Variability in skeletal mass, structure, and biomechanical properties among inbred strains of rats

The aim of this study was to assess the usefulness of the inbred rat model for studies of genetic influences on skeletal fragility. We characterized bone mass, geometry, and skeletal biomechanics in 11 inbred strains of rats. This study showed that considerable variation exists in bone structure, areal bone mineral density (aBMD), and fragility phenotypes among inbred strains of rats. Interestingly, the variability in skeletal phenotypes in rats was site specific, suggesting that no single gene regulates skeletal fragility at all sites. For instance, the Copenhagen 2331 (COP) strain had the greatest biomechanical properties in the femoral neck but only modest bone strength at the femoral midshaft, compared with other strains. Consequently, COP rats appear to have alleles that specifically enhance femoral neck biomechanical properties and may serve as a model for studying genetic influences on hip strength. The Brown Norway (BN) and Fischer 344 (F344) strains may provide models for vertebral fragility because each has relatively fragile lumbar vertebrae. The F344 rats also had the most fragile femora and, thus, appear to carry alleles that cause overall skeletal fragility. We identified two inbred rat crosses that will facilitate the study of genetic influences on skeletal fragility at clinically relevant skeletal sites: Lewis (LEW) with F344 (primarily for vertebral fragility) and COP with DA (primarily for femoral neck fragility). The results strongly suggest that selected crosses of inbred strains of rats will provide useful models for studying genetic influences on bone strength and structure.