Advancing Individualized Medicine by Understanding Phenotypic Integration Using the Human Skeleton as a Model System
Abstract
Susceptibility to common, heritable diseases is generally thought to originate at the genetic-level, and most studies seek genomic variants or altered molecular networks to develop novel diagnostics and treatments to reduce disease risk on a personalized basis. We show that fracture susceptibility in human tibiae and femora can also arise at a higher-level of biological organization, a phenomenon that may be difficult to predict from genetic information alone, because it involved biomechanical tradeoffs, constraints on cellular activity, and a network of compensatory trait interactions defining organ-level function. Importantly, we also identified a novel level of biological control regulating the degree of internal remodeling affecting young adult tibiae and aging femora. Limited compensation at this level of biological organization may be a public health concern, not only because of the increased fracture susceptibility, but also because it is unclear to what extent prophylactic treatments can circumvent intrinsic cellular constraints to establish a higher degree of functional equivalence among individuals. Thus, the funds supporting our research efforts have significantly advanced our understanding of bone by identifying a "flaw" or limitation in the functional adaptation process that may contribute to fracture risk and by discovering biological controls regulating internal remodeling that have not previously been reported.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA581691
Entities
People
- Karl J. Jepsen
Organizations
- Mount Sinai Hospital