Session VI - Basic Science


Sat, 10/9/04 Basic Science, Paper #31, 9:15 am

The Role of Anabolic Supplementation in Fracture Healing

Peter Kazmier, MD (n); Timothy A. Burd, MD (n); Jeffrey O. Anglen, MD (n); Michael S. Hughes, MD (n);James L. Cook, PhD (n); Keiichi Kuroki (*);
University of Missouri-Columbia, Columbia, Missouri, USA

Purpose: With the escalating incidence of high-speed motor vehicle trauma and a greater percentage of geriatric patients who have poor nutrition and osteoporosis, a safe and effective nutritional strategy to improve fracture healing is needed. In this study, we compared femoral fracture healing in three groups of rats, each placed on a diet with different protein content. The objective of the study was to examine the differences in fracture callus formation among these three groups.

Methods: We studied 100 adult male rats; 10 animals served as controls, receiving a 15% protein diet throughout the study. The remaining 90 rats received a 6% protein diet for 5 weeks to induce a state of protein malnutrition. At 5 weeks, three treatment groups were formed with 30 per group: group A (malnourished diet) received 6% protein, group B (regular diet) received 15% protein, and group C received a diet of 30% anabolic protein. All three diets were isocaloric. The 90 animals underwent femoral intramedullary nailing followed by creation of a closed midshaft fracture. At 2, 4, and 6 weeks after surgery, 10 animals from each group were sacrificed. The quadriceps and femurs were harvested bilaterally. Histomorphometric analysis of undecalcified sections cut from the point of maximal callus diameter was performed. Total bone area (TBA) and relative bone density (RBD) were determined for each femur. Muscle myosin heavy-chain content was quantified by using MHC electrophoresis. Analysis of variance was used to analyze the data.

Results: All contralateral femora (unfractured) had a significantly smaller TBA and significantly greater RBD than all experimental groups (P <0.001, P <0.01). The anabolic group (C) at 6 weeks had significantly greater RBD than the anabolic (C) group at 2 weeks, the regular diet group (B) at 2 weeks, and the malnourished group (A) at 2, 4, and 6 weeks (P <0.05). The malnourished group (A) femora at 2 weeks had significantly less RBD than all other groups (P <0.001). The anabolic group (C) compared with the malnourished (A) group had an RBD 37% higher at 2 weeks, 32% higher at 4 weeks, and 14% higher at 6 weeks. The anabolic group (C) compared with the regular (B) group had an RBD 5% higher at 2 weeks, 5% higher at 4 weeks, and 11% higher at 6 weeks. Myosin heavy-chain content at the 2-week period was higher in the anabolic (C) and regular (B) diet groups when compared with the malnourished group (A) (P = 0.06).

Conclusion: The histomorphometric analysis corresponded well with data from our previous study regarding densitometry and biomechanical testing. These data suggest that anabolic supplementation with high protein and composed of conditionally essential amino acids may augment fracture callus properties by allowing the rats to heal earlier with a smaller, more mature callus. The results of the muscle myosin heavy-chain content suggest that nutrition plays a significant role in muscle healing.

Significance: Identification of pathways to augment skeletal muscle and fracture healing via anabolic oral supplementation may have direct clinical application by mitigating morbidity, specifically nonunion rates, infection, and rehabilitation, as well as mortality in orthopaedic patients. Anabolic protein supplementation may benefit fracture healing.