Skeletal effects of short-term exposure to dexamethasone and response to risedronate treatment studied in vivo in rabbits by magnetic resonance micro-imaging and spectroscopy

Masaya Takahashi, Punam K. Saha, Felix W. Wehrli

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13 Citations (Scopus)

Abstract

Supraphysiological levels of glucocorticoids (GC) cause bone atrophy and growth retardation. In this study, we examine whether these adverse structural effects are reversible and whether treatment with bisphosphonate is protective by in vivo serial micro-magnetic resonance (μ-MR) imaging and spectroscopy. Rabbits (n = 16) were divided into four groups, a control group (n = 4) and three groups (n = 4 each) receiving GC in the form of dexamethasone (0.45 mg/kg/day). In one of the GC groups dexamethasone exposure was discontinued after 2 weeks, the other two groups were maintained on dexamethasone, with one receiving risedronate (5 μg/kg twice per week) from the beginning of treatment, the other one receiving risedronate after 2 weeks. Animals were imaged at baseline and at 2, 4, and 8 weeks. Trabecular bone volume fraction (trabecular bone volume/tissue volume, TB/TV), trabecular bone thickness (Tb.Th), and topological structural parameters were measured in the distal femoral epiphysis, as was the epiphyseal growth plate (EGP), and marrow fat fraction, which was computed from the integrated proton spectra. Two weeks of dexamethasone exposure substantially reduced TB/TV, along with thinning of the epiphyseal growth plate and conversion of hematopoietic to adipocytic marrow. However, TB/TV recovered to normal levels within 2 weeks after cessation of GC exposure and remained constant throughout the remainder of the protocol. In contrast, neither EGP thickness nor marrow composition returned to control levels after cessation of GC exposure as rapidly as did TB/TV. Besides increased TB/TV, bisphosphonate treatment resulted in a more connected platelike network than observable at baseline, but GP atrophy and marrow conversion caused by GC exposure were not affected. The data lend support to a protective effect of risedronate on trabecular architecture during GC exposure. The improvement in trabecular network parameters beyond baseline values further suggest a therapeutic effect of risedronate.

Original languageEnglish (US)
Pages (from-to)467-475
Number of pages9
JournalJournal of Bone and Mineral Metabolism
Volume24
Issue number6
DOIs
StatePublished - Nov 2006

Fingerprint

Growth Plate
Dexamethasone
Glucocorticoids
Magnetic Resonance Spectroscopy
Magnetic Resonance Imaging
Rabbits
Bone and Bones
Bone Marrow
Diphosphonates
Atrophy
Epiphyses
Bone Development
Therapeutic Uses
Thigh
Cancellous Bone
Risedronate Sodium
Protons
Fats
Control Groups

Keywords

  • Bisphosphonate
  • Corticosteroid-induced osteoporosis
  • Femoral epiphyseal trabecular bone
  • NMR microscopy
  • Rabbit

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "Skeletal effects of short-term exposure to dexamethasone and response to risedronate treatment studied in vivo in rabbits by magnetic resonance micro-imaging and spectroscopy",
abstract = "Supraphysiological levels of glucocorticoids (GC) cause bone atrophy and growth retardation. In this study, we examine whether these adverse structural effects are reversible and whether treatment with bisphosphonate is protective by in vivo serial micro-magnetic resonance (μ-MR) imaging and spectroscopy. Rabbits (n = 16) were divided into four groups, a control group (n = 4) and three groups (n = 4 each) receiving GC in the form of dexamethasone (0.45 mg/kg/day). In one of the GC groups dexamethasone exposure was discontinued after 2 weeks, the other two groups were maintained on dexamethasone, with one receiving risedronate (5 μg/kg twice per week) from the beginning of treatment, the other one receiving risedronate after 2 weeks. Animals were imaged at baseline and at 2, 4, and 8 weeks. Trabecular bone volume fraction (trabecular bone volume/tissue volume, TB/TV), trabecular bone thickness (Tb.Th), and topological structural parameters were measured in the distal femoral epiphysis, as was the epiphyseal growth plate (EGP), and marrow fat fraction, which was computed from the integrated proton spectra. Two weeks of dexamethasone exposure substantially reduced TB/TV, along with thinning of the epiphyseal growth plate and conversion of hematopoietic to adipocytic marrow. However, TB/TV recovered to normal levels within 2 weeks after cessation of GC exposure and remained constant throughout the remainder of the protocol. In contrast, neither EGP thickness nor marrow composition returned to control levels after cessation of GC exposure as rapidly as did TB/TV. Besides increased TB/TV, bisphosphonate treatment resulted in a more connected platelike network than observable at baseline, but GP atrophy and marrow conversion caused by GC exposure were not affected. The data lend support to a protective effect of risedronate on trabecular architecture during GC exposure. The improvement in trabecular network parameters beyond baseline values further suggest a therapeutic effect of risedronate.",
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author = "Masaya Takahashi and Saha, {Punam K.} and Wehrli, {Felix W.}",
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AU - Takahashi, Masaya

