Risk of subtrochanteric and femoral shaft fractures due to bisphosphonate therapy in asthma: a population-based nested case–control study

Summary Concerns have been raised over the association between bisphosphonates and atypical fractures in subtrochanteric and femoral shaft regions, but the potential risk of these fractures due to bisphosphonate use in asthma has not been examined. Introduction Bisphosphonates are used as first-line treatment for osteoporosis; however, concerns have been raised over their association with atypical subtrochanteric (ST) and femoral shaft (FS) fractures. The potential risk of atypical ST/FS fractures from bisphosphonate use in asthma has not been examined. Methods A nested case–control study was conducted using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we identified patients with atypical ST/FS fractures and sex, age, and practice-matched controls. Conditional logistic regression was used to determine the association between bisphosphonate exposure and atypical ST/FS fractures. Results From a cohort of 69,074 people with asthma, 67 patients with atypical ST/FS fractures and 260 matched control subjects were identified. Of the case patients, 40.3% had received bisphosphonates as compared with 14.2% of the controls corresponding to an adjusted odds ratio (aOR) of 4.42 (95%CI, 2.98 to 8.53). The duration of use influenced the risk with long-term users to be at a greater risk (> 5 years vs no exposure; aOR = 7.67; 95%CI, 1.75 to 33.91). Drug withdrawal was associated with diminished odds of atypical ST/FS fractures. Conclusion Regular review of bisphosphonates should occur in patients with asthma. The risks and benefits of bisphosphonate therapy should be carefully considered in consultation with the patient. To improve AFF prevention, early signs which may warrant imaging, such as prodromal thigh pain, should be discussed.