BONE PAIN AND METABOLIC BONE DISEASE

THIS PROJECT WILL ADDRESS (1) A NEW METHOD FOR EVALUATING THE NUTRITIONAL STATUS OF PATIENTS, (2) THE ADEQUACY OF PARENTERAL NUTRITION THERAPY, (3) NEW FORMULATIONS OF NITROGEN-CONTAINING PARENTERAL NUTRITION FLUIDS, (4) THE ACHIEVEMENT OF REDOX BALANCE WITHIN THE ORGANS TO WHICH THE NEW FORMULATIONS ARE ADMINISTERED, (5) CONTROL OF THE CELLULAR PHOSPHORYLATION STATE DUE TO THE REDOX BALANCE, AND(6) THE RESULTANT IMPROVEMENTS IN THE EFFICIENCY OF FUNCTIONOF THE ORGANS IN QUESTION. THE NEW PARENTERAL NUTRIENT SOLUTIONS WILL AVOID THE TOXIC EFFECTS OF CURRENT ACETATE- CONTAINING PARENTERAL SOLUTIONS. THESE SOLUTIONS, WITH 40- 140 MM ACETATE, CAUSE PATHOLOGICAL ACCUMULATIONS OF CALCIUM,PHOSPHATE, AND INORGANIC PYROPHOSPHATE WITHIN THE LIVER AND OTHER ORGANS. THIS IN TURN RESULTS IN THE CHRONIC BONE PAINAND METABOLIC BONE DISEASE SEEN IN PATIENTS WITH LONG-TERM PARENTERAL NUTRITION. BY REEXAMINING THE COMPONENTS OF PRESENT PARENTERAL NUTRITION FORMULATIONS AND THE RELATION- SHIP OF THE COMPONENT CONCENTRATIONS, PHOSPHO-ENERGETICS HOPES TO ACHIEVE AN OPTIMUM COMPONENT MIXTURE THAT WILL INCREASE ORGAN PROTEIN CONTENT AND/OR INCREASE ORGAN FUNCTIONAL CAPACITY. PRESENT PARENTERAL NUTRITIONAL SUPPLEMENTS IN MALNOURISHED PATIENTS GENERALLY FAIL TO RESTORE EITHER A POSITIVE NITROGEN BALANCE OR A DEMONSTRABLEINCREASE IN FUNCTIONAL CAPACITY WHEN ADMINISTERED OVER A ONE-WEEK PERIOD. IN PHASE II, THE 31 P NMR SPECTRA OF SKELETAL MUSCLES OF PATIENTS RECEIVING PARENTERAL NUTRITION AT REST, DURING EXERCISE, AND DURING RECOVERY WILL BE DETERMINED. MEASUREMENTS OF THE WORK CAPACITY OF THE MUSCLEON CONVENTIONAL TOTAL PARENTERAL NUTRITIONAL SUPPLEMENTS ANDON THE NEWER REDOX-BALANCED NUTRITIONAL SUPPLEMENTS FOR ONE WEEK AND ONE MONTH WILL ALSO BE TAKEN. THE AIM WILL BE TO MAKE ANY SIGNIFICANTLY IMPROVED FORMULATIONS GENERALLY AVAILABLE.