title: Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection.
abstract: The hypothalamus is of critical importance in regulating bone remodeling. This is underscored by the fact that intracerebroventricular-application of leptin in ewe leads to osteopenia. As a large animal model of osteoporosis, this approach has some limitations, such as high technical expenditure and running costs. Therefore we asked if a surgical ablation of the leptin signaling axis would have the same effects and would thereby be a more useful model. We analyzed the bone phenotype of ewe after surgical hypothalamo-pituitary disconnection (HPD + OVX) as compared to control ewe (OVX) after 3 and 12 months. Analyses included histomorphometric characterization, micro-CT and measurement of bone turnover parameters. Already 3 months after HPD we found osteopenic ewe with a significantly decreased bone formation (69%) and osteoclast activity (49%). After a period of 12 months the HPD group additionally developed an (preclinical) osteoporosis with significant reduction (33%) of femoral cortical thickness, as compared to controls (OVX). Taken together, HPD leads after 12 month to osteoporosis with a reduction in both trabecular and cortical bone caused by a low bone turnover situation, with reduced osteoblast and osteoclast activity, as compared to controls (OVX). The HPD-sheep is a suitable large animal model of osteoporosis. Furthermore our results indicate that an intact hypothalamo-pituitary axis is required for activation of bone turnover.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Frank Timo
authors.initials: FT
authors.lastname: Beil
authors.forename: Ralf
authors.initials: R
authors.lastname: Oheim
authors.forename: Florian
authors.initials: F
authors.lastname: Barvencik
authors.forename: Tim N
authors.initials: TN
authors.lastname: Hissnauer
authors.forename: Jan M
authors.initials: JM
authors.lastname: Pestka
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Rueger
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Clarke
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Pia
authors.initials: P
authors.lastname: Pogoda
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D007031:Hypothalamus / Q000502:physiology* / Q000601:surgery; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000209:etiology*; D010902:Pituitary Gland / Q000502:physiology*; D011859:Radiography; D034561:Sheep, Domestic