Bisphosphonates and Risk of Subtrochanteric,Femoral Shaft,and Atypical Femur Fracture: Sensitivity and Trim and Fill Studies

Abstract

Objective: This study carried out sensitivity analysis and trim-fill analysis between bisphosphonates and subtrochanteric, femoral shaft, and atypical femur fracture. Methods: A random-effects model was used finally. Sensitivity, trim and fill, and publication bias analyses were done. Results: Under a random-effects model (I²=87.535), the Z-value=5.672, p-value of test of null<0.001. Bisphosphonate exposure was associated with an increased risk of atypical femur fracture (3.243 [95% CI 2.160-4.870]). When any study is removed, the remaining sensitivity analysis results are still significant. Trim and fill results show that two studies were missed. After filling them, a funnel plot of precision by log risk ratio was more symmetrical. Conclusion: This study suggests that (1) there is an increased risk of subtrochanteric, femoral shaft, and atypical femur fracture in bisphosphonate users; (2) any single study does not influence the total sensitivity; (3) two studies have been lost, theoretically.