1. Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model
- Author
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Eik Vettorazzi, Ralf Oheim, F. Timo Beil, Anita Ignatius, Iain J. Clarke, Malte Steiner, Maciej J. K. Simon, Pia Pogoda, Florian Barvencik, and Michael Amling
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Hormone Replacement Therapy ,medicine.drug_class ,Ovariectomy ,medicine.medical_treatment ,Osteoporosis ,030209 endocrinology & metabolism ,Bone and Bones ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Bone Density ,Internal medicine ,medicine ,Animals ,Bone Resorption ,Reduction (orthopedic surgery) ,General Environmental Science ,Sheep ,business.industry ,Estrogens ,medicine.disease ,Skeleton (computer programming) ,Biomechanical Phenomena ,Disease Models, Animal ,Thyroxine ,030104 developmental biology ,Endocrinology ,Estrogen ,Pituitary Gland ,Ovariectomized rat ,General Earth and Planetary Sciences ,Female ,Hormone therapy ,business ,Hormone - 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.
- Published
- 2017