Bone strength is an important clinical endpoint of osteoporosis research. The evaluation of the relative importance of bone and muscle components to bone strength has widespread implications for the understanding and preventing of osteoporosis. The objectives of this study were to understand the interrelationship between the different components of the muscular skeletal system and to determine the effect of forearm muscle size, forelimb grip strength, forearm bone mineral density (BMD), and forearm bone size on the humerus breaking strength among 10 inbred strains of mice. The forearm muscle size was measured using a peripheral quantitative computed tomography (pQCT). The forearm BMD and forearm bone size were measured using a PIXIMUS 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 grip strength, 0.76 for forearm muscle size, 0.6 for forearm BMD, 0.63 for forearm bone size, and 0.68 for humerus breaking strength. Forward stepwise multiregression analysis showed that the forearm BMD, forelimb grip strength, and forearm bone size were three major determinants of bone strength and explained 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.