Testing the Functional Model of Bone Development: Direct and Mediating Role of Muscle Strength on Bone Properties in Growing Youth Ludwa, Izabella A. Gracia Marco, Luis Andrés Children Bone development Muscle strength Radial speed of sound Tibial speed of sound Bone turnover This study examines the functional model of bone development in peri-pubertal boys and girls. Specifically, we implemented a mixed-longitudinal design and hierarchical structural models to provide experimental evidence in support of the conceptual functional model of bone development, postulating that the primary mechanical stimulus of bone strength development is muscle force. To this end, we measured radial and tibial bone properties (speed of sound, SOS), isometric grip and knee extensors strength, bone resorption (urinary NTX concentration), body mass index (BMI), somatic maturity (years from peak height velocity) and skeletal maturity (bone age) in 180 children aged 8–16 years. Measurements were repeated 2–4 times over a period of 3 years. The multilevel structural equation modeling of 406 participant-session observations revealed similar results for radial and tibial SOS. Muscle strength (i.e., grip strength for the radial and knee extension for tibial model) and NTX have a significant direct effect on bone SOS (β = 0.29 and −0.18, respectively). Somatic maturity had a direct impact on muscle strength (β = 0.24) and both a direct and indirect effect on bone SOS (total effect, β = 0.30). Physical activity and BMI also had a significant direct impact on bone properties, (β = 0.06 and −0.18, respectively), and an additional significant indirect effect through muscle strength (β = 0.01 and 0.05, respectively) with small differences per bone site and sex. Muscle strength fully mediated the impact of bone age (β = 0.14) while there was no significant effect of energy intake on either muscle strength or bone SOS. In conclusion, our results support the functional model of bone development in that muscle strength and bone metabolism directly affect bone development while the contribution of maturity, physical activity, and other modulators such as BMI, on bone development is additionally modulated through their effect on muscle strength. 2021-05-24T12:24:09Z 2021-05-24T12:24:09Z 2021 journal article Ludwa, I.A.; Mongeon, K.; Sanderson, M.; Gracia Marco, L.; Klentrou, P. Testing the Functional Model of Bone Development: Direct and Mediating Role of Muscle Strength on Bone Properties in Growing Youth. Int. J. Environ. Res. Public Health 2021, 18, 3154. https://doi.org/10.3390/ijerph 18063154 http://hdl.handle.net/10481/68687 10.3390/ijerph18063154 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI