Following Patients With Osteoporosis During Bisphosphonate Drug Holidays

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A recent study aimed to determine the clinical and laboratory parameters associated with increased fracture risk in patients on holidays from taking bisphosphonates (BP) for osteoporosis.

Bisphosphonates (BP) are one of the most common types of drugs prescribed to treat osteoporosis, but prolonged therapy has been associated with rare adverse events, specifically atypical femoral fractures and osteonecrosis of the jaw. As a result, drug holidays from BPs have become standard practice, although there are minimal data on the optimal duration of these holidays.

A recent study aimed to determine the clinical and laboratory parameters associated with increased fracture risk in patients on BP drug holiday. The study was a continuation of a prior project, which concluded that clinical fractures occurred early during the holiday and in patients with lower bone mineral density (BMD) and/or older age at the start of holiday.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) guidelines from 2016 recommend a holiday after 5 years of oral and 3 years of intravenous BP treatment for patients with moderate fracture risk and after 10 years of oral and 6 years of intravenous BP treatment for patients at higher fracture risk.


Researchers conducted a retrospective chart review of 401 patients with osteopenia or osteoporosis who began a BP drug holiday from 2004 to 2013. Collected parameters included demographics, prior therapy, BMD, bone turnover markers, parathyroid hormone, calcium and vitamin D status, and clinical reports of fractures.

Sixty-two, or 15.4% of patients, developed a fracture during follow-up. The yearly incidence of fractures ranged from 3.7% to 9.9%, peaking at 9.9% and 9.8% during years 4 and 5, respectively.

The majority of fractures occurred at the wrist, foot, ribs, and spine.

The mean age of the fracture group was higher than the nonfracture group, though not significantly different (69.24 ± 12.26 years vs.66.42 ± 10.18 years; P = .09). Compared to the nonfracture group, the fracture group had lower femoral neck BMD (0.75 ± 0.12 g/cm2 vs. 0.79 ± 0.10 g/cm2; P = .03) and T-scores (—2.13 ± 0.99 vs. –1.78 ± 0.79; P = .01) at baseline.

The average duration of BP therapy prior to holiday was 6.34 ± 3.23 years, ranging from 6 months to 30 years. Prior to holiday, 61.6% of patients were on alendronate, 34.3% of patients were on risedronate, 13.3% on ibandronate, and 6.91% on zoledronic acid. These specific drug therapies did not affect fracture rates (all P >.50).

The researchers said the current practice of BP drug holidays needs further assessment in terms of their initiation and length. Patients who begin drug holidays at high risk for fracture based on BMD, age, or other clinical risk factors need close follow-up during the holiday, especially as its duration lengthens. Fracture risk needs to be regularly assessed and treatment resumed accordingly, they wrote.


Bindon B, Adams W, Balasubramanian N, Sandhu J, Camacho P. Osteoporotic fractures during bisphosphonate drug holiday. Endocr Pract 2018;24(2):163-169. doi: 10.4158/EP171975.OR