The research was presented recently at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting. Bisphosphonates are a class of antiresorptive drugs that have been shown to slow bone loss and decrease fracture risk in osteoporosis patients.
In a 2013 report in the New England Journal of Medicine, FDA researchers noted that rare but serious adverse events were associated with bisphosphonates, such as atypical femur fractures, osteonecrosis of the jaw, and esophageal cancer, leading to a systematic review of long-term bisphosphonate efficacy. Based on the findings, FDA advisory committees reached a consensus that no regulatory restriction on duration of drug use should be put into place, although the labeling should be updated.
University of Alabama Birmingham researchers who conducted the recent population-based cohort study point out that, whatever the intentions, FDA warnings appear to have made drug holidays more common for bisphosphonates. Their study looked at the effects on hip fracture risk of discontinuing bisphosphonates among women who are long-term users of the osteoporosis therapies.
To do that, they employed Medicare data from 2006 to 2014 to identify 156,236 women who were long-term, adherent users of bisphosphonates, defined as being at least 80% adherent for 3 or more years. For those women, who had a mean age of 78.5 years, the most common bisphosphonates used were alendronate and zoledronic acid.
During a median follow-up period of 2.1 years, 40.1% of those patients stopped bisphosphonate therapy for at least 6 months or more, with 12.7% restarting a bisphosphonate later. Using that data, researchers calculated crude rates of hip fracture for those continuing bisphosphonate therapy and those who took a drug holiday, as well as for the length of the drug holidays.
“Our goal was to evaluate the risk of discontinuing therapy based on the length of the holiday, controlling for any possibly confounding factors, such as race, median income, rural or urban location, DXA scores or comorbidities,” explained lead author Jeffrey Curtis, MD, MS, MPH, William J. Koopman Endowed Professor in Rheumatology and Immunology at the UAB.
With 3,745 hip fractures occurring during follow-up, results indicate that hip fracture rates were lowest among the women who continued bisphosphonates but gradually increased as the length of the drug holidays increased. For example, women who took a drug holiday of more than 2 years showed the highest rate of hip fractures and had a significantly increased risk for hip fracture of up to 39%, compared with those who continued bisphosphonate use.
“While the notion of a drug holiday has become commonplace in osteoporosis management, there’s a dearth of evidence on when we should consider restarting bisphosphonate therapy,” Curtis pointed out. “The study’s findings may provide useful evidence to help guide rheumatologists as they plan long-term therapy for their patients dealing with low bone mass.”