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Improved net protein balance, lean mass, and gene expression changes with oxandrolone treatment in the severely
Steven E Wolf1, Steven J Thomas, Mohan R Dasu
1Department of Surgery, Shriners Burns Hospital, University of Texas Medical Branch, 815 Market, Galveston, TX 77550, USA. swolf@utmb.edu
Insights
Oxandrolone treatment significantly improved muscle protein balance and preserved lean body mass in severely burned children. This anabolic effect was linked to increased gene expression for key muscle proteins.
Area of Science:
- Biochemistry
- Molecular Biology
- Pediatric Medicine
Background:
- Previous studies indicated oxandrolone enhances muscle protein synthesis in burned patients with delayed treatment.
- This study investigated early treatment effects in severely burned children.
Purpose of the Study:
- To evaluate the impact of oxandrolone on muscle protein and gene expression in pediatric burn patients.
- To determine if early oxandrolone administration benefits severely burned children.
Main Methods:
- A prospective randomized trial involving 32 severely burned children.
- Assessment of leg protein net balance, body composition, and gene expression changes via muscle biopsies.
- Treatment with either placebo or oxandrolone (0.1 mg/kg twice daily).
Main Results:
- Oxandrolone significantly improved protein net balance compared to placebo.
- Placebo group experienced decreased body weight and fat-free mass; oxandrolone group showed no significant changes.
- Observed gene expression changes in oxandrolone-treated subjects, including upregulation of myosin light chain and tubulin.
Conclusions:
- Oxandrolone administration is effective in improving protein net balance and maintaining lean mass in severely burned children.
- The observed benefits are associated with enhanced gene expression related to muscle protein synthesis.
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.