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.

Keywords::

• Radiation
• articular cartilage
• knee joints
• arthritis
• 7T MRI
• nanocomputed tomography

Acknowledgements

We would like to gratefully acknowledge Dr Michael Robbins for his mentoring, training, and enthusiasm for pursuing research in the field of late radiation-induced skeletal injury. Dr Ted Bateman graciously provided access to the microCT. We thank Dr Raghunatha Yammani for scoring all the histologic slides for cartilage damage.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported in part by a National Space Biomedical Research Institute Career Advancement Award EO00008 through NASA NCC 9-58 [JSW], R01-CA136910-S1 [MTM], R01-CA112593-S1 to Michael E Robbins, the Physician Scientist Training Program in Orthopaedic Surgery [L.A. Koman, MD], the National Science Foundation Award #0959511 [BC], and T32 CA113267 [JSW].