The primary objective of my research program is to understand how complex adaptive systems like bone establish function during growth and maintain function during aging. Having a better understanding of how complex systems work will benefit efforts to reduce skeletal fracture risk by identifying the genetic and environmental factors that impair (or promote) specific components of the functional adaptation process and that compromise (or improve) fracture resistance.

Using a genetic randomization approach, my laboratory identified a pattern in the way skeletal traits covary across a population of recombinant inbred mouse strains. This line of research established that variation in bone morphology is functionally related to tissue-mineralization (tissue-quality). These functional interactions, known in the broader literature as phenotypic integration, are part of the functional adaptation process wherein mutations affecting external bone size are compensated by coordinated changes in tissue-quality. I have placed a large emphasis on translating the biological concepts learned from the mouse directly to the human skeleton, which shows similar functional trait interactions as the mouse skeleton. Further, we demonstrated that individuals are at risk of developing an insufficiency fracture for different biomechanical reasons. Importantly, studies of the mouse and human skeletons have shown that functional interactions among adult traits are established by 2-4 weeks of age in the mouse and by 4 years in humans. This latter research effort is the reason why a major focus of my lab involves studying how and when these functional interactions arise during postnatal growth. I expect that genetic or environmental perturbations expressed during this critical window will impair the development of bone strength and lead to increased fracture risk later in life.
Recently, my lab discovered a novel association between a measure of external bone size and the internal remodeling process that is central to establishing and maintaining bone strength. This observation motivated us to apply what we learned thus far in complex adaptive systems and to conduct an analysis of secondary data utilize existing longitudinally acquired human data to test whether individuals with narrow bones would show age-related changes in bone structure and strength that differed from individuals with wide bones. Examination of 14 year changes in BMC, bone area and BMC indeed revealed that women with narrow femoral necks showed small reductions in BMC (consistent with having a lower baseline level of intra-cortical remodeling) but large increases in bone area. In contrast, women with wide femoral necks showed large reductions in BMC (consistent with having a higher baseline level of intra-cortical remodeling) but only small increases in bone area. Our current research efforts are directed toward better understanding how external-size dependent changes in structure and mass affect bone strength and thus create different strength-decline trajectories during the menopausal transition. Better understanding this global-level regulation of intra-cortical remodeling may be critically important for developing prophylactic treatments for reducing stress (insufficiency) and fragility fractures that are personalized to the biological needs of the individual. Together, these studies have demonstrated how a simple measure like external bone size can help predict how bones grow and age.