Metabolic and hormonal changes of severely burned children receiving long-term oxandrolone treatment

Abstract

Objective: When given to children for 1 year after a severe burn, oxandrolone significantly improves lean body mass, bone mineral content, and muscle strength. The beneficial effects of oxandrolone on height and weight were observed 1 year after treatment was discontinued. To study the efficacy of oxandrolone in severely burned children for 12 months after burn and 12 months after the drug was discontinued.

Summary background data: Oxandrolone attenuates body catabolism during the acute phase after burn. It is unclear whether oxandrolone would have any beneficial effects during long-term treatment or if there were any effects after the drug was stopped.

Methods: Sixty-one children with 40% total body surface area burns were enrolled in this study. Patients were randomized into those to receive oxandrolone (n = 30) or placebo (n = 31) for the first 12 months. Treatment was discontinued after 12 months, and the patients were studied without the drug for the following 12 months. At discharge and 6, 12, 18, and 24 months after burn, height, weight, body composition, resting energy expenditure, muscle strength, and serum human growth hormone, insulin-like growth factor-I (IGF-1), IGF binding protein-3, insulin, cortisol, parathyroid hormone, tri-iodothyronine uptake (T3 uptake), and free thyroxine index (FTI) were measured. Statistical analysis used Tukey multiple comparison test. Significance was accepted at P < 0.05.

Results: Oxandrolone improved lean body mass, bone mineral content and muscle strength compared with controls during treatment, P < 0.05. Serum IGF-1, T3 uptake, and FTI were significantly higher during drug treatment compared with controls, P < 0.05. Significant increases in height and weight with oxandrolone were observed after the end of treatment.

Conclusions: Oxandrolone improved body composition and strength in severely burned children during the 12 months of treatment. Its effect on height and weight continued after treatment was discontinued.

FIGURE 1. Schematic of study protocol for Dexa, height and weight, serum (hormone analysis), and clinical assessment (CA) measures. Clinical assessments include physical examinations and screening for adverse side effects, which are evaluated by a committee of 5 clinical experts to decide whether the treatment should be discontinued.

FIGURE 2. Percent change with time in the number of burned children in the greater than 25th percentile/total for height when compared with values obtained at hospital discharge. *Significant changes in height were observed 6–12 months after oxandrolone was discontinued, P < 0.05.

FIGURE 3. Percent change with time in the number of burned children in the greater than 25th percentile/total for weight when compared with values obtained at hospital discharge. *Significant changes in weight were observed 12 months after oxandrolone was discontinued, P < 0.05.

FIGURE 4. Percent change in lean body mass from discharge to 24 months after burn. Values are means ± SEM. *Significant difference between oxandrolone and placebo, P < 0.05.

FIGURE 5. Percent change in bone mineral content when measured by Dual Energy x-ray analysis. Values are mean ± SEM. *Significant difference between oxandrolone and placebo, P < 0.05.

FIGURE 6. Serum concentrations of insulin-like growth factor-1 with time after burn. Values are mean ± SEM. *Significant difference between oxandrolone and placebo, P < 0.05.

FIGURE 7. Effects of oxandrolone on percent uptake of tri-iodothyronine (T3 uptake) with time. Values are mean ± SEM. *Significant difference in T3 uptake between oxandrolone and placebo at 6 months after burn, P < 0.05.

FIGURE 8. Muscle strength was significantly improved with oxandrolone 12 months after burn. Normal values for healthy children: 182 Nm/kg body weight (SD 40). Data are presented as mean ± SEM. *Significant difference between oxandrolone and placebo at P < 0.05.