Christian Heiss, Stefanie Kern, Deeksha Malhan, Wolfgang Böcker, Markus Engelhardt, Diaa Eldin S. Daghma, Sabine Stoetzel, Jakob Schmitt, Matthias Ivo, Vivien Kauschke, Katrin S. Lips, Kamen Tushtev, Kurosch Rezwan, Thaqif El Khassawna
Department of Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University, Giessen, Germany
Med Sci Monit Basic Res 2017; 23:326-335
Available online: 2017-10-02
Osteoporosis is diagnosed by bone loss using a radiological parameter called T-score. Preclinical studies use DXA to evaluate bone status were the T-score is referenced on bone mineral density (BMD) values of the same animals before treatment. Clinically, the reference BMD represents values of an independent group of healthy patients around 30 years old. The present study established a clinically similar T-score standard to diagnose osteoporosis in a sheep model.
MATERIAL AND METHODS: We used 31 female merino land sheep (average 5.5 years old) to study osteoporosis. The following groups were compared using DXA measurement: 1) control; 2) ovariectomized (OVX); 3) OVX combined with a deficient diet (OVXD); and 4) OVXD combined with methylprednisolone administration (OVXDS). Further, an independent group of 32 healthy sheep (4–6 years old) were measured as an independent baseline. BMD was measured at 0 months, 3 months, and 8 months after treatment.
RESULTS: The same significance pattern between the treated groups and either baseline groups was seen. However, using an independent baseline changed the “clinical” interpretation of the data from an osteoporotic bone status (T-score <–2.5) after 3 months of OXDS treatment into an osteopenic bone status (T-score <–1.5 to –2.4).
CONCLUSIONS: Using an independent baseline enhanced the statistical significance and showed the clinical relevance. Furthermore, an independent baseline is a reliable alternative to use of a new control group for future experiments and thus reduces the number of animals needed by eliminating the need for a control and corresponding to clinical practice.
Keywords: Animal Testing Alternatives, Bone Diseases, Metabolic, Databases as Topic, Osteoporosis