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Enhanced Fracture and Soft-Tissue Healing by Means of Anabolic Dietary Supplementation

Hughes, Michael S. MD; Kazmier, Peter MD; Burd, Timothy A. MD; Anglen, Jeff MD; Stoker, Aaron M. PhD; Kuroki, Keiichi DVM, PhD; Carson, William L. PhD; Cook, James L. DVM, PhD

Journal of Bone & Joint Surgery - American Volume: November 2006 - Volume 88 - Issue 11 - p 2386–2394
doi: 10.2106/JBJS.F.00507
Scientific Articles

Background: Malnutrition is common in hospitalized injured patients. It contributes to delayed fracture-healing and increased morbidity. However, relatively little attention has been directed toward nutritional strategies for augmenting musculoskeletal recovery after a fracture. This animal study was designed to examine the effects of dietary protein intake and the role of conditionally essential amino acids in muscle and bone-healing after a fracture.

Methods: One hundred adult male rats were used. Ten rats served as controls and received a 15% protein diet throughout the study. The remaining ninety rats received a 6% protein diet for five weeks to induce protein malnutrition. The rats underwent intramedullary nailing and closed midshaft fracture of one femur. After the fracture, they were separated into three isocaloric dietary groups. Group P6 received a diet with 6% protein; Group P15, a diet with 15% protein; and group P30, a diet with 30% protein with conditionally essential amino acids. At two, four, and six weeks after surgery, ten animals from each group were killed and the femora were evaluated with dual x-ray absorptiometry, histomorphometric assessment of callus, and torsional testing. The quadriceps muscles were analyzed for total mass, total protein content, and for mRNA expression of insulin-like growth factor-1 (IGF-1), IGF-2, IGF receptors, actin, myosin, and vascular endothelial growth factor (VEGF).

Results: The P30 group demonstrated elevations in albumin, body mass, muscle mass, total protein content of muscle, and bone mineral density in the fracture callus compared with the P6 diet group at six weeks (p < 0.05). Molecular analysis of muscle revealed that IGF-1, IGF-2, IGF receptors, myosin, actin, and VEGF gene expression were significantly (p < 0.001) higher in the P6 group compared with the P30 group. Biomechanical testing of the femora, however, showed no significant differences.

Conclusions: Dietary supplementation with conditionally essential amino acids in malnourished animals had anabolic effects on bone mineralization, body mass, and muscle mass.

Clinical Relevance: Identifying methods for augmenting skeletal muscle and fracture-healing by means of oral protein supplementation may provide cost-effective, direct clinical benefits to orthopaedic patients.

1 Department of Orthopaedics, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65212

2 Nebraska Spine Center, 11819 Miracle Hills Drive, Suite 102, Omaha, NE 68154

3 Department of Orthopaedics, Indiana University, 541 Clinical Drive, Suite 600, Indianapolis, IN 46202. E-mail address:

4 Comparative Orthopaedic Laboratory, University of Missouri—Columbia, 379 East Campus Drive, Columbia, MO 65211

Copyright 2006 by The Journal of Bone and Joint Surgery, Incorporated
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