Ibandronate sodium is one bisphosphonate used to inhibit osteoclast-mediated bone resorption.
DR P. MARAZZI / sciencesource.com
CHICAGO—A 75-year-old woman with low bone density, who has had a fracture and has other risk factors for fracture, is treated with the bisphosphonate alendronate. After five years on the drug she comes back, wondering: Should I stop taking the drug?
She’s had no additional fractures. Her bone density has improved, but her lumbar spine T score is still a bit above the treatment threshold. Her turnover markers are both low, consistent with the effects of the bisphosphonate treatment.
“Like many [osteoporosis patients], she’s worried about the side effects of her medicine,” said Kenneth Saag, MD, MSc, professor of medicine at the University of Alabama School of Medicine, who presented the case at the ACR’s State-of-the-Art Clinical Symposium in April.
It’s difficult to know just what to do in these scenarios, Dr. Saag said. It’s “become the most contentious topic in the bone field—how long to treat, and who should we consider [giving] a break from therapy?”
Calling this a “crisis,” Dr. Saag described how bisphosphonate use has been declining at a fast rate—appropriately in some cases, but other patients have simply stopped the drug without talking to a doctor.
“We have a 50% decline in our use of bisphosphonates from when it peaked in the mid-2000s,” he said.1 After a fracture, only 20% of people are identified and treated—and that number is declining.2
At the same time, what had been a decline in hip fracture rate has begun to plateau.
The potential opportunity for a drug holiday in some patients is clear, Dr. Saag said. Bisphosphonates bind to bone, and when a patient stops using them after 10 years of treatment, they lose an estimated 2.5 mg per day.
“This is not like many drugs we use,” he said.
A long-term extension of a fracture intervention trial found that those rerandomized to five more years of alendronate treatment or five years of placebo showed maintenance of bone density and very similar fracture risks for the two groups.3
But other analyses have found that the risk of benefit in terms of hip and vertebral fracture prevention tends to far outweigh the risk of an atypical fracture brought about the drug. The risk increases with longer duration of use.
Dr. Saag emphasized that although a drug holiday may be a good idea for some patients on bisphosphonates, other drugs should not be considered for a holiday.
The U.S. Food & Drug Administration has issued guidance, saying that although the optimal duration isn’t known, discontinuation should be considered after three to five years for patients with a low fracture risk.
“We want to use the drugs when we need them the most, and that’s changed our practice patterns a little bit,” Dr. Saag said. “We’re often saving these drugs [for patients in their] 60s, 70s and 80s instead of their 50s and 60s. We’re thinking about things like raloxifene, or even estrogen, earlier on. And we may have some new treatments on the horizon.”
Data on the impact of drug holidays on fracture risk conflict in observational studies, and it will likely be difficult to do randomized, controlled trials at this point because so few of today’s patients are on bisphosphonates for a long period of time, Dr. Saag said.
One group of experts recommended in a 2016 paper that—for postmenopausal women treated with oral bisphosphonates for at least five years or the IV form for three years—a drug holiday shouldn’t be considered unless they’ve had no hip, spine or other osteoporosis fractures before or during treatment; they have no bone mineral density T score of -2.5 or higher; and they are not a high fracture risk.3
But if a drug holiday is started, when should it be stopped?
“We don’t know when to restart,” Dr. Saag said. “We follow turnover markers. We look at bone density. We look at other risk factors, and we make a determination based on our best clinical judgment.”
Rather than a drug holiday, Dr. Saag said that, for some patients, he prefers the idea of a drug sabbatical, a period off the drug while other options are considered, rather than an indefinite time off bisphosphonates.
“Maybe we’ll get more evidence and, while we [explore options], I like the idea better of a sabbatical. Let’s not take a holiday, but let’s take a sabbatical and think about other things we might do in the meantime. … We could look at loss of BMD [bone mineral density] while on therapy. We could look at persistent turnover. Those would be things that might also influence our thinking.”
Other drugs could be considered as well, such as anabolics, denosumab, and raloxifene, all of which come with their own benefits and risks.
Dr. Saag emphasized that although a drug holiday may be a good idea for some patients on bisphosphonates, other drugs should not be considered for a holiday. “When you stop many of our drugs—when you stop estrogen, when you stop raloxifene, and when you stop denosumab—you lose bone rapidly,” he said. “So the idea of taking a break from these drugs is different than taking a break from bisphosphonates.”
Thomas R. Collins is a freelance writer living in South Florida.
References
- Wysowski DK, Greene P. Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012. Bone. 2013 Dec;57(2):423–428.
- 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 Sep;29(9):1929–1937.
- Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: The Fracture Intervention Trial Long-Term Extension (FLEX): A randomized trial. JAMA. 2006 Dec 27;296(24):2927–2938.
- Adler RA, El-Hajj Fuleihan G, Bauer DC, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016 Jan;31(1):16–35.
