vertebral fractures by 30% to 70%, but Teppo Järvinen, MD, of the University of Helsinki says the evidence is not so clear-cut.2 Evidence that supports the use of bisphosphonates to decrease hip fractures is limited to women aged 65 to 80 who already have osteoporosis. Meager evidence supports the benefit of treating women over age 80 and men of all ages. Furthermore, evidence from clinical trials does not necessarily transfer into real-world situations, according to Järvinen.

“Osteoporosis guidelines systematically ignore the obvious ‘evidence void’ in the RCTs . . . and instead extrapolate efficacy estimates derived from younger women to their older counterparts and even to men,” he writes.

But according to some researchers, the data are more clear-cut for individuals with osteoporosis who have already had a fracture.

“Among doctors/the scientific community, a clear consensus exists that patients with hip fracture should be on osteoporosis medication, because they are at risk for further fractures. Studies show that starting bisphosophonates after a first hip fracture can decrease the risk of having a second,” Sundeep Khosla, MD, (Mayo Clinic College of Medicine, Rochester, MN) and Elizabeth Shane, MD, (Columbia University, New York, NY) wrote in an editorial in the Journal of Bone and Mineral Research.3

In 2016, the American Society for Bone and Mineral Research, the National Osteoporosis Foundation (NOF), and the National Bone Health Alliance (NBHA) called for more aggressive treatment in high-risk patients, and greater awareness of who needs treatment. The statement was largely based on a Finnish study suggesting that the risk for sustaining a second osteoporotic fracture in the first year after having a first fracture was triple that of the general population.4

“This new information makes it more important than ever that physicians and health care providers take immediate steps to evaluate and treat patients who have sustained an osteoporotic fracture,” Robert Gagel, MD, of M.D. Anderson Cancer Center, NOF President and NBHA Co-Chair, said in the press release.4

Yet a review of Medicare claims data for individuals who were hospitalized for hip fracture and were aged 50 years and over found that only 28.5% used osteoporosis medication 12 months after discharge. And, these rates have declined from 40% in 2002 to about 20% in 2011.5

Fear factor
The fear factor of an atypical fracture may be enough to keep many patients away. Is that fear founded?

Experts say that the benefits of treatment far outweigh the risks of sustaining an atypical fracture, with less than one event caused for every 100 fractures prevented.6

But that’s for treatment of up to 5 years. Some women with osteopenia are diagnosed in their fifties, and could face much longer time on therapy.

Research also suggests that the benefits of therapy may continue after drug discontinuation. So it would appear that the benefits outweigh the risks, but perhaps for a limited time, especially in those with mild bone thinning whose fracture risk may be relatively low.6

That may be why some experts recommend a drug holiday after 5 years on alendronate, and 3 years on zoledronic acid, at least in patients at low risk for fracture.6

The debate continues
“In my opinion, overstating the need to treat osteoporosis and downplaying the dangers of osteoporosis drugs together amount to a perfect storm of disease mongering. It is easy to exaggerate the effects of osteoporosis drugs, and maintain the fiction that vertebral fractures, which are rarely associated with any pain or other symptoms, are deadly and serious. Both of these are among the many tactics used to sell more drugs in the name of fracture prevention,” Teppo Järvinen said in Alix Spiegel’s NPR article.1

“There can be no more urgent call to action for our field than we face today. We must find ways to ensure that patients who need appropriate treatment for osteoporosis are not only prescribed effective medications, but are also equipped with the information they need to make an informed choice on taking these medications,” write Khosla and Shane.

References:

1. Spiegel A. How a bone disease grew to fit the prescription. NPR. December 21, 2009.

2. Järvinen TL, Michaëlsson K, Aspenberg P, et al. Osteoporosis: the emperor has no clothes. J Intern Med. 2015;277:662-673. doi: 10.1111/joim.12366.

3. Khosla S, Shane E. A crisis in the treatment of osteoporosis. J Bone Miner Res. 2016;31:1485-1487. doi:10.1002/jbmr.2888

4. Statement from American Society for Bone and Mineral Research, National Osteoporosis Foundation, and National Bone Health Alliance. Nation’s scientific and medical bone health experts call for action on dangers of not treating osteoporosis more aggressively. Accessed March 20, 2018.

5. Solomon DH, Johnston SS, Boytsov NN, et al. Osteoporosis medication use after hip fracture in U.S. patients between 2002 and 2011. J Bone Miner Res. 2014;29:1929-1937. doi: 10.1002/jbmr.2202.

6. Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016;374:2096-2097. doi: 10.1056/NEJMc1602599.