Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans

Louise L Lehrskov; Sasha Kjeldsen; Mark P Lyngbæk; Regitse Højgaard Chirstensen; Anne-Sophie Wedell-Neergaard; Line Søderlund; Niklas Rye Jørgensen; Rikke Krogh-Madsen; Nicolai J Wewer Albrechtsen; Helga Ellingsgaard

doi:10.1210/jendso/bvaa093

Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans

Louise L Lehrskov, Sasha Kjeldsen, Mark P Lyngbæk, Regitse Højgaard Chirstensen, Anne-Sophie Wedell-Neergaard, Line Søderlund, Niklas Rye Jørgensen, Rikke Krogh-Madsen, Nicolai J Wewer Albrechtsen, Helga Ellingsgaard

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Abstract

Context: Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited.

Objective: To investigate if IL-6 regulates bone remodeling in humans.

Design: Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies.

Participants: Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3.

Interventions: Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6.

Main outcomes measures: Effect of IL-6 on CTX levels.

Results: CTX was significantly (P < 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3).

Conclusions: IL-6 may not regulate bone remodeling in humans.

Original language	English
Article number	bvaa093
Journal	Endocrine Research
Volume	4
Issue number	9
Number of pages	12
ISSN	0743-5800
DOIs	https://doi.org/10.1210/jendso/bvaa093
Publication status	Published - 2020

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Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in HumansFinal published version, 605 KBLicence: CC BY-NC-ND

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Lehrskov, L. L., Kjeldsen, S., Lyngbæk, M. P., Chirstensen, R. H., Wedell-Neergaard, A.-S., Søderlund, L., Jørgensen, N. R., Krogh-Madsen, R., Wewer Albrechtsen, N. J., & Ellingsgaard, H. (2020). Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans. Endocrine Research, 4(9), Article bvaa093. https://doi.org/10.1210/jendso/bvaa093

@article{b29cf5e631f64bd9a70aa3e933f7d0a0,

title = "Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans",

abstract = "Context: Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited.Objective: To investigate if IL-6 regulates bone remodeling in humans.Design: Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies.Participants: Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3.Interventions: Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6.Main outcomes measures: Effect of IL-6 on CTX levels.Results: CTX was significantly (P < 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3).Conclusions: IL-6 may not regulate bone remodeling in humans.",

author = "Lehrskov, {Louise L} and Sasha Kjeldsen and Lyngb{\ae}k, {Mark P} and Chirstensen, {Regitse H{\o}jgaard} and Anne-Sophie Wedell-Neergaard and Line S{\o}derlund and J{\o}rgensen, {Niklas Rye} and Rikke Krogh-Madsen and {Wewer Albrechtsen}, {Nicolai J} and Helga Ellingsgaard",

note = "{\textcopyright} Endocrine Society 2020.",

year = "2020",

doi = "10.1210/jendso/bvaa093",

language = "English",

volume = "4",

journal = "Endocrine Research",

issn = "0743-5800",

publisher = "Taylor & Francis",

number = "9",

}

TY - JOUR

T1 - Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans

AU - Lehrskov, Louise L

AU - Kjeldsen, Sasha

AU - Lyngbæk, Mark P

AU - Chirstensen, Regitse Højgaard

AU - Wedell-Neergaard, Anne-Sophie

AU - Søderlund, Line

AU - Jørgensen, Niklas Rye

AU - Krogh-Madsen, Rikke

AU - Wewer Albrechtsen, Nicolai J

AU - Ellingsgaard, Helga

PY - 2020

Y1 - 2020

N2 - Context: Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited.Objective: To investigate if IL-6 regulates bone remodeling in humans.Design: Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies.Participants: Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3.Interventions: Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6.Main outcomes measures: Effect of IL-6 on CTX levels.Results: CTX was significantly (P < 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3).Conclusions: IL-6 may not regulate bone remodeling in humans.

AB - Context: Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited.Objective: To investigate if IL-6 regulates bone remodeling in humans.Design: Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies.Participants: Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3.Interventions: Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6.Main outcomes measures: Effect of IL-6 on CTX levels.Results: CTX was significantly (P < 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3).Conclusions: IL-6 may not regulate bone remodeling in humans.

U2 - 10.1210/jendso/bvaa093

DO - 10.1210/jendso/bvaa093

M3 - Journal article

C2 - 32793846

SN - 0743-5800

VL - 4

JO - Endocrine Research

JF - Endocrine Research

IS - 9

M1 - bvaa093

ER -