Therapeutic radiation directly alters bone fatigue strength and microdamage accumulation

Abstract

Radiotherapy (RTx) is an essential and efficacious oncologic treatment, however, post-RTx bone fragility fractures present a challenging clinical problem. Cancer survivors treated with RTx are at variable risk for these late-onset, complex fragility fractures. Little data exists regarding the effects of RTx on bone fatigue properties despite the likelihood of fatigue loading as a mechanism leading up to atraumatic fracture. In this study, femurs collected from adult male rats were irradiated ex vivo with a therapeutic dose of x-irradiation (20 Gy), and then fatigued using a three-point bend setup. Femurs positioned in an isotonic bath at room temperature were loaded to a range of prescribed initial strain levels (based on beam theory equations, prior to any fatigue damage) at 3 Hz in force control. The goals of this study were to determine the feasibility of assessing RTx-induced alterations in 1) femur fatigue strength, 2) structural microdamage (creep and stiffness), and 3) tissue damage (diffuse damage and/or linear microcracking). Mid-diaphyseal morphology and tissue mineral density were not different between the RTx and Sham groups (p ≥ 0.35). With increasing applied apparent strain, the number of cycles to failure was reduced for the RTx femurs when compared to the Sham femurs (treatment x ε_app, p = 0.041). RTx femurs had a greater phase II (steady state) creep rate (p = 0.0462) compared to Sham femurs. For femurs that reached 500k cycles, the RTx group had greater diffuse damage area (p = 0.015) than the Sham. This study provides evidence that radiation at therapeutic doses can directly diminish bone fatigue properties. This loss of fatigue properties is associated with increased structural fatigue damage and diffuse microdamage, without alterations in morphology or tissue mineral density, indicating a reduction in bone quality.