Large animal model for osteoporosis in humans: the ewe
R Oheim1, M Amling, A Ignatius
1Department of Osteology and Biomechanics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Abstract:
Osteoporosis is a chronic systemic disease characterised by bone loss and microarchitectural deterioration. Since the underlying regulatory mechanisms are still not fully understood and treatment options are not satisfactorily resolved, massive efforts are underway to further investigate this critical illness. Large animal models are stipulated, e.g. by the Food and Drug Administration, for preclinical prevention and intervention studies related to osteoporosis research; in this context, the ewe has already proven its value for orthopaedic research. Although oestrogen deficiency doubtless influences bone metabolism in sheep, the ovariectomised ewe seems unsuitable as a model for postmenopausal osteoporosis and bone loss induction due to its unreliable impact on bone mass and structure. In contrast, glucocorticoid treatment has a major impact on bone turnover and leads to bone conditions comparable to those found in steroid-treated humans. However, adverse side effects can be dramatic resulting in unacceptable discomfort and illness of the experimental animals. Further improvements are therefore essential to judge this model as ethically appropriate. Additionally, models for osteoporosis induced by surgical interventions of central regulatory mechanisms seem to be attractive, as remarkable bone loss is induced by only one surgical procedure without any further treatment. Taken together, different ewe models for osteoporosis have been successfully established and are invaluable for orthopaedic research. However, the search for a 'perfect' large remodelling animal model - in terms of mimicking the human disease and compatibility of bone loss, and without ethical concerns - is still on-going.
Insights
Developing effective osteoporosis treatments requires reliable animal models. While ewe models show promise for orthopedic research, current methods like ovariectomy or glucocorticoid treatment have limitations, necessitating ongoing research for an ideal model.
Area of Science:
- Orthopedics
- Endocrinology
- Veterinary Medicine
Background:
- Osteoporosis is a complex bone disease with poorly understood mechanisms and limited treatments.
- Large animal models are crucial for preclinical osteoporosis research, with ewes being valuable in orthopedics.
- Existing ewe models for osteoporosis have limitations, impacting their suitability and ethical considerations.
Purpose of the Study:
- To evaluate the suitability of different ewe models for studying osteoporosis.
- To identify the strengths and weaknesses of current large animal models for bone loss research.
- To guide the development of improved, ethically sound animal models for osteoporosis.
Main Methods:
- Review of existing literature on ewe models for osteoporosis research.
- Analysis of ovariectomy and glucocorticoid treatment models in ewes.
- Consideration of surgical intervention models for inducing bone loss.
Main Results:
- Ovariectomized ewe models show unreliable effects on bone mass and structure for postmenopausal osteoporosis.
- Glucocorticoid treatment induces bone changes comparable to humans but causes significant adverse effects.
- Surgical induction of central regulatory mechanism disruption shows potential for significant bone loss.
Conclusions:
- Various ewe models have been established and are valuable for orthopedic research.
- No single ewe model perfectly replicates human osteoporosis while remaining ethically sound.
- Continued research is essential to develop an ideal large animal model for osteoporosis.
