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 (micro-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 microg/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.
authors.affiliation: Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Punam K
authors.initials: PK
authors.lastname: Saha
authors.forename: Felix W
authors.initials: FW
authors.lastname: Wehrli
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D003907:Dexamethasone / Q000494:pharmacology*; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011817:Rabbits; D011877:Radionuclide Imaging; D000068296:Risedronic Acid; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000068296:Risedronic Acid; D012968:Etidronic Acid