Skeletal tissues maintain a balance between mechanical wear and tear (i.e. fatigue) damage and intrinsic, matrix-level repair.  Imbalance in this damage-repair homeostasis, either because of
excessively rapid damage accumulation or because of ineffective, inadequate or inappropriate biological responses to chronic injury, leads to pathology and ultimately, mechanical failure of skeletal
elements.  These processes are implicated in a wide range of conditions, including overuse injuries, tissue fragility in aging, tendon and ligament failures and degenerative joint disease.
     A major function of Haversian (osteonal) remodeling is to remove and replace regions of compact bone which accumulate microdamage due to fatigue.  However, little is known about the damage or remodeling
responses which occur at the levels of fatigue expected to result from normal wear and tear.  In particular, how bone remodeling units "target" microscopically damaged areas of bone is unknown.  Our recent
studies of remodeling-repair of microdamage find that intracortical resorption effectively removes both linear-type microcracks and diffuse matrix damage. Alterations of osteocyte and canalicular integrity are
observed in microdamaged areas.  Resorption spaces were also seen within areas of cortex in which no bone matrix damage occurred, but alterations of osteocyte and canalicular integrity were evident.
Recent studies indicate that these alterations of osteocyte integrity correspond to osteocyte apoptosis, or programmed cell death. Thus, osteocyte death or damage may provide a key stimulus for this signaling
or targeting the remodeling process in bone.