Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity
Objective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-...
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Elsevier
2018-12-01
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Series: | Bone Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352187218300548 |
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author | Nancy E. Lane Geetha Mohan Wei Yao Kie Shidara Yu-An Evan Lay Jia Junjing Alanna Dubrovsky Donald B. Kimmel |
author_facet | Nancy E. Lane Geetha Mohan Wei Yao Kie Shidara Yu-An Evan Lay Jia Junjing Alanna Dubrovsky Donald B. Kimmel |
author_sort | Nancy E. Lane |
collection | DOAJ |
description | Objective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1–34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body. Results: The prevalence of ON was 14% in the Con group and 36% in the GC-only group (P = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1–34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups. Conclusion: Neither LLP2A-Ale nor hPTH (1–34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1–34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice. Keywords: hPTH (1–34), LLP2A-Ale, Distal femoral epiphysis, Dexamethasone, Prevention |
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issn | 2352-1872 |
language | English |
last_indexed | 2024-12-22T01:36:22Z |
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spelling | doaj.art-c3d564213e49490d8aaf0f7088f1a7772022-12-21T18:43:21ZengElsevierBone Reports2352-18722018-12-019181187Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularityNancy E. Lane0Geetha Mohan1Wei Yao2Kie Shidara3Yu-An Evan Lay4Jia Junjing5Alanna Dubrovsky6Donald B. Kimmel7Center for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA 95817, USA; Corresponding author at: Center for Musculoskeletal Health, U. C. Davis School of Medicine, 4625 Second Avenue, Suite 2006, Sacramento, CA 95918.Center for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA 95817, USACenter for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA 95817, USACenter for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA 95817, USACenter for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA 95817, USAFacility of Animal Science, Yunnan Agricultural University, Kunming, Yunnan, 650201, ChinaCenter for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA 95817, USADepartment of Physiological Sciences, University of Florida, Gainesville, FL 32610, USAObjective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1–34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body. Results: The prevalence of ON was 14% in the Con group and 36% in the GC-only group (P = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1–34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups. Conclusion: Neither LLP2A-Ale nor hPTH (1–34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1–34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice. Keywords: hPTH (1–34), LLP2A-Ale, Distal femoral epiphysis, Dexamethasone, Preventionhttp://www.sciencedirect.com/science/article/pii/S2352187218300548 |
spellingShingle | Nancy E. Lane Geetha Mohan Wei Yao Kie Shidara Yu-An Evan Lay Jia Junjing Alanna Dubrovsky Donald B. Kimmel Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity Bone Reports |
title | Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity |
title_full | Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity |
title_fullStr | Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity |
title_full_unstemmed | Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity |
title_short | Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity |
title_sort | prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity |
url | http://www.sciencedirect.com/science/article/pii/S2352187218300548 |
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