|Burrin, Douglas - Doug|
Submitted to: Pediatric Research
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2005
Publication Date: 5/1/2005
Citation: Horst, D.A., Sedenquist, M., Stoll, B., Burrin, D.G. 2005. Glucagon-like peptide 2 decreases a marker of bone resorption in tpn-fed neonatal piglets [abstract]. Pediatric Academic Society Meeting. Pediatric Research. 57:Abstract 1609. 2005 CDROM. Interpretive Summary: Interpretive Summary not needed for this 115.
Technical Abstract: BACKGROUND: Maintaining adequate bone mineralization in premature infants is a major challenge, especially during total parenteral nutrition (TPN). Glucagon-like peptide 2 (GLP-2), a nutrient-responsive, intestinotrophic gut hormone that regulates neonatal intestinal function, decreases bone resorption and increases bone mineral density in adult women and patients with short-bowel syndrome. The effects of GLP-2 on bone mineralization in newborns are unknown. OBJECTIVE: To test the hypothesis that GLP-2 decreases bone resorption independent of intestinal calcium absorption in neonatal piglets. DESIGN/METHODS: Three-day old piglets were implanted with jugular venous and carotid arterial catheters and given a nutritionally complete TPN solution for seven days. Piglets were randomized to receive a continuous intravenous infusion of either GLP-2 (15 microgram/kg/d; n=5) or saline (n=5). Arterial blood was sampled at 0, 6, 12, 24, 48, 72, 120 and 168 hours after beginning treatment. Serum concentrations of osteocalcin and degradation fragments of the C-terminal telopeptide region of collagen type I (s-CTX) were assayed as markers of bone formation and resorption, respectively. Expression of GLP-2 receptor RNA in bone was assessed using QRT-PCR. RESULTS: In control piglets, serum s-CTX and s-osteocalcin increased significantly during the seven-day period. Expressed as a percent of the time zero (baseline=100%), the mean serum s-CTX was significantly higher in control than in GLP-2 treated pigs (128.5 +/- 4.8 vs 108.3 +/- 4.7; P=0.004). Mean percent changes from time zero for s-osteocalcin in control and GLP-2 treated pigs were not different (183.4 +/- 12.4 vs 183.8 +/- 12.6; P=0.98). GLP-2 receptor mRNA was abundant in small intestine and stomach, but undetectable in bone. CONCLUSIONS: In TPN-fed neonatal piglets, GLP-2 treatment significantly decreased markers of bone resorption, but not formation. The absence of GLP-2R mRNA in bone suggests that GLP-2 may indirectly enhance bone mineralization in neonates and provide a new therapeutic option for treatment of osteopenia in premature or TPN-dependent infants.