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02 October 2017 : Original article  

A New Clinically Relevant T-Score Standard to Interpret Bone Status in a Sheep Model

Christian Heiss1ABCDEFG, Stefanie Kern1CDEF, Deeksha Malhan1CDEF, Wolfgang Böcker12AB, Markus Engelhardt13AB, Diaa Eldin S. Daghma1AB, Sabine Stoetzel1BD, Jakob Schmitt1BCD, Matthias Ivo1BD, Vivien Kauschke1B, Katrin S. Lips1B, Kamen Tushtev4ABD, Kurosch Rezwan4ABDG, Thaqif El Khassawna1ABCDEFG*

DOI: 10.12659/MSMBR.905561

Med Sci Monit Basic Res 2017; 23:326-335

Abstract

BACKGROUND: 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

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416