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

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: janglen{at}iupui.edu
⁴ Comparative Orthopaedic Laboratory, University of Missouri—Columbia, 379 East Campus Drive, Columbia, MO 65211

Investigation performed at the Comparative Orthopaedic Laboratory, Department of Orthopaedics, University of Missouri, Columbia, Missouri

In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from the Orthopaedic Trauma Association. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

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.

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