ANIMAL MODELS for OSTEOPOROSIS

We have used rodents to study the effects of estrogens and androgens on the skeleton and compared the results with remodelling species such as primates (macaques) which have a skeleton very similar to humans. We have shown substantial differences between the two models especially in the cortical bone where ovariectomy induces profound changes in primates not seen in rodents. We have developed models of immobilization-induced osteoporosis in the dog and of inflammation-induced arthritis in the rabbit. We are exploring the hypothesis that if bone resorption is prevented by anti-resorptive drugs, the cartilage can also be protected in inflammatory arthritis.

Genetic diseases of the skeleton and transgenic animal models

We are studying the effects of inborn collagen defects on the mineralization and bone fragility in osteogenesis imperfecta where we find a profound decrease in mineral content. We are exploring the abnormality of mineral packing which underlie bone fragility in this disease. We are also investigating a mouse model where only half the type I collagen is produced and another mouse model where the genes encoding some non-collagenous proteins have been deleted, to try and understand the downstream effect of these proteins on mineral size, packing and chemistry.

Models of osteoarthritis

We are comparing human osteoarthritis (OA) with spontaneous OA in free-ranging rhesus monkeys from the Caribbean Primate Research Centre and with induced OA in the dog to try and understand the mechanisms of OA development. We have shown that in human OA the subchondral bone is thicker but undermineralized which may be due to mineralization changes which induce cartilage destruction. We have demonstrated that OA in the rhesus monkeys is similar to OA in humans both at the histological and chemical level. Finally, we are exploring changes in mineralization in human rheumatoid arthritis.