Based on the mechanostat theory and the muscle-bone hypothesis, a methodological assessment of the musculoskeletal status in health and disease should relate maximum muscle force in relation to bone mass and geometry. While useful (i.e. three-dimensional) measures of tibial bone parameters can be obtained by peripheral quantitative computed tomography (pQCT), intrinsic plantarflexor muscle force cannot be directly measured under in vivo condition in humans. Instead, tissue size, torque and ground reaction force have been used as proxy markers of intrinsic muscle force. However, most of these proxy markers are not or insufficiently representative of maximum force. Based on our recent research, we describe a novel approach for the assessment of the lower leg muscle-bone unit in health and disease. It incorporates multiple one-legged hopping (m1LH) to assess maximum voluntary ground reaction force acting on the forefoot (F(m1LH)) and bone mineral content at the 14%-site of tibia length (vBMC(14%)) as assessed by pQCT. Using the quantitative relationship between these two variables in conjunction with F(m1LH) per body weight, we present a two-step quantitative diagnostic algorithm to discriminate between primary and secondary bone disorders in children and adults.