Seasonal changes in bone metabolism in sheep: further characterization of an animal model for human osteoporosis.

The paper by Daniel Arens and colleagues, published in this issue of The Veterinary Journal, is one of several that are further characterising the sheep as a model for osteoporosis – a severe debilitating metabolic disease that affects mainly women (Arens et al., 2007). Why do we need an animal model for osteoporosis when there is an abundance of human subjects, especially as baby boomers age? Animal models have played an important role in history for the benefit of human health and greater understanding osteoporosis is just one of many examples of this. The ovariectomised rat has occupied a vital niche in the early screening of pharmaceutical agents for osteoporosis and the economics of research dictates the use of this model. However, if a particular compound is likely to help the human condition, a larger animal, higher up the phylogenetic scale – such as the aged ovariectomised ewe, will be needed before this drug can be used in a human clinical trial. The other need for a relatively large animal model with some of the characteristics of human osteoporosis, is the design of prosthetic devices (joint replacements, spinal instrumentation, external fixator pins, etc.), with different coatings to promote osseointegration. These devices must be able to perform and not loosen in the presence of decreased bone mass (Turner, 2002). Smaller sized animals (rats, mice and rabbits) cannot be used when implants of the size used in humans, must be tested. A variety of factors can cause bone loss in sheep. To mimic the human condition of post-menopausal osteoporosis, a number of studies in sheep from laboratories around the world initially investigated the effects of an acute estrogen deficiency associated with ovariectomy (Chavassieux, 1990; O’Connell, 1999; Turner et al., 1995). The results in from these studies were encouraging but it was clear that more information was necessary to characterize the model. Specifically, what information was missing from the sheep model that was well known in human osteoporosis? Corticosteroid-induced bone loss is seen in humans treated for allergies, rheumatoid arthritis, and asthma to name but a few. Subsequent to the studies of the effect of acute estrogen deficiency in sheep came work in search of better bone-sparing corticosteroids (O’Connell et al., 1993). This