Subcutaneous GIP and GLP-2 inhibit nightly bone resorption in postmenopausal women: A preliminary study

Kirsa Skov-Jeppesen; Simon Veedfald; Sten Madsbad; Jens Juul Holst; Mette Marie Rosenkilde; Bolette Hartmann

doi:10.1016/j.bone.2021.116065

Subcutaneous GIP and GLP-2 inhibit nightly bone resorption in postmenopausal women: A preliminary study

Kirsa Skov-Jeppesen, Simon Veedfald, Sten Madsbad, Jens Juul Holst, Mette Marie Rosenkilde, Bolette Hartmann

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Abstract

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX).

OBJECTIVE: The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption.

METHODS: Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP + GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP).

RESULTS: Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 min after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 min after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 min after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP).

CONCLUSION: Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.

Original language	English
Article number	116065
Journal	Bone
Volume	152
Number of pages	7
ISSN	8756-3282
DOIs	https://doi.org/10.1016/j.bone.2021.116065
Publication status	Published - 2021

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Subcutaneous GIP and GLP-2 inhibit nightly bone resorption in postmenopausal women: A preliminary studyFinal published version, 3.58 MBLicence: CC BY

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@article{fc7ad12ffee945bf8dee2bc1958eac09,

title = "Subcutaneous GIP and GLP-2 inhibit nightly bone resorption in postmenopausal women: A preliminary study",

abstract = "BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX).OBJECTIVE: The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption.METHODS: Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP + GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP).RESULTS: Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 min after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 min after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 min after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP).CONCLUSION: Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.",

author = "Kirsa Skov-Jeppesen and Simon Veedfald and Sten Madsbad and Holst, {Jens Juul} and Rosenkilde, {Mette Marie} and Bolette Hartmann",

year = "2021",

doi = "10.1016/j.bone.2021.116065",

language = "English",

volume = "152",

journal = "Bone",

issn = "8756-3282",

publisher = "Elsevier",

}

TY - JOUR

T1 - Subcutaneous GIP and GLP-2 inhibit nightly bone resorption in postmenopausal women

T2 - A preliminary study

AU - Skov-Jeppesen, Kirsa

AU - Veedfald, Simon

AU - Madsbad, Sten

AU - Holst, Jens Juul

AU - Rosenkilde, Mette Marie

AU - Hartmann, Bolette

PY - 2021

Y1 - 2021

N2 - BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX).OBJECTIVE: The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption.METHODS: Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP + GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP).RESULTS: Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 min after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 min after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 min after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP).CONCLUSION: Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.

AB - BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX).OBJECTIVE: The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption.METHODS: Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP + GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP).RESULTS: Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 min after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 min after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 min after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP).CONCLUSION: Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.

U2 - 10.1016/j.bone.2021.116065

DO - 10.1016/j.bone.2021.116065

M3 - Journal article

C2 - 34153529

VL - 152

JO - Bone

JF - Bone

SN - 8756-3282

M1 - 116065

ER -