EARLY DIAGNOSIS AND INTERVENTION STRATEGIES FOR POST-TRAUMATIC HETEROTOPIC OSSIFICATION IN SEVERELY INJURED EXTREMITIES

Background: Heterotopic ossification (HO) is a frequent complication in severely traumatized limbs that has a profound effect in slowing and limiting recovery among those affected. In the recent conflicts in Iraq and Afghanistan, HO has occurred in 64%-66% of patients treated for traumatic amputations and in up to 62% of patients treated with limb-sparing procedures.This proposal addresses the critical need for effective methods for early determination of whether and where HO is developing so that effective intervention can be initiated.Hypothesis or Objective: Our objective is to define clinical metrics (analysis of local cells, wound fluid, histology, and biochemistry) can be used alone or in combination to make accurate predictions regarding where and in whom HO will and will not form so that this information can be used to target effective methods of local treatment that can prevent or mitigate HO and to assess the several local therapies.Specific Aims: (1) Characterize the heterogeneity and evolution of the biological environment in exposed tissue sites in wounded warriors under treatment for traumatic amputations of the lower extremity between week 1 and week 4 following injury using multiple modalities: (1-18 months). (2) Develop a predictive model based on a minimum set of clinical variables collected in Aim 1 that will provide clinically useful prediction of where and in whom HO will form. (Target expectation: False positive rate