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. 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.

Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome.

OBJECTIVE: The gut hormone GLP-2 (glucagon-like peptide-2) seems to be involved in the circadian pattern of bone resorption, whereas parathyroid hormone (PTH) is an established key hormone in bone turnover. Endogenous GLP-2 secretion is lacking in colectomized patients with short-bowel syndrome (SBS) and they have reduced bone mineral density (BMD). The aim of the study was to investigate the anti-resorptive effect (assessed by s-CTX) of 14 days of GLP-2 treatment in these patients and to determine whether 56 days of treatment would improve BMD. PTH secretion in response to GLP-2 was also investigated in colectomized SBS patients and colectomized controls (with ileostomy). MATERIAL AND METHODS: Eight SBS patients and 13 patients with ileostomy were treated with subcutaneous injections of 1600 microg GLP-2 at bedtime for 56 and 14 consecutive days, respectively. BMD was determined at days 1 and 56 in SBS patients. On days 1 and 14, measurements of CTX, P1NP and PTH were taken 4 h after the GLP-2 injection. RESULTS: Patients with ileostomy showed a significant reduction in bone resorption after GLP-2 injections at days 1 and 14. In contrast, there was no change in s-CTX after 1 and 14 days in the SBS patients, and after 56 days of GLP-2 treatment there was no improvement in BMD. A significant reduction in PTH secretion in response to GLP-2 was observed only in patients with ileostomy. CONCLUSIONS: The decreased bone resorption in response to GLP-2 injections cannot be elicited in SBS patients and therefore precludes treatment of their osteopenia with GLP-2. The anti-resorptive response to GLP-2 seems to require an intact small intestine and may involve suppression of PTH secretion.

Bone resorption is decreased postprandially by intestinal factors and glucagon-like peptide-2 is a possible candidate.

OBJECTIVE: Food intake inhibits bone resorption by a mechanism thought to involve gut hormones, and the intestinotrophic glucagon-like peptide 2 (GLP-2) is a candidate because exogenous GLP-2 inhibits bone resorption in humans. The purpose of the study was to investigate patients with short-bowel syndrome (SBS) or total gastrectomy in order to elucidate whether the signal for the meal-induced reduction of bone resorption is initiated from the stomach or the intestine. MATERIAL AND METHODS: Bone resorption was assessed from the serum concentration of collagen type I C-telopeptide cross-links (s-CTX) and compared with the plasma concentrations of GLP-2. Bone formation was assessed from serum osteocalcin concentrations. Seven SBS patients with a preserved colon and 7 with SBS and colectomy and 7 healthy controls were given a breakfast test meal (936 kcal). Eight patients who had undergone total gastrectomy had an oral glucose load (75 g in 150 ml). RESULTS: The SBS patients without a colon showed no reduction in bone resorption (s-CTX) to a meal, whereas SBS patients with a colon had an intermediate response with a 27% (p<0.05) reduction of s-CTX from baseline after 120 min as compared with 66% (p<0.001) for normal controls. A significant reduction of 53% (p<0.001) was seen in gastrectomized patients after receiving oral glucose, which is comparable with the published data for the oral glucose tolerance test (OGGT) in healthy subjects (50% reduction over 120 min). Bone formation was unchanged for both SBS and gastrectomy patients. GLP-2 concentrations increased significantly in all groups with the exception of the SBS plus colectomy group. CONCLUSIONS: An intestinal factor is responsible for the postprandial reduction in bone resorption, and our findings are compatible with such a function for GLP-2.