ABSTRACT
BACKGROUND: Merino land sheep are a popular pre-clinical large animal model in research on systemic skeletal diseases such as osteoporosis. Interpretation of studies is difficult because many reference parameters are missing or not established. This study aims to determine the reference parameters of the skeletal system (peak bone mass = PBM, T-Score). A defined standard allows an easier comparison of the study data of the animal model with human studies (T-Score). MATERIALS AND METHODS: A total of 116 Dual Energy X-ray Absorptiometry DXA measurements were performed on 74 untreated sheep. The average age of the animals was 57 months. The BMD, BMC, and fat content of the sheep were determined by the relevant human region of interest (ROI). From this, the PBM and from this the T-score for each of the animals were calculated. RESULTS: Using 682 DXA measurements BMD and BMC were determined to provide an indication to PBM. For BMD a significant correlation to the age of the animals was observed (p = 0.043). A significant correlation was also seen for BMC (B) (p ≤ 0.001). In the age-dependent analysis, a widespread of values above the linear regression line was measured for both BMD and BMC between the 50th and 90th months of life. From an age of about 90 months, a wider spread of values below the linear regression line was found, although the average values continued to rise. DISCUSSION: The evaluation of the 116 DXA measurements allowed the determination of the PBM for merino land sheep. With the help of the PBM, a T-score was calculated for each animal. The statistical analysis shows significant differences in BMD values between the different animal groups in each of the four ROIs investigated. Individual control or sham groups per study are therefore not sufficient. To improve comparability, an independent reference group should be established. CONCLUSION: An independent reference group for PBM and a T-score was established from four to six-year-old animals. The bone density increases with the age of the animals. Around the fourth year of life, a first peak could be observed. Also, after the seventh year of life, a further peak with the beginning plateau phase was observed. When compiling a group of animals for an osteoporosis model, animals from the age of seven years should, therefore, be used.
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.
