Metaphyseal fracture healing in a sheep model of low turnover osteoporosis induced by hypothalamic-pituitary disconnection (HPD)

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 -