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


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.
Gottschalck
Ida B
IB
Sanos Bioscience, Copenhagen, Denmark. ida.g@mail.dk
Jeppesen
Palle B
PB
Holst
Jens J
JJ
Henriksen
Dennis B
DB
D015415:Biomarkers / Q000097:blood; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D003082:Colectomy / Q000009:adverse effects; D024042:Collagen Type I / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007081:Ileostomy / Q000009:adverse effects; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012778:Short Bowel Syndrome / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D016896:Treatment Outcome
D015415:Biomarkers; D024042:Collagen Type I; D053767:Glucagon-Like Peptide 2