THE FERRET AS A SMALL ANIMAL-MODEL WITH BMU-BASED REMODELING FOR SKELETAL RESEARCH

The need exists for a small animal model with bone metabolic unit (BMU )-based remodeling to mimic the bone loss found in postmenopausal wome n. The purpose of this investigation was to evaluate the ferret as a p otential model for skeletal research. Specifically, we determined whet her the ferret: 1) exhibits evidence of BMU-remodeling, 2) has a skele tal response to parathyroid hormone (PTH) similar to other remodeling species, and 3) loses bone in response to reduced estrogen levels. Met hods: Using three sets of experiments, we determined the response of f emale ferrets to ovariectomy/light cycle manipulation or to administra tion of PTH. Scanning electron microscopy, light microscopy, determina tion of estrogen levels and/or single-photon absorptiometry (SPA) were used for evaluation. Results: The ferret was found to exhibit BMU-bas ed remodeling, and may therefore provide a small animal remodeling spe cies for skeletal research. Ferrets reach skeletal maturity between fo ur and seven months of age as evidenced by closure of the growth plate and maturation of trabecluae from thin rods to thick rods and plates. PTH treatment resulted ina marked increase in bone mass accompanied b y the PTH-induced tunneling phenomenon known to occur in dogs and huma ns but not rats. The response to PTH supports the use of the ferret in studies of bone anabolic agents. Bone mass in the proximal tibia was significantly reduced when estrogen depletion was induced by either bi lateral ovariectomy or short light/dark cycles (8 hour light, 16 hour dark). Maintenance of intact ferrets under short-light conditions mimi ced ovariectomy in terms of serum estrogen levels, uterine weights, an d tibial BMD. The bone loss seen following ovariectomy or short light/ dark cycles suggests the ferret as a model for evaluating the effects of estrogen-depletion in a remodeling skeleton. Alteration of light-cy cles may offer a reversible alternative to surgical induction of estro gen depletion. Conclusions: Based on these observations, we conclude t hat the ferret may offer an exciting new model for skeletal research.