Colocalization between bone loading and metabolic activity in the human tibia in response to acute exercise

Abstract

Bone strain and remodeling are important factors for bone health. Improved characterization of relationships between these factors in response to acute loading will improve our understanding of bone maintenance, adaptation to load, and pathophysiology. The purpose of this study was to evaluate colocalization between finite-element-estimated bone strain and [18F]sodium fluoride positron emission tomography imaging-estimated subchondral bone remodeling in the tibial diaphysis in response to acute exercise. We hypothesized that the exercise-induced change in standardized uptake values would be greatest in regions of higher strain. 26 participants underwent bilateral positron emission tomography/magnetic resonance scans before and after a bout of stair ascent and descent exercise. Finite element analysis was performed to calculate principal strain distributions in the tibial diaphysis. [18F]sodium fluoride standardized uptake values were calculated from pre- and post-exercise positron emission tomography data and mapped to the tibial surface. Mean pre-exercise and exercise-induced change in standardized uptake values were calculated and compared between regions defined by strain percentile. Both normalized mean pre-exercise and exercise-induced change in standardized uptake values increased with maximum principal strain in a pattern suggesting an exponential relationship. Pre-exercise and exercise-induced change in standardized uptake value were notably much greater in the region of highest maximum principal strains (estimated marginal means = 76.9 and 71.0 percentile, respectively) when compared to all other regions of the tibial diaphysis ([≤] 61.1 and [≤] 57.0 percentile, respectively, p < 0.001). This study is the first to directly show a relationship between bone mechanical loads and acute [18F]sodium fluoride uptake in humans in vivo. Our results highlight the influence of tensile strain magnitude on bone metabolic activity in response to acute loading. Furthermore, we demonstrate the utility of a combined finite element analysis and positron emission tomography approach to interrogate relationships between bone loading and bone metabolic response to acute exercise.