AU - Saha, Punam K.

AU - Wehrli, Felix W.

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N2 - Supraphysiological levels of glucocorticoids (GC) cause bone atrophy and growth retardation. In this study, we examine whether these adverse structural effects are reversible and whether treatment with bisphosphonate is protective by in vivo serial micro-magnetic resonance (μ-MR) imaging and spectroscopy. Rabbits (n = 16) were divided into four groups, a control group (n = 4) and three groups (n = 4 each) receiving GC in the form of dexamethasone (0.45 mg/kg/day). In one of the GC groups dexamethasone exposure was discontinued after 2 weeks, the other two groups were maintained on dexamethasone, with one receiving risedronate (5 μg/kg twice per week) from the beginning of treatment, the other one receiving risedronate after 2 weeks. Animals were imaged at baseline and at 2, 4, and 8 weeks. Trabecular bone volume fraction (trabecular bone volume/tissue volume, TB/TV), trabecular bone thickness (Tb.Th), and topological structural parameters were measured in the distal femoral epiphysis, as was the epiphyseal growth plate (EGP), and marrow fat fraction, which was computed from the integrated proton spectra. Two weeks of dexamethasone exposure substantially reduced TB/TV, along with thinning of the epiphyseal growth plate and conversion of hematopoietic to adipocytic marrow. However, TB/TV recovered to normal levels within 2 weeks after cessation of GC exposure and remained constant throughout the remainder of the protocol. In contrast, neither EGP thickness nor marrow composition returned to control levels after cessation of GC exposure as rapidly as did TB/TV. Besides increased TB/TV, bisphosphonate treatment resulted in a more connected platelike network than observable at baseline, but GP atrophy and marrow conversion caused by GC exposure were not affected. The data lend support to a protective effect of risedronate on trabecular architecture during GC exposure. The improvement in trabecular network parameters beyond baseline values further suggest a therapeutic effect of risedronate.

AB - Supraphysiological levels of glucocorticoids (GC) cause bone atrophy and growth retardation. In this study, we examine whether these adverse structural effects are reversible and whether treatment with bisphosphonate is protective by in vivo serial micro-magnetic resonance (μ-MR) imaging and spectroscopy. Rabbits (n = 16) were divided into four groups, a control group (n = 4) and three groups (n = 4 each) receiving GC in the form of dexamethasone (0.45 mg/kg/day). In one of the GC groups dexamethasone exposure was discontinued after 2 weeks, the other two groups were maintained on dexamethasone, with one receiving risedronate (5 μg/kg twice per week) from the beginning of treatment, the other one receiving risedronate after 2 weeks. Animals were imaged at baseline and at 2, 4, and 8 weeks. Trabecular bone volume fraction (trabecular bone volume/tissue volume, TB/TV), trabecular bone thickness (Tb.Th), and topological structural parameters were measured in the distal femoral epiphysis, as was the epiphyseal growth plate (EGP), and marrow fat fraction, which was computed from the integrated proton spectra. Two weeks of dexamethasone exposure substantially reduced TB/TV, along with thinning of the epiphyseal growth plate and conversion of hematopoietic to adipocytic marrow. However, TB/TV recovered to normal levels within 2 weeks after cessation of GC exposure and remained constant throughout the remainder of the protocol. In contrast, neither EGP thickness nor marrow composition returned to control levels after cessation of GC exposure as rapidly as did TB/TV. Besides increased TB/TV, bisphosphonate treatment resulted in a more connected platelike network than observable at baseline, but GP atrophy and marrow conversion caused by GC exposure were not affected. The data lend support to a protective effect of risedronate on trabecular architecture during GC exposure. The improvement in trabecular network parameters beyond baseline values further suggest a therapeutic effect of risedronate.

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