Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection.
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Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection. / Beil, Frank Timo; Oheim, Ralf; Barvencik, Florian; Hissnauer, Tim N; Pestka, Jan-Malte; Ignatius, Anita; Rueger, Johannes M; Schinke, Thorsten; Clarke, Iain J; Amling, Michael; Pogoda, Pia.
in: J ORTHOP RES, Jahrgang 30, Nr. 8, 8, 2012, S. 1254-1262.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection.
AU - Beil, Frank Timo
AU - Oheim, Ralf
AU - Barvencik, Florian
AU - Hissnauer, Tim N
AU - Pestka, Jan-Malte
AU - Ignatius, Anita
AU - Rueger, Johannes M
AU - Schinke, Thorsten
AU - Clarke, Iain J
AU - Amling, Michael
AU - Pogoda, Pia
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Female
KW - Disease Models, Animal
KW - Bone Remodeling/physiology
KW - Hypothalamus/physiology/surgery
KW - Osteoblasts/metabolism
KW - Osteoclasts/metabolism
KW - Osteoporosis/etiology/radiography
KW - Pituitary Gland/physiology
KW - Sheep, Domestic
KW - Animals
KW - Female
KW - Disease Models, Animal
KW - Bone Remodeling/physiology
KW - Hypothalamus/physiology/surgery
KW - Osteoblasts/metabolism
KW - Osteoclasts/metabolism
KW - Osteoporosis/etiology/radiography
KW - Pituitary Gland/physiology
KW - Sheep, Domestic
M3 - SCORING: Journal article
VL - 30
SP - 1254
EP - 1262
JO - J ORTHOP RES
JF - J ORTHOP RES
SN - 0736-0266
IS - 8
M1 - 8
ER -
