MONTREAL -- Lengthy drug holidays among patients with osteoporosis using bisphosphonates resulted in significantly increased risks of subsequent hip fractures, a researcher reported here at the American Society for Bone and Mineral Research annual meeting.
For patients who had stopped taking alendronate or risedronate for more than 12 months, there was a 30-50% increased risk of hip fracture within the next 2 years, according to Kenneth Saag, MD, of the University of Alabama at Birmingham.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"Bisphosphonates remain our predominant osteoporosis therapeutic class used internationally. However, we know that given concerns about rare bisphosphonate side effects, particularly the atypical femoral fractures and jaw osteonecrosis, the idea of a drug holiday -- a temporary or permanent discontinuation of therapy -- has become increasingly common."
Despite this, there is limited evidence about these holidays and their effects on subsequent fractures.
"Most data we have are from extensions of large clinical trials such as the , and while this information is very useful, it suffers from limited sample size, low statistical power, and poor generalizability. So the benefits and risks of stopping these drugs and the optimal timing are unclear and constitute a major question in the bone field today," Saag said during a plenary session.
To address this uncertainty, he and his colleagues conducted a population-based cohort study of women with Medicare medical and pharmacy coverage who were at least 80% adherent to their bisphosphonate regimen before discontinuing treatment.
Among more than 74,000 women who had been on alendronate, there were 2,245 hip fractures, for an incidence rate of 13.1/1,000 person-years (HR 1.28, 95% CI 1.12-1.46), and among the 9,823 who had taken risedronate, there were 269 hip fractures, for an incidence rate of 13.8/1,000 person-years (HR 1.45, 95% CI 1-2.11). For the 13,885 who had received zoledronate, there were 367 hip fractures, for an incidence rate of 18/1,000 person-years, which was not a significant difference (HR 1.31, 95% CI 0.94-1.82). This may have reflected the smaller sample size with zoledronate, or it may suggest that different effects may depend on the bone avidity of the individual bisphosphonates, Saag explained.
For patients who had a previous fragility fracture, who numbered 6,914, there were 430 hip fractures, for an incidence rate of 37.4/1,000 person-years (HR 1.38, 95% CI 1.01-1.89).
Among patients who had taken alendronate and had drug holidays exceeding 4 years, the increase in subsequent hip fractures rose by up to 80%, Saag said.
Increased risks were not seen for vertebral or distal radius sites, which are less well characterized using administrative data.
"Overall, if you look at the 53% relative risk reduction in the FLEX study, our data would represent a near undoing of the benefit that might have been achieved with the previous use of alendronate," he said.
"The clinical implication might be that a long bisphosphonate drug holiday may not be appropriate for all patients and a holiday from oral bisphosphonates alendronate and risedronate of 2 to 3 years may be undesirable," he told ľֱ. "Drug holidays shouldn't be indefinite, especially for those bisphosphonates that stick less well to the bone."
Additional work is needed with longer follow-up and larger numbers to better understand the long-term effects of bisphosphonate discontinuation, he concluded.
A limitation of the study, he added, was a lack of information about why individual patients decided to take drug holidays.
Primary Source
American Society for Bone and Mineral Research
Curtis J, et al "The impact of bisphosphonate drug holidays on fracture rates" ASBMR 2018; abstract 1006.