Leg Length Discrepancy Following Irradiation for Childhood Tumors

Ww, Robertson; Ms, Butler; Gj, D'Angio; Wr, Rate

doi:10.1097/01241398-199105000-00002

Cited by 35 publications

(11 citation statements)

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“…The longitudinal growth of bone is known to be a result of the orderly coordination of chondrocyte proliferation and hypertrophy, calcification of the matrix, vascular invasion, and completion of endochondral bone formation in the growth plate [Butler et al, 1990;Goldwein, 1991;Robertson et al, 1991]. Radiotherapy for bone or soft-tissue sarcomas close to the growth plate can result in the development of growth arrest, angular deformity, and/or limb length discrepancy.…”

Section: Introductionmentioning

confidence: 99%

Microarray Analysis of Irradiated Growth Plate Zones following Laser Microdissection Shows Later Importance of Differentially Expressed Genes during Radiorecovery

Pritchard

Horton²,

Keenawinna³

et al. 2010

Cells Tissues Organs

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Purpose: Potential targets for selective radiorecovery modulation were investigated via the identification of late upregulated genes and pathways during growth plate chondrocyte recovery. Methods and Materials: Three groups of six 5-week-old male Sprague-Dawley rats underwent fractionated irradiation to the right tibiae over 5 days totaling 17.5 Gy and were then killed at 7, 11, and 16 days following the first radiotherapy fraction. The growth plates were collected from the proximal tibiae bilaterally and subsequently underwent laser microdissection to separate reserve, perichondral, proliferative, and hypertrophic zones. Differential gene expression was analyzed between irradiated right and nonirradiated left tibiae using RAE230 2.0 GeneChip microarray, compared between zones and time points, and subjected to functional pathway cluster analysis with real-time polymerase chain reaction (PCR) to confirm selected results. Results: The reserve zone showed the greatest number of differentially expressed genes and enriched pathways: 259 and 134, respectively. Differentially expressed genes included: Timp3, Gpx1, Gas6, Notch2, VEGF, and HIF-1. Enriched pathways included the developmental processes of regeneration, antiapoptosis, developmental growth, tissue regeneration, mesenchymal cell proliferation, negative regulation of immune response, and determination of symmetry. The reserve zone late upregulation of genes was validated using real-time PCR for Mgp, Gas6, and Eef1a1. Conclusions: A significant difference in late upregulated genes between growth plate zones exists. The reserve zone shows the greatest change, containing a 10-fold increase in the total number of genes differentially expressed between days 7 and 16. These findings suggest that reserve zone chondrocytes may play a later role in growth plate recovery response following irradiation.

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Section: Introductionmentioning

confidence: 99%

Microarray Analysis of Irradiated Growth Plate Zones following Laser Microdissection Shows Later Importance of Differentially Expressed Genes during Radiorecovery

Pritchard

Horton²,

Keenawinna³

et al. 2010

Cells Tissues Organs

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“…The animals were weighed and then placed on an acrylic sheet with the right leg extended, secured with tape, and placed under the radiation source (Philips MGC 30; Shelton, CT). Radiation was administered using 300 kV X rays at 10 mA with a 30-cm source-to-skin distance and a dose rate of 2.56 Gy/min (3). The exposure time for each 3.5-Gy fraction was 1.37 min.…”

Section: Methodsmentioning

confidence: 99%

“…Radiotherapy is used as an adjunct to surgical excision for soft tissue sarcomas such as synovial sarcoma and may be used as an alternative to surgery for rhabdomyosarcoma and Ewing’s sarcoma. However, in patients with immature skeletons, radiotherapy frequently results in asymmetric limb growth arrest and resultant limb length discrepancy due to physeal damage from local radiation effects when the physis is included in the radiation field (1–3). …”

Section: Introductionmentioning

confidence: 99%

Histomorphometric Evidence of Growth Plate Recovery Potential after Fractionated Radiotherapy: AnIn VivoModel

et al. 2008

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This study evaluated the hypothesis that early growth plate radiorecovery is evident by growth rate, histomorphometric and immunohistochemical end points after exposure to clinically relevant fractionated radiation in vivo. Twenty-four weanling 5-week-old male Sprague-Dawley rats were randomized into eight groups. In each animal, the right distal femur and proximal tibia were exposed to five daily fractions of 3.5 Gy (17.5 Gy) with the left leg serving as a control. Rats were killed humanely at 7, 8, 9, 10, 11, 14, 15 and 16 days after the first day of radiation exposure. Quantitative end points calculated included individual zonal and overall growth plate heights, area matrix fraction, OTC-labeled growth rate, chondrocyte clone volume and numeric density, and BrdU immunohistochemical labeling for proliferative index. Transient postirradiation reductions occurred early and improved during observation for growth rate, proliferative indices, transitional/ hypertrophic zone matrix area fraction, proliferative height, and clonal volume. Reserve and hypertrophic zone height remained increased during the period of observation. The current model, using a more clinically relevant fractionation scheme than used previously, shows early evidence of growth plate recovery and provides a model that can be used to correlate temporal changes in RNA and protein expression during the early period of growth plate recovery.

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“…Radiotherapy plays an important role as part of the multimodality treatment for a number of malignancies in children. In young children, significant growth arrest was demonstrated with fractionated doses of 15 Gy and above as well as, in children less than one year of age, with doses as low as 10 Gy (Robertson et al 1991). Proliferating chondrocytes, distal metaphyseal vessels, and epiphyseal vasculature are main targets for radiation-induced injury of bone growth plate (Kember 1967).…”

Section: Radioprotective Effect Of Melatonin and Its Metabolitesmentioning

confidence: 99%