The potential of sheep for the study of osteopenia: current status and comparison with other animal models.

There is a great need to develop an animal model for postmenopausal osteoporosis; a model that will be useful for the understanding of the pathogenesis of the disease as well as the investigation of new therapies. The requirements for such an animal model are discussed and ones that have been used in the past include nonhuman primates, dogs, cats, rodents, rabbits, guinea pigs, and minipigs. Advantages and disadvantages of these models are briefly reviewed. Sheep are a promising model for various reasons; they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and have hormone profiles similar to women. Ovariectomy results in a slight loss of bone from the ovine iliac crest, and biochemical markers such as osteocalcin are well characterized. Physiological disadvantages are lack of natural menopause, that normal estrus cycles are restricted to fall and winter and that they have a different gastrointestinal system. Sheep have cortical bone that is plexiform in structure although haversian remodeling is seen in older animals. When and if biomechanical incompetence of bone follows ovariectomy is presently unknown. There is no ideal model for the study of postmenopausal osteoporosis; all have advantages and disadvantages. Researchers in this field must recognize the limitations of the model they choose, and select one that will fulfill their needs.