In the Journals Plus

Bisphosphonate holiday may decrease fracture risk in women

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March 14, 2018

Women on bisphosphonates for at least 3 years who took a drug holiday for at least 12 months do not appear to have an increased risk for any osteoporosis-related fracture compared with women who persistently used bisphosphonates and those who were not adherent to persistent use, study data show.

Annette L. Adams, PhD, MPH, a research scientist in the department of research and evaluation at Kaiser Permanente Southern California in Pasadena, and colleagues compared women with a bisphosphonate holiday of at least 12 months (n = 11,497; mean age, 69.2 years; 59.5% white), women with persistent use with at least 50% adherence (n = 10,882; mean age, 70.7 years; 55.4% white) and women with non-persistent use with less than 50% adherence (n = 17,123; mean age, 71.2 years; 56.6% white) for incident osteoporosis-related fractures over 4 years.

During follow-up, the bisphosphonate holiday group was less likely to sustain an atypical femoral fracture compared with the other two groups (0.03% vs. 0.15%). The fracture rate per 1,000 person-years was lowest in the bisphosphonate group (28.8 per 1,000 person-years) compared with the non-persistent user group (43 per 1,000 person-years; rate ratio = 1.5; 95% CI, 1.36-1.65) and the persistent user group (32.8 per 1,000 person-years; rate ratio = 1.14; 95% CI, 1.06-1.23).

After accounting for FRAX score, modified Falls Risk Assessment Tool score, Quan-Charlson comorbidity score and prior/concomitant use of antisecretory medications, statins, thiazolidinediones and estrogens, the bisphosphonate holiday group compared with the persistent user group was less likely to have any osteoporosis-related fracture (HR = 0.92; 95% CI, 0.84-0.99) or vertebral fracture (HR = 0.83; 95% CI, 0.74-0.95); however, no difference was observed for the risk for hip fractures. After adjustment, the bisphosphonate group compared with the non-persistent user group was less likely to have an osteoporosis-related fracture (HR = 0.71; 95% CI, 0.65-0.79), hip fractures (HR = 0.59; 95% CI, 0.5-0.7) or vertebral fractures (HR = 0.68; 95% CI, 0.59-0.78).

Among participants with prior fracture, the risk for any fracture was lower in the bisphosphonate holiday group compared with the persistent user group (HR = 0.79; 95% CI, 0.67-0.94). Further, the bisphosphonate group compared with the non-persistent user group had decreased risks for any fracture (HR = 0.65; 95% CI, 0.52-0.8) and hip fracture (HR = 0.44; 95% CI, 0.27-0.75). Among participants without prior history of fracture, the bisphosphonate holiday group had a lower risk for vertebral fracture compared with the persistent user group and lower risks for any fracture, hip fracture and vertebral fracture compared with the non-persistent user group.

“While it may be possible that women on [bisphosphonate] holiday eventually lose some fracture protection, our findings suggest that they are not at increased risk for fracture compared to persistent users,” the researchers wrote. “Future efforts could develop more detailed risk scores to assist physicians in identifying patients for whom [bisphosphonate] discontinuation may be appropriate (or inappropriate) to assist patients and health care providers in making choices about bisphosphonate use.” – by Amber Cox

Disclosures: Adams reports she received research support from Amgen and Merck for work not related to this study. No other authors report relevant financial disclosures.