Sheep model for osteoporosis: sustainability and biomechanical relevance of low turnover osteoporosis induced by hypothalamic-pituitary disconnection.
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Sheep model for osteoporosis: sustainability and biomechanical relevance of low turnover osteoporosis induced by hypothalamic-pituitary disconnection. / Oheim, Ralf; Beil, Frank Timo; Köhne, Till; Wehner, Tim; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia.
In: J ORTHOP RES, Vol. 31, No. 7, 7, 2013, p. 1067-1074.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Sheep model for osteoporosis: sustainability and biomechanical relevance of low turnover osteoporosis induced by hypothalamic-pituitary disconnection.
AU - Oheim, Ralf
AU - Beil, Frank Timo
AU - Köhne, Till
AU - Wehner, Tim
AU - Barvencik, Florian
AU - Ignatius, Anita
AU - Amling, Michael
AU - Clarke, Iain J
AU - Pogoda, Pia
N1 - Copyright © 2013 Orthopaedic Research Society.
PY - 2013
Y1 - 2013
N2 - Hypothalamo-pituitary disconnection (HPD) leads to low bone turnover and osteoporosis in sheep. To determine the sustainability of bone loss and its biomechanical relevance, we studied HPD-sheep 24 months after surgery (HPD + OVX-24) in comparison to untreated control (Control), ovariectomized sheep (OVX), and sheep 12 months after HPD (HPD + OVX-12). We performed histomorphometric, HR-pQCT, and qBEI analyses, as well as biomechanical testing of all ewes studied. Twenty-four months after HPD, histomorphometric analyses of the iliac crest showed a significant reduction of BV/TV by 60% in comparison to Control. Cortical thickness of the femora measured by HR-pQCT did not change between 12 and 24 months after HPD but remained decreased by 30%. These structural changes were caused by a persisting depression of osteoblast and osteoclast cellular activity. Biomechanical testing of the femora showed a significant reduction of bending strength, whereas calcium content and distribution was found to be unchanged. In conclusion, HPD surgery leads to a persisting low turnover status with negative turnover balance in sheep followed by dramatic cortical and trabecular bone loss with consequent biomechanical impairment.
AB - Hypothalamo-pituitary disconnection (HPD) leads to low bone turnover and osteoporosis in sheep. To determine the sustainability of bone loss and its biomechanical relevance, we studied HPD-sheep 24 months after surgery (HPD + OVX-24) in comparison to untreated control (Control), ovariectomized sheep (OVX), and sheep 12 months after HPD (HPD + OVX-12). We performed histomorphometric, HR-pQCT, and qBEI analyses, as well as biomechanical testing of all ewes studied. Twenty-four months after HPD, histomorphometric analyses of the iliac crest showed a significant reduction of BV/TV by 60% in comparison to Control. Cortical thickness of the femora measured by HR-pQCT did not change between 12 and 24 months after HPD but remained decreased by 30%. These structural changes were caused by a persisting depression of osteoblast and osteoclast cellular activity. Biomechanical testing of the femora showed a significant reduction of bending strength, whereas calcium content and distribution was found to be unchanged. In conclusion, HPD surgery leads to a persisting low turnover status with negative turnover balance in sheep followed by dramatic cortical and trabecular bone loss with consequent biomechanical impairment.
KW - Animals
KW - Female
KW - Disease Models, Animal
KW - Ovariectomy
KW - Sheep
KW - Biomechanics/physiology
KW - Osteogenesis/physiology
KW - Osteoblasts/metabolism/pathology
KW - Bone and Bones/metabolism/pathology
KW - Bone Resorption/physiopathology
KW - Hypothalamus/physiology/surgery
KW - Osteoclasts/metabolism/pathology
KW - Osteoporosis/metabolism
KW - Pituitary Gland/physiology/surgery
KW - Animals
KW - Female
KW - Disease Models, Animal
KW - Ovariectomy
KW - Sheep
KW - Biomechanics/physiology
KW - Osteogenesis/physiology
KW - Osteoblasts/metabolism/pathology
KW - Bone and Bones/metabolism/pathology
KW - Bone Resorption/physiopathology
KW - Hypothalamus/physiology/surgery
KW - Osteoclasts/metabolism/pathology
KW - Osteoporosis/metabolism
KW - Pituitary Gland/physiology/surgery
U2 - 10.1002/jor.22327
DO - 10.1002/jor.22327
M3 - SCORING: Journal article
C2 - 23440966
VL - 31
SP - 1067
EP - 1074
JO - J ORTHOP RES
JF - J ORTHOP RES
SN - 0736-0266
IS - 7
M1 - 7
ER -