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.