Quantitative assessment of forearm muscle size, forelimb grip strength, forearm bone mineral density, and forearm bone size in determining humerus breaking strength in 10 inbred strains of mice

Bone strength is an important clinical endpoint of osteoporosis research. T he evaluation of the relative importance of bone and muscle components to b one strength has widespread implications for the understanding and preventi ng of osteoporosis. The objectives of this study were to understand the int errelationship between the different components of the muscular skeletal sy stem and to determine the effect of forearm muscle size, forelimb grip stre ngth, forearm bone mineral density (BMD), and forearm bone size on the hume rus breaking strength among 10 inbred strains of mice. The forearm muscle s ize was measured using a peripheral quantitative computed tomography (pQCT) . The forearm BMD and forearm bone size were measured using a PIXIMUS (TM) Densitometer. The forelimb grip strength and humerus breaking strength were measured using an Instron Mechanical Tester. Significant correlations were found among the five regional phenotypes. All variables have a moderately high genetic component with heritability estimates of 0.83 for forelimb gri p strength, 0.76 for forearm muscle size, 0.6 for forearm BMD 0.63 for fore arm bone size, and 0.68 for humerus breaking strength. Forward stepwise mul tiregression analysis showed that the forearm BMD, forelimb grip strength, and forearm bone size were three major determinants of bone strength and ex plained 61% of the variation in bone breaking strength. These data suggest that evaluation of these three parameters together, rather than BMD alone, is a more effective, noninvasive approach for predicting fracture risk.