Beta-blocker exposure is associated with nonunion in a geriatric cohort of 253,266 extremity fractures

Abstract

Previously published animal studies have shown positive skeletal effects with local or systemic administration of beta blockers (BBs). However, population studies have shown mixed effects on bone mineral density (BMD) and fracture risk with BB use. The goal of this study was to evaluate whether exposure to BB is associated with fracture nonunion. Fee-for-service Medicare beneficiaries with an extremity fracture were identified by International Classification of Diseases (ICD)-10 and current procedural terminology (CPT) codes from 2016-2019. Charlson Comorbidity Index (CCI) was assigned using diagnoses prior to index fracture and nonunion identified by ICD-10 or CPT codes within one year from index fracture diagnosis. Patients were classified by BB exposure based on Part D (Pharmacy) claims between 90 days prior to and one year following index fracture. Chi square and Student T-tests were performed on categorical and continuous variables, respectively. Logistic regression was performed to evaluate the association between BB use and nonunion, controlling for age, sex, race, and comorbidity. Total number of fractures meeting inclusion criteria was 253,266 with 45% of patients having used a BB during the study period. The incidence of nonunion was 3.9% overall. BBs were associated with a 13% increase in non-union for all fracture types, after controlling for age, sex, fracture location, and CCI (OR 1.13 [CI 1.06-1.20], p<.001). Results of this study suggest a negative influence of BB on bone healing, contrary to results of previously published animal models and epidemiologic observations, and demonstrate that BB use during fracture care is associated with significant increase in incidence of nonunion.

Increased β 2 -adrenergic signaling promotes fracture healing through callus neovascularization in mice

“…Although these data identify the cell surface receptor ADRB2 as a promising target for promoting bone healing, they also suggest that its blockade may result in impaired fracture healing. Our observation that the nonselective βblocker propranolol caused delayed fracture healing in adult mice is supported by the Steffenson et al (59) study reporting a moderate association of βblocker exposure with nonunion in 253,266 fracture cases. Given these findings and recent demographic trends, with >22% of people aged 60 years or older taking βblockers (60), it is reasonable to examine the impact of this class of drugs on fracture nonunion in humans in more depth.…”