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Bone fracture risk rises during ‘drug holidays’

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May 16, 2018

Pauline M. Camacho, MD, FACE
Pauline M. Camacho

Approximately 15% of patients with osteoporosis who stop taking bisphosphonates experience bone fractures, according to study results published in Endocrine Practice.

“The study shows that osteoporotic fracture risk increases during bisphosphonate holidays,” Pauline M. Camacho, MD, FACE, professor of medicine, division of endocrinology and metabolism at Loyola University Medical Center and director of Loyola University Osteoporosis and Metabolic Bone Disease Center, told Endocrine Today. “Patients should be followed closely, and the duration of therapy needs to be tailored based on their risk. Within the first few years of being off drug, the risk of fragility or osteoporotic fractures will expectedly increase.”

Researchers conducted a retrospective chart review of 401 patients with osteoporosis or osteopenia (371 women; mean age, 67 years; 92.6% white) who discontinued bisphosphonate drugs (beginning a “drug holiday”) between 2004 and 2013 at Loyola University Osteoporosis and Metabolic Bone Disease Center. Patients had previously taken bisphosphonates for an average of 6.3 years. Researchers considered patients’ demographics, history of therapy, bone mineral density, bone turnover markers, calcium and vitamin D status, and reports of fractures. This information came from electronic medical records, which researchers examined at the beginning of the drug holiday, twice yearly for the first 2 years and then annually.

Researchers found that 10 participants experienced a fracture prior to a drug holiday and were not included in the analysis, 62 experienced fractures after beginning the drug holiday, and 329 experienced no fractures. The highest incidence of fracture was at years 4 and 5 (9.9% and 9.8%, respectively). Participants who experienced fracture were older than those who did not (mean age, 69.24 years vs. 66.42 years; P = .09). The most common sites of fracture were the wrist, foot, rib and spine.

Physicians must monitor patients with osteoporosis who temporarily discontinue their bisphosphonate therapy, according to Camacho.

“These patients should be instructed to take fall precautions, and to report any fractures to their physician, as this would often lead to resumption of therapy,” Camacho said. – by Melissa J. Webb

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Pauline M. Camacho, MD, FACE, can be reached at

Disclosures: The authors report no relevant financial disclosures.

itj+ Perspective

Annette L. Adams

It was with great interest that I read the recently published study by Bindon and colleagues on osteoporosis-related fractures during bisphosphonate drug holiday. This is an important and timely topic, as clinicians and patients struggle to maximize osteoporosis-related fracture reduction and minimize adverse events, such as atypical femur fractures, with bisphosphonate drug holidays thought to be a viable strategy for achieving that balance.

In a large case-series of patients with osteoporosis who cease bisphosphonates, the authors observed that 15% of patients sustained fractures during the holiday period. Further, the authors state that the incidence of fractures increased annually, with the highest rates in years 4 and 5 of the holiday. This would suggest that fracture risk does change over time during holiday and that lengthier holidays may be riskier for some patients. Additionally, the authors examined several potential risk factors for fracture among the holiday group compared with the non-fracture patients and found that femoral neck BMD and T-scores were significantly lower for the fracture group.

The study, however, raises a question, the answer to which would help better illuminate this issue of fracture risk during holiday. We are missing information about how common fractures are among the bisphosphonate-exposed group who continue therapy and do not go on holiday. That is, what is the background rate of fractures among bisphosphonate continuers, and how does the rate among drug holiday patients compare? This comparison is critical to understanding the true magnitude of the risk for the holiday group, as we cannot say that holiday patients are at increased risk for fracture without this comparison with non-holiday patients.

Regardless of the limitations of the study, the conclusions are important and remain valid — that drug holiday may not be appropriate for all patients, that drug holiday patients need to be heedful of fall prevention strategies, and that those who do undertake a drug holiday should be monitored carefully for changes in fracture risk as holiday duration lengthens.

Annette L. Adams, PhD, MPH

Research Scientist
Dept. of Research and Evaluation
Kaiser Permanente Southern California

Disclosure: Adams reports that she has received research funding from Amgen, Merck and Radius Health.