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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Main Authors: Nancy E. Lane, Geetha Mohan, Wei Yao, Kie Shidara, Yu-An Evan Lay, Jia Junjing, Alanna Dubrovsky, Donald B. Kimmel
Format: Article
Language:English
Published: Elsevier 2018-12-01
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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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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