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GLP-2 and GIP exert separate effects on bone turnover: A randomized, placebo-controlled, crossover study in healthy young men

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Skov-Jeppesen, Kirsa ; Svane, Maria S ; Martinussen, Christoffer ; Gabe, Maria B N ; Gasbjerg, Lærke Smidt ; Veedfald, Simon ; Bojsen-Møller, Kirstine N ; Madsbad, Sten ; Holst, Jens J ; Rosenkilde, Mette M ; Hartmann, Bolette. / GLP-2 and GIP exert separate effects on bone turnover : A randomized, placebo-controlled, crossover study in healthy young men. I: Bone. 2019 ; Bind 125. s. 178-185.

Bibtex

@article{74701b74e9c24fa3aa740602c960ece4,
title = "GLP-2 and GIP exert separate effects on bone turnover: A randomized, placebo-controlled, crossover study in healthy young men",
abstract = "BACKGROUND: Glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) both inhibit bone resorption in humans but the underlying mechanisms are poorly understood. In vitro, GLP-2 activates the GIP-receptor (GIPR).OBJECTIVE: Based on in vitro studies, we hypothesized that the antiresorptive effect of GLP-2 was mediated through the GIPR. This was tested using the selective GIPR-antagonist GIP(3-30)NH2.METHODS: The study was a randomized, single-blinded, placebo-controlled, crossover study conducted at Hvidovre University Hospital, Denmark. Eight healthy young men were included and studied on four study days: GIP (200 μg), GLP-2 (800 μg), GIP(3-30)NH2 (800 pmol/kg/min) + GLP-2 (800 μg), and placebo. The main outcomes were bone resorption measured as collagen type 1 C-terminal telopeptide (CTX) and bone formation measured as procollagen type 1 N-terminal propeptide (P1NP).RESULTS: CTX (mean ± SEM) significantly decreased after both GIP (to 55.3 ± 6.3{\%} of baseline at t = 90 min) and GLP-2 (to 60.5 ± 5.0{\%} of baseline at t = 180 min). The maximal reduction in CTX after GIP(3-30)NH2 + GLP-2 (to 63.2 ± 3.1{\%} of baseline) did not differ from GLP-2 alone (p = 0.95) nor did net AUC0-240 (-6801 ± 879{\%}*min vs -6027 ± 648{\%}*min, p = 0.56). At t = 30 min, GIP significantly (p < 0.0001) increased P1NP to 115.1 ± 2.2{\%} of baseline compared with 103.1 ± 1.5{\%} after placebo. Both GLP-2 and GIP(3-30)NH2 + GLP-2 significantly (p < 0.0001) decreased P1NP to 91.3 ± 1.1{\%} and 88.1 ± 3.0{\%} of baseline, respectively (at t = 45 min) compared with placebo.CONCLUSIONS: GIPR antagonism did not inhibit the GLP-2-induced reduction in bone resorption (CTX) in healthy young men. In contrast to GLP-2, GIP increased P1NP despite decreasing CTX indicating an uncoupling of bone resorption from formation. Thus, GLP-2 and GIP seem to exert separate effects on bone turnover in humans.CLINICAL TRIALS INFORMATION: ClinicalTrials.gov (NCT03159741).",
keywords = "Bone formation, Bone resorption, CTX, P1NP, PTH",
author = "Kirsa Skov-Jeppesen and Svane, {Maria S} and Christoffer Martinussen and Gabe, {Maria B N} and Gasbjerg, {L{\ae}rke Smidt} and Simon Veedfald and Bojsen-M{\o}ller, {Kirstine N} and Sten Madsbad and Holst, {Jens J} and Rosenkilde, {Mette M} and Bolette Hartmann",
note = "Copyright {\circledC} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = "8",
doi = "10.1016/j.bone.2019.05.014",
language = "English",
volume = "125",
pages = "178--185",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc",

