Variability in Skeletal Mass, Structure, and Biomechanical Properties Among Inbred Strains of Rats

Abstract

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.

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

“…The Lewis and Fischer inbred rat strains have been used as a model of human aging-related traits [10][11][12] including an intercross genome screening study of bone properties [13]. The power of the mouse as a genetic tool has been utilized to uncover genes whose normal allelic variation regulates BMD and other skeletal traits such as bone geometry, microarchitecture and strength [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

Breast tumors induced by N-methyl-N-nitrosourea are damaging to bone strength, structure, and mineralization in the absence of metastasis in rats

“…We are aware of no influence of MNU per se on bone tissue in the available literature, and our mechanical strength parameters appear to be within the ranges reported for various rat strains reported by Turner and colleagues. (19) In summary, we observed moderate and statistically significant degradation of bone mineralization, strength, and structure in the femurs of rats developing breast tumors in response to MNU injection relative to injected rats without tumors. These changes occurred in the absence of metastasis to bone tissue over a 10-week period from injection.…”

“…Following fracture, digital calipers were used to measure the span of the cross section of the fracture site along anteroposterior and mediolateral axes, as well as the thickness of the cortical shell at four points defined as the midpoints of the cortical rim in the four quadrants of the cross section created by the anteroposterior and mediolateral planes. These parameters were used to approximate the cross-sectional moment of inertia I at the fracture site using an elliptical model according to the methods described by Turner and colleagues (19) :…”

“…(19) Following bend testing, the proximal end of the femur was mounted vertically in a chuck for mechanical testing of the femoral neck to failure. Load was applied at 0.6 mm/min at the superior edge of the femoral head in a direction parallel to the shaft of the femur.…”

“…Because of the irregular and nonuniform nature of the femoral neck test, no attempt was made to normalize femoral neck data to the size and form of the neck. (19) Bone structure…”