Author

Samantha Hay

Document Type

Honors Capstone Project

Date of Submission

Spring 5-1-2012

Capstone Advisor

Professor Joseph Spadaro, Ph.D.

Honors Reader

Professor Cristina Marchetti, Ph.D.

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Capstone Prize Winner

no

Won Capstone Funding

no

Honors Categories

Sciences and Engineering

Subject Categories

Biochemistry, Biophysics, and Structural Biology | Other Biochemistry, Biophysics, and Structural Biology

Abstract

Radiotherapy is an important part of cancer therapy, used in addition to surgery for treatment of patients with soft tissue sarcomas, and alternatively for treatment of patients with Ewing sarcoma of bone. Treating pediatric extremity tumors with radiotherapy has been shown to have harmful effects on the epiphyseal plate, resulting in permanent limb shortening and deformity when bone growth centers are exposed to radiation. Mechanical signals, specifically low-magnitude high-frequency vibrations (LMHFV), have been shown to be non-invasive and non-pharmacological growth factors in bone that have the potential to serve as a safe treatment for a number of clinical conditions. Thus, this study was aimed at evaluating the possible beneficial effects of low-magnitude high-frequency mechanical vibration (LMHFV) stimuli on growing irradiated bone and the possibility for restoration of function of the epiphyseal plate, a research topic that has never before been published in the literature.

Eighteen 3-week old weanling male Sprague-Dawley rats were subjected to a standard radiation dose of 17.5 Gray applied to right hind limbs, with the contralateral leg serving as a non-irradiated control. Then, the animals were divided into three groups: A) rats subjected to (LMHFV) only at 45 Hz, 0.3 g for 20 minutes once per day, 7 days/week, for 3 weeks, B) rats subjected the same conditions of LMHFV plus an injection of spermine NONOate, a nitric oxide donor that that has shown weak positive results as post-irradiation recovery agent, and C) rats subjected to sham LMHFV. After euthanizing the animals, skeletal growth was measured by x-ray analysis, marrow mesenchymal stem cell osteoblastic potential was measured by CFU-F analysis, and bone morphology was measured by micro-CT analysis.

X-ray and CFU-F analyses show statistically significant differences between right and left limbs in all groups. No statistical significance was observed between vibration versus control groups, but trends suggest there could be some positive effect of vibration, although not statistically significant. Micro-CT results show a clear difference between right and left limbs in all groups. Regarding vibration versus control groups, micro-CT results are ambiguous, but do suggest that vibration may have altered local growth characteristics and stimulated local shape changes in the 20% region from the distal end of the femur, just above the growth plate.

Despite the number of positive reports of LMHFV on bone, the present study did not reveal a clear, statistically significant effect on growth, structure or MSC colony formation. Thus, the effects of vibrational loading on irradiated growing bone are still unclear. Findings in this paper suggest that LMHFV may have a subtle positive effect, but this cannot be said with any statistical certainty. More studies on the effects of LMHFV on irradiated growing bone are needed to delineate the findings of this paper.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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