Hip fracture and resultant surgical repair entail a significant loss of muscle mass and function. Both injury and surgery, in and of themselves, initiate a cascade of events which lead to the loss of muscle mass. The general premise of this project is that this initial loss of muscle protein during surgery and the accompanying convalescence predispose a generally compromised patient to poor functional or morbidity outcomes. Further, we propose that muscle protein is lost due to a significant alteration in the muscle protein metabolism. The general goal of this project is to investigate interventions designed to ameliorate the negative muscle balance between protein synthesis and protein breakdown. We hypothesize the enhancement of muscle anabolism is required for these patients to recover muscle strength and function. We first propose to restore muscle protein synthesis throughout hospitalization with the administration of an essential am/no acid formula. We further propose that the amelioration of hypercortisolemia after surgery will result in a decreased muscle protein breakdown. The amelioration of hypercortisolemia after surgery will be accomplished with a common antifungal agent, ketoconazole, in order to investigate the resultant affects on muscle protein breakdown. We will measure lean body mass and muscle volume, as well as functional outcomes before surgery and discharge from acute hospitalization to determine the efficancy of these interventions. We will utilize stable isotope methodology to quantify muscle protein metabolism after acute hospitalization. We will also amplify these results by investigating cellular markers of protein breakdown to corroborate our metabolic endpoints.

R01AR052293

2006-09-01

2011-08-31