Trần Phong
Senior Member
Em đang làm về mô hình chuột bị tổn thương xương, bằng glucocorticoid, em tìm được bài báo này nhưng không tải được mong anh chị và các bạn giúp em. Em cám ơn rất nhiều !!
http://www3.interscience.wiley.com/journal/121372022/abstract?CRETRY=1&SRETRY=0
A mouse model for glucocorticoid-induced osteonecrosis: Effect of a steroid holiday
Lei Yang 1 2, Kelli Boyd 3, Sue C. Kaste 5 6, Landry Kamdem Kamdem 1, Richard J. Rahija 4, Mary V. Relling 1 2 *
1Departement of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
2Departement of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38105
3Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, Tennessee
4Animal Resource Center, St. Jude Children's Research Hospital, Memphis, Tennessee
5Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
6Departement of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
email: Mary V. Relling (mary.relling@stjude.org)
*Correspondence to Mary V. Relling, Departement of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee. T: 901-495-2348; F: 901-525-6869.
Keywords
glucocorticoid • osteonecrosis • mouse model
Abstract
Glucocorticoid-induced osteonecrosis is a common and dose-limiting adverse event. The goal of this study was to establish a mouse model of glucocorticoid-induced osteonecrosis suitable for testing the effects of different treatment strategies on its frequency. Fourteen murine strains were screened using various glucocorticoids, routes of administration, and diets. Four-week-old male BALB/cJ mice were treated with oral dexamethasone for up to 12 weeks either by continuous dosing or by discontinuous dosing, with or without asparaginase. Histopathological features of the distal femurs were examined by light microscopy. Osteonecrotic lesions were characterized by empty lacunae and osteocyte ghosts in trabecular bone surrounded by necrotic marrow and edema. The incidence of dexamethasone induced osteonecrosis in BALB/cJ mice was 40-45% (4/10 or 5/11) at 12 weeks. The frequency of osteonecrosis trended lower after discontinuous compared to continuous dosing for 12 weeks (8 vs. 45%) (p = 0.06) despite comparable cumulative plasma exposure. Asparaginase hastened the occurrence of osteonecrosis, which was observed as early as 4 weeks and the incidence was 50% after 6 weeks. A mouse model of glucocorticoid-induced osteonecrosis was established. Discontinuous was less osteonecrotic than continuous dexamethasone treatment, consistent with the possible benefits of a steroid holiday seen in clinical settings. Moreover, asparaginase hastened osteonecrosis, indicating that drugs may interact with glucocorticoids to affect osteonecrosis risk. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
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Received: 5 February 2008; Accepted: 5 June 2008
http://www3.interscience.wiley.com/journal/121372022/abstract?CRETRY=1&SRETRY=0
A mouse model for glucocorticoid-induced osteonecrosis: Effect of a steroid holiday
Lei Yang 1 2, Kelli Boyd 3, Sue C. Kaste 5 6, Landry Kamdem Kamdem 1, Richard J. Rahija 4, Mary V. Relling 1 2 *
1Departement of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
2Departement of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38105
3Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, Tennessee
4Animal Resource Center, St. Jude Children's Research Hospital, Memphis, Tennessee
5Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
6Departement of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
email: Mary V. Relling (mary.relling@stjude.org)
*Correspondence to Mary V. Relling, Departement of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee. T: 901-495-2348; F: 901-525-6869.
Keywords
glucocorticoid • osteonecrosis • mouse model
Abstract
Glucocorticoid-induced osteonecrosis is a common and dose-limiting adverse event. The goal of this study was to establish a mouse model of glucocorticoid-induced osteonecrosis suitable for testing the effects of different treatment strategies on its frequency. Fourteen murine strains were screened using various glucocorticoids, routes of administration, and diets. Four-week-old male BALB/cJ mice were treated with oral dexamethasone for up to 12 weeks either by continuous dosing or by discontinuous dosing, with or without asparaginase. Histopathological features of the distal femurs were examined by light microscopy. Osteonecrotic lesions were characterized by empty lacunae and osteocyte ghosts in trabecular bone surrounded by necrotic marrow and edema. The incidence of dexamethasone induced osteonecrosis in BALB/cJ mice was 40-45% (4/10 or 5/11) at 12 weeks. The frequency of osteonecrosis trended lower after discontinuous compared to continuous dosing for 12 weeks (8 vs. 45%) (p = 0.06) despite comparable cumulative plasma exposure. Asparaginase hastened the occurrence of osteonecrosis, which was observed as early as 4 weeks and the incidence was 50% after 6 weeks. A mouse model of glucocorticoid-induced osteonecrosis was established. Discontinuous was less osteonecrotic than continuous dexamethasone treatment, consistent with the possible benefits of a steroid holiday seen in clinical settings. Moreover, asparaginase hastened osteonecrosis, indicating that drugs may interact with glucocorticoids to affect osteonecrosis risk. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
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Received: 5 February 2008; Accepted: 5 June 2008
