Variation in childhood skeletal robustness is an important determinant of cortical area in young adults

A better understanding of bone growth will benefit efforts to reduce fracture incidence, because variation in elderly bone traits is determined primarily by adulthood. The natural variation in robustness was used as a model to understand how variable growth patterns define adult bone morphology. Longitudinally acquired hand radiographs of 29 boys and 30 girls were obtained from the Bolton-Brush study for 6 time points spanning 8 to 18 years of age. Segregating individuals into tertiles based on robustness revealed that the biological activity underlying bone growth varied significantly with the natural variation in robustness. For boys, slender metacarpals used an osteoblast-dependent growth pattern to establish function, whereas robust metacarpals used an osteoclast-dependent growth pattern. In contrast, differences in biological activity between girls with slender and robust metacarpals were largely based on the age at which the marrow surface changed from expansion to infilling. Importantly, cortical area for slender metacarpals was as much as 19.7% and 32.2% lower than robust metacarpals for boys and girls, respectively, indicating that robustness was a major determinant of adult cortical area. Finally, after accounting for robustness and body weight effects, we found that the inter-individual variation in cortical area was established as early as 8 years of age. While variation in the amount of bone acquired during growth has primarily been attributed to factors like nutrition, exercise, and genetic background, we showed that the natural variation in robustness was also a major determinant of cortical area, which is an important determinant of bone mass. This predictable relationship between robustness and cortical area should be incorporated into clinical diagnostic measures and experimental studies.

► The biological activity underlying bone growth varied significantly with the natural variation in robustness. ► The prophylactic treatment aimed to increase bone mass during growth will benefit from knowledge of a child's robustness status. ► Cortical area was significantly lower for slender compared to robust metacarpals, indicating robustness is a major determinant of bone mass. ► Genetic analyses based on cortical area may find genes related to external size, since these traits covary in predictable ways. ► Variation in cortical area relative to bone robustness is established as early as 8 years of age, and possibly as early as 4 years.