CALCIUM-RESTRICTED OVARIECTOMIZED SINCLAIR S-1 MINIPIGS - AN ANIMAL-MODEL OF OSTEOPENIA AND TRABECULAR PLATE PERFORATION

The ovariectomized rat model has now been generally accepted as a usef ul model for screening different therapeutic agents, but there is a ma jor requirement to identify reliable large animal models for osteoporo sis research. In this study, the calcium restricted, ovariectomized mi nipig has been thoroughly investigated in order to define a large anim al model with trabecular and cortical bone remodeling which would be r eliable for further testing of agents that had shown promise of effica cy during the screening procedure. Twenty six female, 4-month old mini pigs were randomized into four groups and fed either normal diet (0.90 % calcium (Ca.)) or diet with restricted calcium content (0.75%, 0.50% ). At the age of ten months, 3 groups were ovariectomized (OVX) while one group on normal diet was shamoperated. The groups were followed fo r six months after the operation. At death, bone mass was determined b y densitometry and by ashing. Additionally, biomechanical competence w as assessed in trabecular bone cores from the vertebral bodies. Finall y, histomorphometry (static and dynamic parameters) and structural ana lyses (star volume) were performed on the vertebral bodies. The study revealed an OVX-related decline of 6% in vertebral bone mineral densit y (BMD) and a decline of 15% in trabecular bone volume (BV/TV). In con trast, a 15% increase in mean trabecular plate separation (Tb.Sp.) and a small increase in marrow space star volume (Ma. Star V.) were detec ted. The structural changes became more pronounced when OVX was combin ed with mild Ca. restriction (0.75% Ca.) with an increase in Ma. Star V. to 164%. By using a higher degree of Ca. restriction (0.50%), all t he described changes in bone mass and structure were blunted. ne biome chanical data followed the same pattern with a progressive decrease fr om the .90% Ca. sham-operated through the 0.90% OVX and to the 0.75% C a. OVX group and then an increase. It is concluded that the OVX minipi g on a 0.75% calcium-restricted diet promises to be a useful large ani mal model for osteoporosis research.