Ovariectomy-induced model of osteoporosis in pigs

Osteopathologies in humans, such as osteoporosis, rhematoid arthritis, and Pagets disease, are increasingly becoming a focus of biomedical and clinical research, which can in part be attributed to the awareness of the crosslinks between the immune and the skeletal systems. The area of osteoimmunology offers new therapeutic opportunities in the fight against disorders of the skeletal system, as exemplified by the use of anti-TNF-alpha antibodies in the treatment of rheumatoid arthritis. Animal models of diverse osteopathologies, such as osteoporosis, are mainly based on rodent models and are the basis for clinically based experiments dealing with this subject. Nevertheless, there is a need for large animal models, also because the FDA guidelines on osteoporosis research (1994) require data from both the rat and a larger species. Pigs would account for such a large animal model for several reasons, for example because of the well developed Haversian system, which is absent in rats. Aim of our study is the characterization of an ovariectomy-based porcine osteoporosis model. Other authors already did research on this subject, but they largely used growing minipigs, which I. due to their age, and II. due to breed-dependent properties (chondrodystrophic dwarfs) may not be an ideal model for (especially postmenopausal) osteoporosis. Therefore, we chose to use conventional adult sows as basis for our model. Another main difference to other groups is the fact, that we put great emphasis on the characterization of osteoimmunological properties, as it is already known, that osteopathological disorders, such as osteoporosis, significantly influence the immune system and vice versa. Four groups of 8 Large White sows each will be included (1. sham-OVX, 0.8 % Ca; 2. sham- OVX, 0.5 % Ca; 3. OVX, 0.8 % Ca; 4. OVX, 0.5 % Ca). Half of each group will be sacrificed 6 and the other half 12 months after start of the experiment. Laboratory investigations will be performed at day 0 (FACS analyses and serum bone metabolism markers) and at 6 and 12 months post OVX, including gross pathology, biomechanical testing, DEXA and microCT analyses, dynamic histomorphometry, bone ash analysis, serum levels of diverse bone metabolism- associated markers, such as RANKL, PTH, osteocalcin, and crosslaps, cytokine analyses, peripheral leukocyte surface marker expression analysis, osteoblast/osteoclast formation assays and analysis of osteoblast-specific markers, such as runx2, osterix, and RANKL. Given, that the disease dynamics of the proposed model are modulated by standard treatment regimens, namely bisphosphonate applications, accordingly to postmenopausal osteoporosis, which would have to be tested in a following study, this model can be used for testing new therapeutic strategies in the fight against osteoporosis.

Osteopathologies in humans, such as osteoporosis, rhematoid arthritis, and Paget`s disease, are increasingly becoming a focus of biomedical and clinical research, which can in part be attributed to the awareness of the crosslinks between the immune and the skeletal systems. The area of osteoimmunology offers new therapeutic opportunities in the fight against disorders of the skeletal system, as exemplified by the use of anti-TNF-alpha antibodies in the treatment of rheumatoid arthritis. Animal models of diverse osteopathologies, such as osteoporosis, are mainly based on rodent models and are the basis for clinically based experiments dealing with this subject. Nevertheless, there is a need for large animal models, also because the FDA guidelines on osteoporosis research (1994) require data from both the rat and a larger species. Pigs would account for such a large animal model for several reasons, for example because of the well developed Haversian system, which is absent in rats. Aim of our study is the characterization of an ovariectomy-based porcine osteoporosis model. Other authors already did research on this subject, but they largely used growing minipigs, which I. due to their age, and II. due to breed-dependent properties (chondrodystrophic dwarfs) may not be an ideal model for (especially postmenopausal) osteoporosis. Therefore, we chose to use conventional adult sows as basis for our model. Another main difference to other groups is the fact, that we put great emphasis on the characterization of osteoimmunological properties, as it is already known, that osteopathological disorders, such as osteoporosis, significantly influence the immune system and vice versa. Four groups of 8 Large White sows each will be included (1. sham-OVX, 0.8 % Ca; 2. sham- OVX, 0.5 % Ca; 3. OVX, 0.8 % Ca; 4. OVX, 0.5 % Ca). Half of each group will be sacrificed 6 and the other half 12 months after start of the experiment. Laboratory investigations will be performed at day 0 (FACS analyses and serum bone metabolism markers) and at 6 and 12 months post OVX, including gross pathology, biomechanical testing, DEXA and microCT analyses, dynamic histomorphometry, bone ash analysis, serum levels of diverse bone metabolism- associated markers, such as RANKL, PTH, osteocalcin, and crosslaps, cytokine analyses, peripheral leukocyte surface marker expression analysis, osteoblast/osteoclast formation assays and analysis of osteoblast-specific markers, such as runx2, osterix, and RANKL. Given, that the disease dynamics of the proposed model are modulated by standard treatment regimens, namely bisphosphonate applications, accordingly to postmenopausal osteoporosis, which would have to be tested in a following study, this model can be used for testing new therapeutic strategies in the fight against osteoporosis.