Relative effects of radiation-induced changes in bone mass, structure, and tissue material on vertebral strength in a rat model

Emerzian, Shannon R.<sup>1</sup>; Wu, Tongge<sup>1</sup>; Vaidya, Rachana<sup>2</sup>; Tang, Simon Y.<sup>2,3,4</sup>; Abergel, Rebecca J.<sup>5</sup>; Keaveny, Tony M.<sup>1,6</sup>

Affiliations

¹Department of Mechanical Engineering, University of California, Berkeley, CA, USA

²Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA

³Department of Biomedical Engineering, Washington University, St. Louis, MO, USA

⁴Department of Material Science & Mechanical Engineering, Washington University, St. Louis, MO, USA

⁵Department of Nuclear Engineering, University of California, Berkeley, CA, USA

⁶Department of Bioengineering, University of California, Berkeley, CA, USA

Abstract and keywords

The observed increased risk of fracture after cancer radiation therapy is presumably due to a radiation-induced reduction in whole-bone strength. However, the mechanisms for impaired strength remain unclear, as the increased fracture risk is not fully explained by changes in bone mass. To provide insight, a small animal model was used to determine how much of this whole-bone weakening effect for the spine is attributable to changes in bone mass, structure, and material properties of the bone tissue and their relative effects. Further, because women have a greater risk of fracture after radiation therapy than men, we investigated if sex had a significant influence on bone's response to irradiation. Fractionated in vivo irradiation (10 × 3 Gy) or sham irradiation (0 Gy) was administered daily to the lumbar spine in twenty-seven 17-week-old Sprague–Dawley rats (n = 6–7/sex/group). Twelve weeks after final treatment, animals were euthanized, and lumbar vertebrae (L₄ and L₅) were isolated. Using a combination of biomechanical testing, micro-CT-based finite element analysis, and statistical regression analysis, we separated out the effect of mass, structural, and tissue material changes on vertebral strength. Compared with the sham group (mean ± SD strength = 420 ± 88 N), the mean strength of the irradiated group was lower by 28% (117 N/420 N, p < 0.0001). Overall, the response of treatment did not differ with sex. By combining results from both general linear regression and finite element analyses, we calculated that mean changes in bone mass, structure, and material properties of the bone tissue accounted for 56% (66 N/117 N), 20% (23 N/117 N), and 24% (28 N/117 N), respectively, of the overall change in strength. As such, these results provide insight into why an elevated clinical fracture risk for patients undergoing radiation therapy is not well explained by changes in bone mass alone.

Keywords: BIOMECHANICS; RADIATION THERAPY; IONIZING RADIATION; FINITE ELEMENT ANALYSIS

Links

DOI: 10.1002/jbmr.4828

PubMed: 37191221

WoS: 001000652100001

History

Received: 2022-12-01

Revised: 2023-04-06

Accepted: 2023-05-07

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