Total-body irradiation produces late degenerative joint damage in rats

Abstract

Purpose Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. Materials and Methods 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV x-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. Results T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. Conclusions Late degenerative changes in articular cartilage and bone were observed after total body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage.

Effect of X-ray Irradiation on Articular Cartilage Mechanical Properties

“…Ionizing radiation is known to lower proteoglycan content and compressive stiffness [8,[22][23][24][25]. Previous studies display that reactive oxygen radicals induced by ionizing radiation may be responsible for the degradation of the physiologically important glycosaminoglycan hyaluronan [10,26,27].…”

“…Radiation response of articular cartilage is inconsistent in very young animal models, although a totalbody irradiation study indicates inducing of clinically relevant degenerative changes in the articular cartilage of immature rats [25]. But articular cartilage from adult humans or large animal species seems to degrade after exposure [24,29].…”

The effects of low-dose radiation on articular cartilage: a review

“…Willey et al found that irradiation lowered the synthesis of proteoglycans, induced active degradation of the matrix, as well as arthropathy and Lindburg et al found similar results in that low-dose radiation caused changes in the mechanical properties of articular cartilage, which may be due to the acute release of glycosaminoglycans [20]. Another similar study also found that when articular cartilage was exposed to 3 and 7Gy, degenerative changes to the tissue were observed [27].…”

Introduction to Michael E. Robbins Memorial Issue

“…At both Iowa and Wake Forest, Mike continued to build on his reputation as a researcher, instructor, and, importantly to him, as a teacher and mentor of junior faculty. His outstanding leadership, commitment to his trainees, and excellent teaching skills are exemplified by the normal tissue papers in this issue from those that have looked to, and benefited from, Mike for mentorship and support over the years (Greene-Schloesser et al 2014 , Hutchinson et al 2014 , Peiffer et al 2014 ).…”