Improved net protein balance, lean mass, and gene expression changes with oxandrolone treatment in the severely burned

Abstract

Objective: To determine the effects of the anabolic agent oxandrolone on muscle protein and gene expression in severely burned children.

Summary background data: The authors previously showed that oxandrolone increased net muscle protein synthesis in emaciated burned patients receiving delayed treatment for severe burns. They hypothesized that similar effects would be seen in those treated early after burn.

Methods: Thirty-two severely burned children were enrolled in a prospective randomized trial. Subjects underwent studies to assess leg protein net balance 5 days after the first excision and grafting procedure. Immediately after these studies, treatment with placebo (n = 18) or 0.1 mg/kg oxandrolone (n = 14) twice a day was started. One week after this, another net balance study was performed in each subject. Body weights and total body potassium counting were used to determine body compositional changes. Muscle biopsies were taken 1 week after treatment in oxandrolone subjects to examine gene expression changes with gene array (12,600 genes).

Results: Protein net balance did not change in the placebo group, while oxandrolone-treated subjects had a significant improvement. Body weights and fat free mass significantly decreased in the placebo group, while no changes were found in the oxandrolone-treated subjects. Expression changes were seen in 14 genes in the oxandrolone group compared to placebo. Some of these included myosin light chain (+2.7-fold change), tubulin (+2.3), calmodulin (-2.3), and protein phosphatase I inhibitor (-2.8).

Conclusions: Oxandrolone improves protein net balance and lean mass in the severely burned. These changes are associated with increased gene expression for functional muscle proteins.

Figure 1. Net balance of d₅-phenylalanine across the leg without and with oxandrolone treatment. Oxandrolone induced a significant improvement in net balance in the treated group (P = .01), while no significant difference was found in the placebo group.