A new metaphyseal bone defect model in osteoporotic rats to study biomaterials for the enhancement of bone healing in osteoporotic fractures

作者：Alt Volker^*; Thormann Ulrich; Ray Seemun; Zahner Daniel; Duerselen Lutz; Lips Katrin; El Khassawna Thaqif; Heiss Christian; Riedrich Alina; Schlewitz Gudrun; Ignatius Anita; Kampschulte Marian; von Dewitz Helena; Heinemann Sascha; Schnettler Reinhard; Langheinrich Alexander

来源：Acta Biomaterialia, 2013, 9(6): 7035-7042.

DOI：10.1016/j.actbio.2013.02.002

• Biomaterials
• Osteoporosis
• Fracture healing
• Critical size defect

The intention of this study was to establish a new critical size animal model that represents clinically relevant situations with osteoporotic bone status and internally fixated metaphyseal defect fractures in which biomaterials for the enhancement of fracture healing in osteoporotic fracture defects can be studied. Twenty-eight rats were ovariectomized (OVX) and treated with a calcium-, phosphorus-, vitamin D3-, soy- and phytoestrogen-free diet. After 3 months Dual-energy X-ray absorptiometry measurements showed statistically significant reductions in bone mineral density of the spine of -25.9% and of the femur of -21.3% of the OVX rats compared with controls, confirming osteoporosis in the OVX rats. The OVX rats then underwent either 3 or 5 mm wedge-shaped osteotomy of the distal metaphyseal area of the femur that was internally stabilized with a T-shaped mini-plate. After 42 days biomechanical testing yielded completely unstable conditions in the 5 mm defect femora (bending stiffness 0 N mm(-2)) and a bending stiffness of 12,500 N mm(-2) in the 3 mm defects, which showed the beginning of fracture consolidation. Micro-computed tomography showed statistically significant more new bone formation in the 3 mm defects (4.83 +/- 0.37 mm(2)), with bridging of the initial fracture defect area, compared with the 5 mm defects (2.68 +/- 0.34 mm(2)), in which no bridging of the initial defect was found. These results were confirmed by histology. In conclusion, the 5 mm defect can be considered as a critical size defect model in which biomaterials can be tested.

• 出版日期2013-6