gms | German Medical Science

Objectives: Osteoporosis mostly affects women of post-menopausal age. It is characterized by a decrease in bone turnover and strength that predispose patients to increased risk of fracture. Several small animal models are available for studying fracture healing in osteoporotic bone. However, these models cannot reflect the true clinical situation seen in humans due to age and testable fracture size. Hence, the aim of this study is to establish and characterize an adult osteoporotic ovine model with a critical-sized metaphyseal defect that will be useful for studying fracture healing in osteoporotic bone

Methods: 12 adult Merino sheep aged 6 to 7 years were divided into two groups: 6 ovariectomized (OVX) and 6 sham-operated (SHAM) sheep. Osteoporosis was induced in the OVX through bilateral ovariectomy, multi-deficient diet and steroids while the SHAM group was fed with the standard diet. Bone mineral density (BMD) of the animals were measured before and 3 months after ovariectomy. A 10 mm wedge-shaped osteotomy stabilized with a titanium plate was created at the distal-metaphyseal area of the left femoral of the OVX and SHAM. 12 weeks post-surgery, the left and right femora were harvested and processed to study healing at the defect site.

Results and Conclusion: After three months of osteoporosis induction, a significant decrease was seen in the BMD of the pelvic, spine and femur regions of the OVX compared to those of the SHAM. Micro-computer tomography analysis showed that the defect area in the SHAM was medially bridged with soft tissue whereas that of the OVX had no bony bridging. Also, SHAM had denser trabecular architecture in contrast to decrease in trabecular number observed in the OVX. These observations were confirmed by histomorphometric and biomechanical analyses which revealed a decrease in bone formation and weakness in bone strength, respectively, in the OVX relative to the SHAM. Furthermore, gene expression quantification showed a decrease in the expression of prominent bone formation markers including osteocalcin, collagen-1 and bone-specific alkaline phosphatase in the OVX.

Our results indicate that a 10 mm metaphyseal femoral defect in adult osteoporotic sheep can serve as a clinically relevant large animal model to study metaphyseal bone healing and for testing of new orthopedic implants prior to clinical use in human.