Quantification of bone mineral density to define osteoporosis in rat

Abstract

The diagnosis of osteoporosis centers on assessment of bone mass and quality. In the absence of evidence-based guidelines to assess bone status in laboratory animals and unsuitability of use of T-/Z-scores meant for clinical application in animal studies, most investigators involved in new drug research and development employ clinical biomarkers and kits to assess bone turnover rate and portray change in bone mineral density (BMD) as percentage of increase/decrease, making comparative assessment of the effect highly impractical. This study proposes threshold boundaries of BMD (rT-score) in colony-bred Sprague-Dawley rats, distinct from those used clinically. Boundaries were obtained keeping fixed Type-I error (α=0.025). Femur neck was considered best for defining bone status using BMD measured by dual-energy X-ray absorptiometry. Findings demonstrate that BMD≤−1.96 rT-score signifies osteoporosis and BMD between >−1.96 and <−0.80 rT-score as osteopenia. Performance of boundaries to ascertain bone status was examined through simulation under different physiological/hormonal states viz. estrogen deficiency, ageing, estrus cycle, pregnancy, and lactation. The Area Under the Receiver Operating Characteristic curve of 0.98 obtained using BMD of femur neck, being close to unity, shows excellent ability of the proposed rT-score to effectively identify osteoporosis. Further studies using certain hierarchical measures of bone quality such as histomorphometry, mechanical testing etc. could supplement these findings. Since, unlike humans, most laboratory animals including rats only exhibit osteopenia and do not fracture their bones, the proposed thresholds are intended to serve as categorical tools to define bone quality and not to predict fracture risk.