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).


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.
Gottschalck
Ida B
IB
Sanos Bioscience, Copenhagen, Denmark. ida.g@mail.dk
Jeppesen
Palle B
PB
Hartmann
Bolette
B
Holst
Jens J
JJ
Henriksen
Dennis B
DB
D000328:Adult; D015992:Body Mass Index; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology; D002940:Circadian Rhythm; D003082:Colectomy; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage*; D006801:Humans; D007081:Ileostomy; D007279:Injections, Subcutaneous; D007582:Jejunostomy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D012778:Short Bowel Syndrome / Q000150:complications / Q000503:physiopathology*; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D053767:Glucagon-Like Peptide 2; D010281:Parathyroid Hormone