Reduction in bone resorption by exogenous glucagon-like peptide-2 administration requires an intact gastrointestinal tract

Scand J Gastroenterol. 2008 Aug;43(8):929-37. doi: 10.1080/00365520801965381.

Abstract

Objective: Biochemical markers for bone resorption (s-CTX) are reduced by food intake, whereas markers for bone formation seem to be unaffected by meal status. Glucagon-like peptide-2 (GLP-2) is a peptide secreted from endocrine L cells in the intestinal mucosa in relation to food-intake. Subcutaneous GLP-2 treatment has been shown to reduce bone resorption in postmenopausal women. The objective of this study was to investigate the ability of exogenous GLP-2 to reduce bone resorption in patients with jejunostomy or ileostomy and to elucidate whether an intact gastrointestinal tract and the ability to secrete GLP-2 are required for meal-induced inhibition of bone resorption.

Material and methods: Fifteen control subjects, 13 colectomized patients with an ileostomy and 12 colectomized patients with a jejunostomy (remnant small bowel 89 +/- 53 cm) were given: a) a subcutaneous injection of 1600 microg GLP-2, b) placebo and c) 3.8 MJ of a breakfast meal. Blood was sampled for measurements of s-CTX, s-osteocalcin and GLP-2 for 4 h after each intervention.

Results: After the GLP-2 injection, only control subjects showed a significant reduction in s-CTX (24% +/- 13%, p = 0.05, 120 min) compared with baseline values. Patients with an ileostomy had a preserved endogenous postprandial GLP-2 secretion, which was absent in patients with a jejunostomy. Consumption of a meal reduced s-CTX in all groups but significantly less so in the jejunostomy group.

Conclusions: Reductions in bone resorption by exogenous GLP-2 require an intact gastrointestinal tract. The decreased meal-induced inhibition of bone resorption in the jejunostomy patients, who lack a GLP-2 response, supports the view that GLP-2 plays a role in postprandial reduction in bone resorption.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers / blood
  • Bone Resorption / blood
  • Bone Resorption / drug therapy*
  • Bone Resorption / etiology
  • Colectomy / adverse effects
  • Collagen Type I / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide 2 / administration & dosage*
  • Glucagon-Like Peptide 2 / pharmacokinetics
  • Humans
  • Ileostomy / adverse effects
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Radioimmunoassay
  • Retrospective Studies
  • Short Bowel Syndrome / blood
  • Short Bowel Syndrome / complications*
  • Short Bowel Syndrome / drug therapy
  • Treatment Outcome

Substances

  • Biomarkers
  • Collagen Type I
  • Glucagon-Like Peptide 2