title: Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.
abstract: Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Oheim
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany; Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Maciej J K
authors.initials: MJK
authors.lastname: Simon
authors.affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Helmholtzstr. 14, 89081 Ulm, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Steiner
authors.affiliation: Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Eik
authors.initials: E
authors.lastname: Vettorazzi
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Barvencik
authors.affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Helmholtzstr. 14, 89081 Ulm, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: amling@uke.uni-hamburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.affiliation: Department of Physiology, Neuroendocrine Research Group, Monash University, Clayton Campus, Melbourne, Victoria 3800, Australia.
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Clarke
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Pogoda
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: F Timo
authors.initials: FT
authors.lastname: Beil
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001862:Bone Resorption / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D004195:Disease Models, Animal; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020249:Hormone Replacement Therapy; D010024:Osteoporosis / Q000473:pathology*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000473:pathology*; D012756:Sheep; D013974:Thyroxine / Q000494:pharmacology*
chemical_list: D004967:Estrogens; D013974:Thyroxine
keywords: Estrogen and thyroxin; Hypothalamic-pituitary disconnection (HPD); Large animal model; Low-turnover; Osteoporosis; Sheep