Quantifying intra-osseous growth of osteosarcoma in a murine model with radiographic analysis

Authors

  • Heather A. Cole,

    1. Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, 1211 Medical Center Dr., Nashville, TN 37232
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  • Jiro Ichikawa,

    1. Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, 1211 Medical Center Dr., Nashville, TN 37232
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  • Daniel C. Colvin,

    1. Department of Radiology and Radiological Sciences, Vanderbilt University, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232
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  • Lynda O'Rear,

    1. Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, 1211 Medical Center Dr., Nashville, TN 37232
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  • Jonathan G. Schoenecker

    Corresponding author
    1. Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, 1211 Medical Center Dr., Nashville, TN 37232
    2. Department of Radiology and Radiological Sciences, Vanderbilt University, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232
    3. Department of Pharmacology, Vanderbilt University, 1211 Medical Center Dr., Nashville, TN 37232
    4. Department of Pediatrics, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN 37232
    • Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, 1211 Medical Center Dr., Nashville, TN 37232. T: (615)-936-3080; F: (6l5)-322-3260
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Abstract

The orthotopic murine osteosarcoma model is an excellent representation of the human condition as mice develop rapid growth of ‘primary’ tumor with subsequent lung metastasis. Currently, monitoring tumor growth relies on measuring pulmonary metastases occurring four weeks post injection. Studies show that amputation of the tumor-bearing limb is required before pulmonary metastases are detectable due to rapid growth causing morbidity. Thus, a method measuring ‘primary’ tumor growth independent of metastasis is required. We hypothesized that serial radiography would allow for longitudinal quantification of ‘primary’ osteosarcoma growth and explored this idea by utilizing the tibial orthotopic model. Tumor growth was monitored weekly by radiography and calipers, and results were compared with µCT and histology. We found that radiographs demonstrate extra and intra-osseous tumor growth by displaying lytic and blastic lesions and the surrounding radio-opaque area enlarged significantly (p < 0.0001) allowing for quantification. Additionally, radiographs proved more precise than indirect caliper measurements (intra-observer error ±6.64%: inter-observer error ±15.84%). Therefore, we determined that radiography provides accurate, longitudinal quantification of ‘primary’ osteosarcoma tumor that can be performed serially in the same mouse, does not require introduction of bioluminescence to the host or cell, and is more precise than the current caliper method. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1957–1962, 2011

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