Pamidronate attenuates muscle loss after pediatric burn injury

Abstract

Children who are burned >40% total body surface area lose significant quantities of both bone and muscle mass because of acute bone resorption, inflammation, and endogenous glucocorticoid production, which result in negative nitrogen balance. Because administration of the bisphosphonate pamidronate within 10 days of the burn injury completely prevents the bone loss, we asked whether muscle protein balance was altered by the preservation of bone. We reviewed the results from 17 burned pediatric subjects previously enrolled in a double-blind randomized controlled study of pamidronate in the prevention of post-burn bone loss and who were concurrently evaluated for muscle protein synthesis and breakdown by stable isotope infusion studies during the acute hospitalization. We found a significantly lower fractional protein synthesis rate (FSR) in the pamidronate group and a correspondingly lower rate of appearance of the amino acid tracer in venous blood, suggesting lower muscle protein turnover. Moreover, net protein balance (synthesis minus breakdown) was positive in the subjects receiving pamidronate and negative in those receiving placebo. Muscle fiber diameter was significantly greater in the pamidronate subjects and leg strength at 9 months post-burn was not different between subjects who received pamidronate and normal physically fit age-matched children studied in our lab. Leg strength in burned subjects who served as controls tended to be weaker, although not significantly so. If substantiated by a larger study, these results suggest that bone may have a paracrine mechanism to preserve muscle and this finding may have implications for the treatment of sarcopenia in the elderly.

Keywords: BONE AND MUSCLE LOSS; BURN INJURY; PAMIDRONATE.

© 2014 American Society for Bone and Mineral Research.

Figures

1

Fractional synthetic rate (FSR) of muscle protein during a basal period (FSR 1) and during an unlabelled amino acid infusion period (FSR2) in pamidronate and control subjects. Results are expressed as percent per hour.

2

Rate of appearance (Ra) of phenylalanine in venous blood in pamidronate and control subjects expressed as nmol/min/100 ml leg volume.

3

Net balance (NB, synthesis minus breakdown) of phenylalanine as calculated from the arterio-venous difference in phenylalanine concentration multiplied by the blood flow and expressed as nmol/min/100 ml leg volume.

4

Muscle fiber diameter from m. vastus lateralis biopsies of subjects receiving either pamidronate or placebo and expressed in microns.