Sundar Srinivasan, Ph.D.
Dept. of Orthopaedics & Sports Medicine
Orthopaedic Science Laboratories
"Functional Adaptation in Bone: Modeling, In Vivo Manifestations and
Back"
ABSTRACT
A focus of our laboratory is to understand how bone cells and tissues
perceive and respond to mechanical stimuli and lack thereof. For
instance, we seek to understand how exercise makes bone bigger and
stronger and why disuse accompanying bed rest or space flight causes
bone mass to be lost. While the response of bone to altered
mechanical states is rapid, it is also occurs in a highly localized
fashion (e.g., tennis player have bigger bones in playing vs
non-playing arms). Additionally, bone response to mechanical
stimuli is focal even within a given bone and appears to occur,
paradoxically, at sites of minimal strain magnitude. In exploring
this phenomenon, we developed poroelasticity based analytical models of
load induced fluid movement within bone. We observed that
specific components of fluid flows induced by the bending of long bones
co-related with localized sites of bone formation that occurred near
minimal strain magnitude sites. As well, we observed in our model
that fluid flows and related bone cell stimulation were dramatically
reduced between the first and subsequent load cycles of a repetitive
exercise-like protocol. Based on these analytical findings, we
hypothesized that inserting an unloaded rest interval between load
cycles could enhance fluid flows in bone and thereby response of bone
to mechanical stimuli. In support, we found in in vivo animal
models that simple insertion of rest between load cycles transformed
impotent loading regimens into stimuli capable of substantially
enhancing bone responses. These results have attractive potential
for application and these experiments exemplify the approach of our
laboratory where we develop mathematical/ analytical models to
understand biological phenomena, utilize the models to develop novel
hypotheses, and in-turn test and validate our hypotheses in vivo.
The ultimate goal of our combined analytical/experimental approach is
to design exercise based interventions for bone loss pathologies and
skeletal fractures that affect a large segment of the elderly
population.