Essential Amino Acid Supplementation for Femoral Fragility Fractures

This trial will evaluate the impact of 6 weeks of postoperative essential amino acid (EAA)-based supplementation on muscle morphology after femoral fragility fracture. This trial will assess the ability of EAA-based to increase skeletal muscle metabolic activity, reduce inflammation, and induce muscle fiber hypertrophy, as well as preserve skeletal muscle mass and physical performance up to 3 months after injury. Participants will be randomized in a 1:1 ratio to 1) standard of care (no dietary intervention) or 2) EAA-based supplementation

This study consists of 5 study visits that occur over 12 weeks after operative fixation of femoral fragility fracture. Consenting participants will be asked to complete the study assessments/procedures at the time points described below. Patients will be treated with operative fixation of their fracture per standard of care. Day of Surgery (DOS) Visit: Mini-Mental State Examination (MMSE-2®): This is a screening tool for cognitive impairment and will be used to determine eligibility for the study. Subjects will be randomized to the intervention arm or control arm in a 1:1 ratio. Subjects randomized to the control arm will receive standard of care nutrition during hospital admission. Subjects randomized to intervention arm of this study will receive essential amino acid (EAA)-based oral nutrition supplementation in addition to standard of care nutrition. Subjects will take the supplement twice daily for 6 weeks after injury. Supplementation will begin within 72 hours of hospital admission. Muscle Biopsy: Biopsies will be obtained from the superficial vastus lateralis muscle on the injury extremity. Biopsies will be performed by board-certified orthopedic surgeons. Systemic Inflammatory Labs: A sample of about 15 mL of peripheral venous blood will obtained by trained clinical staff. Postoperative Day 1 (POD1) Visit: Body composition: Will be assessed using a bioelectrical impedance analysis (BIA) device (InBody S10 Body Composition Analyzer). This is non-invasive test that uses a low-level imperceptible electrical current to measure body composition and body water. In a supine position, electrodes are placed on the hands and ankles of the subjects and the result is recorded in the BIA device. This assessment will be performed by trained study team members. Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function: This is a survey that asks subjects to report on subjective measures of pain and physical function. This survey is a computer adaptive test that is completed in REDCap® using a tablet or computer. Subjects will self-administer this survey 2-Week Clinic Visit: Muscle biopsy Systemic inflammatory labs 6-seek Clinic Visit: Systemic inflammatory labs Body composition PROMIS Physical Function 12-week Clinic Visit: Body composition PROMIS Physical Function Physical Performance Measures: Objective measures of physical performance (mobility, strength, power, & balance) will be assessed with the Short Physical Performance Battery (SPPB)14 and the Timed Up & Go (TUG)15 test. During the SPPB, subjects will complete the following physical assessments - ability to stand for 10 seconds with feet in 3 different positions (together side-by-die, semi-tandem, & tandem), two timed trials of a 4-meter walk, and time to rise from a chair 5 times. During the TUG, subjects will complete the following physical assessment - time to rise from a chair, walk 3 meters, return, & sit down. This assessment will be performed by trained study team members.

Subjects randomized to intervention arm of this study will receive essential amino acid (EAA)-based oral nutrition supplementation in addition to standard of care postoperative nutrition. Subjects will take 1 scoop (26.7g) of supplement twice daily for 6 weeks after injury. Supplementation will begin within 72 hours of hospital admission. The EAA-based supplement used in this clinical trial is MEND™ Repair and Recover®.

Subjects randomized to the control arm of this study will receive no intervention. They will receive standard of care postoperative nutrition.

Powdered supplement that can be mixed into beverage of choice. Ingredients: Zinc, Vitamin A, Vitamin C, Whey Protein, Leucine, Calcium, Vitamin D, Glutamine, Boron, Turmeric, Bioperine, Iron, β-hydroxy β-methylbutyrate (HMB)

Biopsy results will provide the muscle physiology information of satellite cell counts per mm2 (SC/mm2)

Biopsy results will provide the muscle physiology information of myonuclei density by examining the myonuclei domains per µm2 (myonuclei domains, e.g., smaller number of myonuclei domains indicates higher myonuclei density) counting the myonuclear number per fiber

Biopsy results will provide the muscle physiology information for the type 1 and 2 muscle fiber cross sectional area in µm2.

The following metrics will be used to characterize muscle physiology through serum analysis: levels of myostatin, c-terminal agrin fragment, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α).

Physical performance will be measured objectively via the Short Physical Performance Battery (SPPB) & Timed Up & Go (TUG). Patient-reported physical performance will be measured using the PROMIS-Physical Function survey.

Inclusion Criteria: Hospital inpatient Age ≥ 65 years old on admission Low-energy mechanism of injury Diagnosis of femur fracture (OTA 31, 32, or 33 fracture) Indicated for surgical fixation Able to provide informed consent Exclusion Criteria: Part of a vulnerable population (ex: Incarcerated, Non-English speaking) Cognitive impairment (MMSE score ≤ 17) Electrical medical implant (ex: Pacemaker/Defibrillator, Left Ventricular Assist Device, Cochlear implant, Insulin pump, Pain medication pumps, Spinal cord stimulator) Non-ambulatory prior to injury Inability to consume an oral diet or allergy to supplement ingredients (ex: milk allergy) Concern for inability to complete follow-up