Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice

Abstract Glucocorticoids (GCs), such as prednisolone, are widely used to treat inflammatory diseases. Continuously long-term or high dose treatment with GCs is one of the most common causes of secondary osteoporosis and is associated with sarcopenia and increased risk of debilitating osteoporotic fr...

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Autores principales:	Mikkel Bo Brent, Jesper Skovhus Thomsen, Annemarie Brüel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe83de89c45641bd870184408434e0c7
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spelling	oai:doaj.org-article:fe83de89c45641bd870184408434e0c72021-12-02T17:52:23ZShort-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice10.1038/s41598-021-91729-82045-2322https://doaj.org/article/fe83de89c45641bd870184408434e0c72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91729-8https://doaj.org/toc/2045-2322Abstract Glucocorticoids (GCs), such as prednisolone, are widely used to treat inflammatory diseases. Continuously long-term or high dose treatment with GCs is one of the most common causes of secondary osteoporosis and is associated with sarcopenia and increased risk of debilitating osteoporotic fragility fractures. Abaloparatide (ABL) is a potent parathyroid hormone-related peptide analog, which can increase bone mineral density (aBMD), improve trabecular microarchitecture, and increase bone strength. The present study aimed to investigate whether GC excess blunts the osteoanabolic effect of ABL. Sixty 12–13-week-old female RjOrl:SWISS mice were allocated to the following groups: Baseline, Control, ABL, GC, and GC + ABL. ABL was administered as subcutaneous injections (100 μg/kg), while GC was delivered by subcutaneous implantation of a 60-days slow-release prednisolone-pellet (10 mg). The study lasted four weeks. GC induced a substantial reduction in muscle mass, trabecular mineral apposition rate (MAR) and bone formation rate (BFR/BS), and endocortical MAR compared with Control, but did not alter the trabecular microarchitecture or bone strength. In mice not receiving GC, ABL increased aBMD, bone mineral content (BMC), cortical and trabecular microarchitecture, mineralizing surface (MS/BS), MAR, BFR/BS, and bone strength compared with Control. However, when administered concomitantly with GC, the osteoanabolic effect of ABL on BMC, cortical morphology, and cortical bone strength was blunted. In conclusion, at cortical bone sites, the osteoanabolic effect of ABL is generally blunted by short-term GC excess.Mikkel Bo BrentJesper Skovhus ThomsenAnnemarie BrüelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mikkel Bo Brent Jesper Skovhus Thomsen Annemarie Brüel Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
description	Abstract Glucocorticoids (GCs), such as prednisolone, are widely used to treat inflammatory diseases. Continuously long-term or high dose treatment with GCs is one of the most common causes of secondary osteoporosis and is associated with sarcopenia and increased risk of debilitating osteoporotic fragility fractures. Abaloparatide (ABL) is a potent parathyroid hormone-related peptide analog, which can increase bone mineral density (aBMD), improve trabecular microarchitecture, and increase bone strength. The present study aimed to investigate whether GC excess blunts the osteoanabolic effect of ABL. Sixty 12–13-week-old female RjOrl:SWISS mice were allocated to the following groups: Baseline, Control, ABL, GC, and GC + ABL. ABL was administered as subcutaneous injections (100 μg/kg), while GC was delivered by subcutaneous implantation of a 60-days slow-release prednisolone-pellet (10 mg). The study lasted four weeks. GC induced a substantial reduction in muscle mass, trabecular mineral apposition rate (MAR) and bone formation rate (BFR/BS), and endocortical MAR compared with Control, but did not alter the trabecular microarchitecture or bone strength. In mice not receiving GC, ABL increased aBMD, bone mineral content (BMC), cortical and trabecular microarchitecture, mineralizing surface (MS/BS), MAR, BFR/BS, and bone strength compared with Control. However, when administered concomitantly with GC, the osteoanabolic effect of ABL on BMC, cortical morphology, and cortical bone strength was blunted. In conclusion, at cortical bone sites, the osteoanabolic effect of ABL is generally blunted by short-term GC excess.
format	article
author	Mikkel Bo Brent Jesper Skovhus Thomsen Annemarie Brüel
author_facet	Mikkel Bo Brent Jesper Skovhus Thomsen Annemarie Brüel
author_sort	Mikkel Bo Brent
title	Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
title_short	Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
title_full	Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
title_fullStr	Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
title_full_unstemmed	Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
title_sort	short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fe83de89c45641bd870184408434e0c7
work_keys_str_mv	AT mikkelbobrent shorttermglucocorticoidexcessbluntsabaloparatideinducedincreaseinfemoralbonemassandstrengthinmice AT jesperskovhusthomsen shorttermglucocorticoidexcessbluntsabaloparatideinducedincreaseinfemoralbonemassandstrengthinmice AT annemariebruel shorttermglucocorticoidexcessbluntsabaloparatideinducedincreaseinfemoralbonemassandstrengthinmice
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Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice

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