}

RIS

TY - JOUR

T1 - GLP-2 and GIP exert separate effects on bone turnover

T2 - A randomized, placebo-controlled, crossover study in healthy young men

AU - Skov-Jeppesen, Kirsa

AU - Svane, Maria S

AU - Martinussen, Christoffer

AU - Gabe, Maria B N

AU - Gasbjerg, Lærke Smidt

AU - Veedfald, Simon

AU - Bojsen-Møller, Kirstine N

AU - Madsbad, Sten

AU - Holst, Jens J

AU - Rosenkilde, Mette M

AU - Hartmann, Bolette

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/8

Y1 - 2019/8

N2 - BACKGROUND: Glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) both inhibit bone resorption in humans but the underlying mechanisms are poorly understood. In vitro, GLP-2 activates the GIP-receptor (GIPR).OBJECTIVE: Based on in vitro studies, we hypothesized that the antiresorptive effect of GLP-2 was mediated through the GIPR. This was tested using the selective GIPR-antagonist GIP(3-30)NH2.METHODS: The study was a randomized, single-blinded, placebo-controlled, crossover study conducted at Hvidovre University Hospital, Denmark. Eight healthy young men were included and studied on four study days: GIP (200 μg), GLP-2 (800 μg), GIP(3-30)NH2 (800 pmol/kg/min) + GLP-2 (800 μg), and placebo. The main outcomes were bone resorption measured as collagen type 1 C-terminal telopeptide (CTX) and bone formation measured as procollagen type 1 N-terminal propeptide (P1NP).RESULTS: CTX (mean ± SEM) significantly decreased after both GIP (to 55.3 ± 6.3% of baseline at t = 90 min) and GLP-2 (to 60.5 ± 5.0% of baseline at t = 180 min). The maximal reduction in CTX after GIP(3-30)NH2 + GLP-2 (to 63.2 ± 3.1% of baseline) did not differ from GLP-2 alone (p = 0.95) nor did net AUC0-240 (-6801 ± 879%*min vs -6027 ± 648%*min, p = 0.56). At t = 30 min, GIP significantly (p < 0.0001) increased P1NP to 115.1 ± 2.2% of baseline compared with 103.1 ± 1.5% after placebo. Both GLP-2 and GIP(3-30)NH2 + GLP-2 significantly (p < 0.0001) decreased P1NP to 91.3 ± 1.1% and 88.1 ± 3.0% of baseline, respectively (at t = 45 min) compared with placebo.CONCLUSIONS: GIPR antagonism did not inhibit the GLP-2-induced reduction in bone resorption (CTX) in healthy young men. In contrast to GLP-2, GIP increased P1NP despite decreasing CTX indicating an uncoupling of bone resorption from formation. Thus, GLP-2 and GIP seem to exert separate effects on bone turnover in humans.CLINICAL TRIALS INFORMATION: ClinicalTrials.gov (NCT03159741).

AB - BACKGROUND: Glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) both inhibit bone resorption in humans but the underlying mechanisms are poorly understood. In vitro, GLP-2 activates the GIP-receptor (GIPR).OBJECTIVE: Based on in vitro studies, we hypothesized that the antiresorptive effect of GLP-2 was mediated through the GIPR. This was tested using the selective GIPR-antagonist GIP(3-30)NH2.METHODS: The study was a randomized, single-blinded, placebo-controlled, crossover study conducted at Hvidovre University Hospital, Denmark. Eight healthy young men were included and studied on four study days: GIP (200 μg), GLP-2 (800 μg), GIP(3-30)NH2 (800 pmol/kg/min) + GLP-2 (800 μg), and placebo. The main outcomes were bone resorption measured as collagen type 1 C-terminal telopeptide (CTX) and bone formation measured as procollagen type 1 N-terminal propeptide (P1NP).RESULTS: CTX (mean ± SEM) significantly decreased after both GIP (to 55.3 ± 6.3% of baseline at t = 90 min) and GLP-2 (to 60.5 ± 5.0% of baseline at t = 180 min). The maximal reduction in CTX after GIP(3-30)NH2 + GLP-2 (to 63.2 ± 3.1% of baseline) did not differ from GLP-2 alone (p = 0.95) nor did net AUC0-240 (-6801 ± 879%*min vs -6027 ± 648%*min, p = 0.56). At t = 30 min, GIP significantly (p < 0.0001) increased P1NP to 115.1 ± 2.2% of baseline compared with 103.1 ± 1.5% after placebo. Both GLP-2 and GIP(3-30)NH2 + GLP-2 significantly (p < 0.0001) decreased P1NP to 91.3 ± 1.1% and 88.1 ± 3.0% of baseline, respectively (at t = 45 min) compared with placebo.CONCLUSIONS: GIPR antagonism did not inhibit the GLP-2-induced reduction in bone resorption (CTX) in healthy young men. In contrast to GLP-2, GIP increased P1NP despite decreasing CTX indicating an uncoupling of bone resorption from formation. Thus, GLP-2 and GIP seem to exert separate effects on bone turnover in humans.CLINICAL TRIALS INFORMATION: ClinicalTrials.gov (NCT03159741).

KW - Bone formation

KW - Bone resorption

KW - CTX

KW - P1NP

KW - PTH

UR - http://www.scopus.com/inward/record.url?scp=85066141547&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2019.05.014

DO - 10.1016/j.bone.2019.05.014

M3 - Journal article

VL - 125

SP - 178

EP - 185

JO - Bone

JF - Bone

SN - 8756-3282

ER -

ID: 57192398