Metaphyseal fracture healing in a sheep model of low turnover osteoporosis induced by hypothalamic-pituitary disconnection (HPD)
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Metaphyseal fracture healing in a sheep model of low turnover osteoporosis induced by hypothalamic-pituitary disconnection (HPD). / Bindl, Ronny; Oheim, Ralf; Pogoda, Pia; Beil, Frank Timo; Gruchenberg, Katharina; Reitmaier, Sandra; Wehner, Tim; Calcia, Enrico; Radermacher, Peter; Claes, Lutz; Amling, Michael; Ignatius, Anita.
In: J ORTHOP RES, Vol. 31, No. 11, 01.11.2013, p. 1851-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Metaphyseal fracture healing in a sheep model of low turnover osteoporosis induced by hypothalamic-pituitary disconnection (HPD)
AU - Bindl, Ronny
AU - Oheim, Ralf
AU - Pogoda, Pia
AU - Beil, Frank Timo
AU - Gruchenberg, Katharina
AU - Reitmaier, Sandra
AU - Wehner, Tim
AU - Calcia, Enrico
AU - Radermacher, Peter
AU - Claes, Lutz
AU - Amling, Michael
AU - Ignatius, Anita
N1 - © 2013 Orthopaedic Research Society.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - We recently established a large animal model of osteoporosis in sheep using hypothalamic-pituitary disconnection (HPD). As central regulation is important for bone metabolism, HPD-sheep develop severe osteoporosis because of low bone turnover. In this study we investigated metaphyseal fracture healing in HPD-sheep. To elucidate potential pathomechanisms, we included a treatment group receiving thyroxine T4 and 17β-estradiol. Because clinically osteoporotic fractures often occur in the bone metaphysis, HPD-sheep and healthy controls received an osteotomy in the distal femoral condyle. Half of the HPD-sheep were systemically treated with thyroxine T4 and 17β-estradiol during the healing period. Fracture healing was evaluated after 8 weeks using pQCT, µCT, and histomorphometrical analysis. Bone mineral density (BMD) and bone volume/total volume (BV/TV) were considerably reduced by 30% and 36%, respectively, in the osteotomy gap of the HPD-sheep compared to healthy sheep. Histomorphometry also revealed a decreased amount of newly formed bone (-29%) and some remaining cartilage in the HPD-group, suggesting that HPD disturbed fracture healing. Thyroxine T4 and 17β-estradiol substitution considerably improved bone healing in the HPD-sheep. Our results indicate that fracture healing requires central regulation and that thyroxine T4 and 17β-estradiol contribute to the complex pathomechanisms of delayed metaphyseal bone healing in HPD-sheep.
AB - We recently established a large animal model of osteoporosis in sheep using hypothalamic-pituitary disconnection (HPD). As central regulation is important for bone metabolism, HPD-sheep develop severe osteoporosis because of low bone turnover. In this study we investigated metaphyseal fracture healing in HPD-sheep. To elucidate potential pathomechanisms, we included a treatment group receiving thyroxine T4 and 17β-estradiol. Because clinically osteoporotic fractures often occur in the bone metaphysis, HPD-sheep and healthy controls received an osteotomy in the distal femoral condyle. Half of the HPD-sheep were systemically treated with thyroxine T4 and 17β-estradiol during the healing period. Fracture healing was evaluated after 8 weeks using pQCT, µCT, and histomorphometrical analysis. Bone mineral density (BMD) and bone volume/total volume (BV/TV) were considerably reduced by 30% and 36%, respectively, in the osteotomy gap of the HPD-sheep compared to healthy sheep. Histomorphometry also revealed a decreased amount of newly formed bone (-29%) and some remaining cartilage in the HPD-group, suggesting that HPD disturbed fracture healing. Thyroxine T4 and 17β-estradiol substitution considerably improved bone healing in the HPD-sheep. Our results indicate that fracture healing requires central regulation and that thyroxine T4 and 17β-estradiol contribute to the complex pathomechanisms of delayed metaphyseal bone healing in HPD-sheep.
KW - Animals
KW - Disease Models, Animal
KW - Estradiol
KW - Fracture Healing
KW - Hypothalamus
KW - Osteoporotic Fractures
KW - Pituitary Gland
KW - Sheep
KW - Thyroxine
U2 - 10.1002/jor.22416
DO - 10.1002/jor.22416
M3 - SCORING: Journal article
C2 - 23813786
VL - 31
SP - 1851
EP - 1857
JO - J ORTHOP RES
JF - J ORTHOP RES
SN - 0736-0266
IS - 11
ER -