Is the Sheep the right model for osteoporosis research?Wednesday (28.09.2016) 15:45 - 16:00 Part of:
Osteoporosis is one of the main diseases diagnosed by bone loss using radiological parameter called T-score. The FDA guidelines recommend sheep as large animal model of osteoporosis. The study aims at recapitulating a clinically relevant sheep model of osteoporosis depending on the in vivo acquired T-score to assess fracture risk. The model suggests suitable treatment type and duration for future fracture healing studies in sheep. The study utilized Marino land sheep as a control to ovariectomy treatment. Ovariectomized sheep were divided into OVX alone, OVX with Vitamin D and Calcium deficient diet (OVXD) and additionally to the OVXD a steroid injection was given biweekly (OVXDS) group. Biopsies of the iliac crest were harvested at the beginning 0M, after 3M and after 8M. After Euthanasia fracture risk regions of the 3th lumbar vertebrae and of the distal femur were analyzed histologically. The IC biopsies showed significant lower proportion of osteoid/trabeculae bone after 3M and 8M than 0M in the control group and after 8M than 0M and 3M in the OVX group. The OVXDS group is the osteoid proportion significant higher after 8M than after 3M and 0M and significant higher after 3M than at time point 0M. At the time point 3M is the proportion of osteoid higher in the OVXDS group than in the control and OVX group. At the time point 8M is the proportion of osteoid significant higher than in all other groups. The osteoid proportion at the L3 is also significant higher in OVXDS than in all other groups and at the DF is OVXDS significant higher than control and OVX. Lower trabecular thickness and higher trabecular separation peaked at 8M in the OVXDS. Osteocytes were deformed and the lack of connectivity was present by the progression of the treatment in time and the compilation of the different osteoporosis induction methods. Bone dynamics show lower mineralization rate in the OVXD and OVDXS compared to the OVX and control. This was also seen in higher ALP activity area and increased osteoclast mediated resorption. The higher osteoid and ALP values with lower mineralization rate in OVXDS group reflect high bone metabolism. This effect can result from parathyroid hormone levels leading to a higher value of blood calcium but also a reduction of bone mineralization.