Presentation (CTI)

OBJECTIVES: Bisphosphonates (BP) are widely used to treat osteoporosis, bone cancer and hypercalcemia to reduce fracture risk. Observational studies have highlighted rare but serious adverse events (AE), such as atypical femoral fracture and osteonecrosis of the jaw (ONJ). While some meta-analyses have found evidence of publication bias, potential impact on results and conclusions was not explored. Clinical guidelines are often based on meta-analyses and published literature, which may bias medical decision-making. This study aimed to assess the presence and potential impact of publication bias in BP safety evaluations.
METHODS: Systematic reviews and meta-analyses of BP-related AE were searched. Odds ratios (OR) from original clinical studies were collected, and publication bias was assessed using funnel plots, Egger's tests, and robust Bayesian meta-analysis (RoBMA). The effect of bias was quantified by comparing unadjusted and adjusted pooled estimates using trim-and-fill and RoBMA.
RESULTS: The analysis included 42 systematic reviews totalizing 112 clinical studies (58% were observational) for 10 AE. Publication bias concerned 2 out of 10 AE, high risk of publication bias was detected for atypical femur fractures and ONJ. For these, bias inflated effect estimates by 40-45% and 47-67%, respectively, with associations with BP use disappearing after adjustment . No high risk of publication bias was found for eight other AE (atrial fibrillation, myocardial infarction, stroke, kidney dysfunction, esophageal, breast, gastric, and colorectal cancer).
CONCLUSIONS: High risk of publication bias was detected for atypical femur fractures and osteonecrosis of the jaw, with associations with bisphosphonates use disappearing after adjustment. This bias may lead to a distorted assessment of the risk-benefit balance.