[Show abstract][Hide abstract] ABSTRACT: A better understanding of femoral neck structure and age-related bone loss will benefit research aimed at reducing fracture risk. We used the natural variation in robustness (bone width relative to length) to analyze how adaptive processes covary traits in association with robustness, and whether the variation in robustness affects age-related bone loss patterns. Femoral necks from 49 female cadavers (29-93 years of age) were evaluated for morphological and tissue-level traits using radiography, peripheral quantitative computed tomography, micro-computed tomography, and ash-content analysis. Femoral neck robustness was normally distributed and varied widely with a coefficient of variation of 14.9%. Age-adjusted partial regression analysis revealed significant negative correlations (p < 0.05) between robustness and relative cortical area, cortical tissue-mineral density (Ct.TMD), and trabecular bone mineral density (Ma.BMD). Path analysis confirmed these results showing that a one standard deviation (SD) increase in robustness was associated with a 0.70 SD decrease in RCA, 0.47 SD decrease in Ct.TMD, and 0.43 SD decrease in Ma.BMD. Significantly different bone loss patterns were observed when comparing the most slender and most robust tertiles. Robust femora showed significant negative correlations with age for cortical area (R(2) = 0.29, p < 0.03), Ma.BMD (R(2) = 0.34, p < 0.01), and Ct.TMD (R(2) = 0.4, p < 0.003). However, slender femora did not show these age-related changes (R(2) < 0.09, p > 0.2). The results indicated that slender femora were constructed with a different set of traits compared to robust femora, and that the natural variation in robustness was a determinant of age-related bone loss patterns. Clinical diagnoses and treatments may benefit from a better understanding of these robustness-specific structural and aging patterns.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 07/2012; 27(7):1501-10. DOI:10.1002/jbmr.1614 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Bone 07/2011; 49(4):799-809. DOI:10.1016/j.bone.2011.07.018 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adults acquire unique sets of morphological and tissue-quality bone traits that are predictable based on robustness and deterministic of strength and fragility. How and when individual trait sets arise during growth has not been established. Longitudinal structural changes of the metacarpal diaphysis were measured for boys and girls from 3 mo to 8 yr of age using hand radiographs obtained from the Bolton-Brush collection. Robustness varied approximately 2-fold among boys and girls, and individual values were established by 2 yr of age, indicating that genetic and environmental factors controlling the relationship between growth in width and growth in length were established early during postnatal growth. Significant negative correlations between robustness and relative cortical area and a significant positive correlation between robustness and a novel measure capturing the efficiency of growth indicated that coordination of the subperiosteal and endocortical surfaces was responsible for this population acquiring a narrow range of trait sets that was predictable based on robustness. Boys and girls with robust diaphyses had proportionally thinner cortices to minimize mass, whereas children with slender diaphyses had proportionally thicker cortices to maximize stiffness. Girls had more slender metacarpals with proportionally thicker cortices compared with boys at all prepubertal ages. Although postnatal growth patterns varied in fundamentally different ways with sex and robustness, the dependence of trait sets on robustness indicated that children sustained variants affecting subperiosteal growth because they shared a common biological factor regulating functional adaptation. Considering the natural variation in acquired trait sets may help identify determinants of fracture risk, because age-related bone loss and gain will affect slender and robust structures differently.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 12/2009; 24(12):1969-80. DOI:10.1359/jbmr.090525 · 6.83 Impact Factor