— Study compared hip fractures after 5 years, 7 years, and 10 years

by Kristen Monaco, Staff Writer, MedPage Today December 7, 2020

Women got no extra protection against hip fracture from staying on oral bisphosphonates beyond 7 years, researchers reported.

In a retrospective cohort study of nearly 30,000 women who completed 5 years of oral bisphosphonate treatment, those who continued therapy for an additional 5 years didn’t see a significant difference in cumulative incidence of hip fracture versus women who only stayed on therapy for 2 additional years, Monika Izano, PhD, of Kaiser Permanente Northern California in Oakland, and colleagues wrote in JAMA Network Open.

Looking at 5-year risk differences, those who remained on therapy for only 2 additional years actually saw a small decrease in the cumulative incidence of hip fracture (-2.2 per 1,000 individuals, 95% CI -20.3 to 15.9), whereas those who stayed on a bisphosphonate for 5 more years saw a slight uptick in hip fracture incidence (3.8 per 1,000 individuals, 95% CI -7.4 to 15.0).

Overall, the 5-year cumulative hip fracture incidences were as follows:

• Discontinued after initial 5 years: 23.0 hip fractures per 1,000 individuals
• 6-month holiday plus 2 additional years: 20.8 per 1,000 individuals
• Continued for 5 additional years: 26.8 per 1,000 individuals

“While our results suggest that interruption of bisphosphonate treatment after approximately 2 additional treatment years may be associated with lower interim risk of hip fracture compared with women who continued bisphosphonate treatment for 5 additional years, the 5-year risk differences were not statistically significant and the numbers of women and hip fracture events in this exposure group were relatively small,” the group explained.

Nonetheless, they added that this “potential hip fracture benefit for continuing 2 additional years but not for 5 additional years should be further studied,” as should whether this possible benefit is seen specifically among women with high or low risk for fracture.

They noted that a Task Force of the American Society for Bone and Mineral Research recommended in 2015 that low-risk patients should consider a bisphosphonate “drug holiday” after 5 continual years of treatment. But on the other hand, women at high risk for fracture should continue with ongoing treatment.

But benefits beyond 5 years of continued treatment remain largely a mystery, Izano’s group pointed out.

To further address these lingering questions, the group drew on data from 29,685 women ages 45 to 80 (median age 71) from Kaiser Permanente Northern and Southern California. All women had initiated oral bisphosphonate therapy with alendronate (Binosto, Fosamax), risedronate (Actonel, Atelvia), or ibandronate (Boniva), and completed the initial 5 years of treatment from 2002 to 2014. Women who previously received intravenous bisphosphonates or etidronate were excluded.

After the initial 5 years of treatment, about 37% of women were identified as having osteoporosis. During the 5 years of follow-up after the completion of the initial 5 years of therapy, 507 incident hip fractures occurred.

The researchers noted that the rates of incident hip fracture were similar in both groups, whether or not the women took a 6-month “grace period” of discontinuation in between their initial 5 years of therapy and continuation of therapy.

Overall, Izano’s group pointed out that these findings are reflective of the 2006 FLEX randomized clinical trial, which found that overall fracture risk wasn’t significantly different between women who took alendronate versus placebo for 5 additional years after an initial 5 years.