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 b one mass, geometry, and skeletal biomechanics in 11 inbred strains of rats. This study showed that considerable variation exists in bone structure, ar eal bone mineral density (aBMD), and fragility phenotypes among inbred stra ins of rats. Interestingly, the variability in skeletal phenotypes in rats was site specific, suggesting that no single gene regulates skeletal fragil ity at all sites. For instance, the Copenhagen 2331 (COP) strain had the gr eatest biomechanical properties in the femoral neck but only modest bone st rength at the femoral midshaft, compared with other strains. Consequently, COP rats appear to have alleles that specifically enhance femoral neck biom echanical properties and may serve as a model for studying genetic influenc es on hip strength. The Brown Norway (BN) and Fischer 344 (F344) strains ma y provide models for vertebral fragility because each has relatively fragil e lumbar vertebrae. The F344 rats also had the most fragile femora and, thu s, appear to carry alleles that cause overall skeletal fragility. We identi fied two inbred rat crosses that will facilitate the study of genetic influ ences on skeletal fragility at clinically relevant skeletal sites: Lewis (L EW) with F344 (primarily for vertebral fragility) and COP with DA (primaril y for femoral neck fragility). The results strongly suggest that selected c rosses of inbred strains of rats will provide useful models for studying ge netic influences on bone strength and structure.