Large Animal Model of Osteoporotic Defect Healing: An Alternative to Metaphyseal Defect Model

Abstract

Osteoporosis is a common metabolic disorder diagnosed by lower bone density and higher risk of fracture. Fragility fractures because of osteoporosis are associated with high mortality rate. Deep understanding of fracture healing in osteoporosis is important for successful treatment. Therefore, the FDA approved the use of small and large animal models for preclinical testing. This study investigated the clinical relevance of a fracture defect model in the iliac crest of the osteoporotic sheep model and its several advantages over other models. The osteoporosis was achieved using ovariectomy (OVX) in combination with diet deficiency (OVXD) and steroid administration (OVXDS). Fluorochrome was injected to examine the rate of bone remodelling and bone mineralization. The defect areas were collected and embedded in paraffin and polymethyl metha acrylate (PMMA) for histological staining. OVXDS showed significantly lower bone mineral density (BMD) and bone mineral content (BMC) at all time points. Furthermore, variations in healing patterns were noticed, while the control, OVX and OVXD showed complete healing after 8 months. Bone quality was affected mostly in the OVXDS group showing irregular trabecular network, lower cortical bone thickness and higher cartilaginous tissue at 8 months. The mineral deposition rate showed a declining pattern in the control, OVX, and OVXD from 5 months to 8 months. One the contrary, the OVXDS group showed an incremental pattern from 5 months to 8 months. The defect zone in osteoporotic animals showed impaired healing and the control showed complete healing after 8 months. This unique established model serves as a dual-purpose model and has several advantages: no intraoperative and postoperative complications, no need for fixation methods for biomaterial testing, and reduction in animal numbers, which comply with 3R principles by using the same animal at two different time points.