The issue of bisphosphonate holidays has again been raised by US researchers who found that therapy beyond five years was not associated with lower risk of hip fracture in postmenopausal women.

In an observational study involving 29,685 women who took bisphosphonates for five years, there was no difference in hip fracture risk among those who discontinued treatment compared to those who continued for a further five years.

There was some suggestion that continuing for two extra years after the initial five years of treatment might be associated with lower fracture risk than five years, but this would need to be confirmed in other studies, said researchers from the Kaiser Permanente healthcare group.

The cohort study analysed outcomes for postmenopausal women (median age 71 years) who were enrolled in the Kaiser Permanente California healthcare system and had taken oral bisphosphonates for five years.

During follow up of a further five years there were 507 incident hip fractures identified.

However over that period there were no differences in the cumulative incidence (ie, risk) of hip fracture if women remained on bisphosphonate therapy for two additional years (five-year risk difference [RD], −2.2 per 1000) or for women who continued therapy for five additional years (5-year RD, 3.8 per 1000 individuals).

There was a suggestion of lower fracture risk for an extra two years versus five years but this was not statistically significant and the numbers were small.

Writing in JAMA Network Open, the researchers said few trials had studied the effects of bisphosphonates extending beyond five years of treatment and the evidence available was weak and contradictory.

They cited the example of the five-year FIT trial extension (FLEX) involving 1099 women that found no greater overall fracture risk for most clinical fractures in women who stopped alendronate after three to five years compared with those continuing to 10 years – except for clinical vertebral fracture risk reduction but not those measured radiographically.

Likewise findings from a risedronate study had led to suggestion that bisphosphonate continuation beyond five years may afford fracture protection in higher risk women, but again the numbers in the study were small.

“The association of discontinuation at two years and other points with fracture risk should be further studied in randomised clinical trials. Future investigation should also examine whether such findings apply to women at higher or lower fracture risk and to what degree other fracture outcomes might be affected,” they concluded.