Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy

Abstract

Background: Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy.

Study design: Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored.

Results: Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration.

Conclusions: Administration of oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.

Trial registration: ClinicalTrials.gov NCT00675714.

Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1

Consort diagram.

FIGURE 2

Effect of oxandrolone on percent predicted resting energy expenditure. Data are represented the loess-smoothed trend in resting energy expenditure (REE) with shading indicating +/− standard error. Hatch marks across the bottom represent the density of sampled data at each time point (1,427 total observations). Time points at which differences are significant are indicated with wider lines (p

FIGURE 3

Percent change in height percentile from 1 to 5 years post burn in (A) all patients and in (B) patients aged 7–18 years. Data are expressed as mean ± SEM. *p

FIGURE 4

Percent change in (A) total body bone mineral content and (B) lean body mass. Data are represented as the loess-smoothed trend in BMC and in LBM with shading indicating +/− standard error. Hatch marks across the bottom represent the density of the sampled data at each time point (572 total observations). Time points at which differences are significant are indicated with wider lines (p

FIGURE 5. Exercise

Combined effect of oxandrolone and exercise on percent change in (A) total lean body mass and (B) muscle strength. In (A), data are represented by the loess-smoothed trend in LBM with shading indicating +/− standard error. Hatch marks across the bottom represent the density of the sampled data at each time point (279 total observations). Time points at which differences are significant are indicated with wider lines (p

FIGURE 6

Effect of oxandrolone on serum levels of (A) free T4, (B) free thyroid index, (C) T3 uptake, (D) total T4, (E) IGF-1, (F) IGFBP-3, (G) growth hormone, (H) haptoglobin, (I) C3 complement, (J) retinol-binding protein, (K) α1 acid glycoprotein, (L) transferrin, (M) pre-albumin, (N) estradiol, (O) testosterone, (P) osteocalcin, and (Q) intact parathyroid hormone. Data are expressed as mean±SEM. *p

FIGURE 7

Effect of oxandrolone on levels of (A) serum creatinine, (B) BUN, (C) alkaline phosphatase, (D) total protein, (E) total bilirubin, (F) aspartate aminotransferase, (G) alanine aminotransferase, (H) albumin, and (I) glucose. Data are expressed as mean±SEM. *p