Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice

Glucocorticoid-induced osteoporosis (GIO) is the most common causes of secondary osteoporosis. Several laboratory animals have been employed to model GIO, and multiple routes of administration have been utilized. Prednisolone delivered by pellets implanted subcutaneously has been suggested as a less...

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Autores principales:	Mikkel Bo Brent, Annemarie Brüel, Jesper Skovhus Thomsen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Glucocorticoids Bone histomorphometry Bone strength Pellets Bone loss Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/06824af3ceea4e5ea1916ff49bbf885c
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spelling	oai:doaj.org-article:06824af3ceea4e5ea1916ff49bbf885c2021-11-14T04:35:45ZSparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice2666-396110.1016/j.endmts.2021.100114https://doaj.org/article/06824af3ceea4e5ea1916ff49bbf885c2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666396121000376https://doaj.org/toc/2666-3961Glucocorticoid-induced osteoporosis (GIO) is the most common causes of secondary osteoporosis. Several laboratory animals have been employed to model GIO, and multiple routes of administration have been utilized. Prednisolone delivered by pellets implanted subcutaneously has been suggested as a less invasive alternative to daily injections, but how the severity of GIO varies between doses and the efficacy of short-term administration are not entirely elucidated. We investigated the skeletal effects of short-term exposure to glucocorticoid (GC) excess from implantable slow-release prednisolone pellets using two different doses (2.8 and 5.4 mg/kg/d). Forty-eight female Swiss mice were randomly allocated to the following four groups: 1: Baseline, 2: Placebo pellet (PP), 3: GC 5 mg, and 4: GC 10 mg. The study lasted four weeks. The musculoskeletal effects of GC were assessed by DXA, µCT, mechanical testing, dynamic bone histomorphometry, and histological quantification of bone and muscle cells. Both doses of GC significantly reduced bone mineral density, cortical mineralizing surfaces and mineral apposition rate, trabecular osteoid-covered surfaces, and rectus femoris muscle cell cross-sectional area compared with PP. In addition, the high dose of GC significantly reduced mid-diaphyseal bone strength compared with PP. Either dose had only minor impact on trabecular microstructure, while no negative effect was found on mid-diaphyseal cortical thickness. In conclusion, prednisolone pellet-induced short-term GC excess resulted in osteopenia, reduced bone formation indices, and only few dose-dependent differences were found.Mikkel Bo BrentAnnemarie BrüelJesper Skovhus ThomsenElsevierarticleGlucocorticoidsBone histomorphometryBone strengthPelletsBone lossDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENEndocrine and Metabolic Science, Vol 5, Iss , Pp 100114- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glucocorticoids Bone histomorphometry Bone strength Pellets Bone loss Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Glucocorticoids Bone histomorphometry Bone strength Pellets Bone loss Diseases of the endocrine glands. Clinical endocrinology RC648-665 Mikkel Bo Brent Annemarie Brüel Jesper Skovhus Thomsen Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice
description	Glucocorticoid-induced osteoporosis (GIO) is the most common causes of secondary osteoporosis. Several laboratory animals have been employed to model GIO, and multiple routes of administration have been utilized. Prednisolone delivered by pellets implanted subcutaneously has been suggested as a less invasive alternative to daily injections, but how the severity of GIO varies between doses and the efficacy of short-term administration are not entirely elucidated. We investigated the skeletal effects of short-term exposure to glucocorticoid (GC) excess from implantable slow-release prednisolone pellets using two different doses (2.8 and 5.4 mg/kg/d). Forty-eight female Swiss mice were randomly allocated to the following four groups: 1: Baseline, 2: Placebo pellet (PP), 3: GC 5 mg, and 4: GC 10 mg. The study lasted four weeks. The musculoskeletal effects of GC were assessed by DXA, µCT, mechanical testing, dynamic bone histomorphometry, and histological quantification of bone and muscle cells. Both doses of GC significantly reduced bone mineral density, cortical mineralizing surfaces and mineral apposition rate, trabecular osteoid-covered surfaces, and rectus femoris muscle cell cross-sectional area compared with PP. In addition, the high dose of GC significantly reduced mid-diaphyseal bone strength compared with PP. Either dose had only minor impact on trabecular microstructure, while no negative effect was found on mid-diaphyseal cortical thickness. In conclusion, prednisolone pellet-induced short-term GC excess resulted in osteopenia, reduced bone formation indices, and only few dose-dependent differences were found.
format	article
author	Mikkel Bo Brent Annemarie Brüel Jesper Skovhus Thomsen
author_facet	Mikkel Bo Brent Annemarie Brüel Jesper Skovhus Thomsen
author_sort	Mikkel Bo Brent
title	Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice
title_short	Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice
title_full	Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice
title_fullStr	Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice
title_full_unstemmed	Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice
title_sort	sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred swiss mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/06824af3ceea4e5ea1916ff49bbf885c
work_keys_str_mv	AT mikkelbobrent sparsedosedependentdifferenceinskeletaleffectsofshorttermglucocorticoidexcessinoutbredswissmice AT annemariebruel sparsedosedependentdifferenceinskeletaleffectsofshorttermglucocorticoidexcessinoutbredswissmice AT jesperskovhusthomsen sparsedosedependentdifferenceinskeletaleffectsofshorttermglucocorticoidexcessinoutbredswissmice
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Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice

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