Long-term oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury

Abstract

Background: We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated whether oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury.

Methods: At the time of admission, patients were randomized to control or oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover.

Results: Protein kinetics in leg muscle were expressed in nmol/min per 100 mL leg volume (mean ± SE). During AA infusion, rates of protein synthesis in leg muscle were increased (P < .05) in both groups (basal vs AA: control, 51 ± 8 vs 86 ± 21; oxandrolone, 56 ± 7 vs 96 ± 12). In the control group, there was also a simultaneous increase in breakdown (basal vs AA: 65 ± 10 vs 89 ± 25), which resulted in no change in the net balance of leg muscle protein (basal vs AA: -15 ± 4 vs -2 ± 10). In the oxandrolone group, protein breakdown did not change (basal vs AA: 80 ± 12 vs 77 ± 9), leading to increased net balance (basal vs AA: -24 ± 7 vs 19 ± 7; P < .05). Protein breakdown at the whole-body level was not different between the groups.

Conclusion: Long-term oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown.

Figure 1

Stable isotope infusion protocol.

Figure 2

Leg muscle protein kinetics. Data are presented as mean±SE. In both groups, muscle protein synthesis, as represented by rate of disappearance (R_d), was greater following amino acid (AA) infusion than during basal period (A). AA infusion did not affect leg muscle protein breakdown, as represented by rate of appearance (R_a) in either group (B). In the control group, it increased by 36% (p = .19, basal period vs. AA infusion), and in the oxandrolone group, it decreased by 4% (p = .85, basal period vs. AA period infusion). As a result, during AA infusion, the net deposition of muscle protein did not change in the control group but significantly increased in the oxandrolone group (C). *, p < .05, significantly different from basal period.

Figure 3

Whole-body endogenous phenylalanine kinetics. Data are presented as mean±SE. A, Rate of appearance (R_a) of whole-body protein (which is a reflection of protein breakdown). In the oxandrolone group, whole-body protein R_a was significantly (p < .05) lower following AA infusion than during basal period. B, Whole-body muscle protein R_a. C, whole-body non-muscle protein R_a. AA infusion did not affect whole-body muscle R_a (B) or whole-body non-muscle protein R_a in either group (C). *, p < .05, significantly different from basal period.