Advanced glycation end products and esRAGE are associated with bone turnover and incidence of hip fracture in older men

Lydia S Lamb, Helman Alfonso, Paul E Norman, Timothy M E Davis, Josephine Forbes, Gerald Müench, Felix Irrgang, Osvaldo P Almeida, Jonathan Golledge, Graeme J Hankey, Leon Flicker, Bu B Yeap

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover.

Aims: We tested the hypothesis that circulating advanced glycation end products (AGEs) and endogenous secretory receptor for AGEs (esRAGE) differentially modulate bone turnover and predict fracture risk in older men.

Participants: 3,384 community-dwelling men aged 70-89 years.

Methods: Collagen type I C-terminal cross-linked telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), and total osteocalcin (TOC) were assayed using immunoassay, and undercarboxylated osteocalcin (ucOC) following hydroxyapatite binding. Plasma N-carboxymethyllisine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained.

Results: Median age 76.3 years (interquartile range, 74.2-79.1). Plasma CML was measured in 3,011 men, methygloxal and glyoxal in 766 men and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal and esRAGE were similar in men without and with diabetes (all p>0.05). CML was positively associated with fasting glucose (r=0.06, p<0.001) and esRAGE was inversely associated (r=-0.08, p=0.045). EsRAGE was positively associated with bone formation (P1NP r=0.17, p<0.001; ucOC r=0.11, p=0.008; total OC 0.16, p<0.001). Incident hip fractures occurred in 106 men during follow-up. Men with CML in the third quartile of values had reduced incidence of hip fracture compared to men in the lowest quartile (HR 0.49, 95% CI 0.24-0.99, P=0.045).

Conclusions: Glycaemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men while CML predicts incidence of hip fracture.

Original languageEnglish
Pages (from-to)4224-4231
JournalThe Journal of clinical endocrinology and metabolism
Volume103
Issue number11
Early online date20 Aug 2018
DOIs
Publication statusPublished - Nov 2018

Fingerprint

Advanced Glycosylation End Products
Bone Remodeling
Hip Fractures
Bone
Glyoxal
Incidence
Osteocalcin
Pyruvaldehyde
Medical problems
Collagen Type I
Plasmas
Immunoassay
Durapatite
Advanced Glycosylation End Product-Specific Receptor
Mass spectrometry
Independent Living
Glucose
Osteogenesis
Bone Density
Fasting

Cite this

@article{801e59efbdbd4cc7b562136fdbcb4c47,
title = "Advanced glycation end products and esRAGE are associated with bone turnover and incidence of hip fracture in older men",
abstract = "Background: Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover.Aims: We tested the hypothesis that circulating advanced glycation end products (AGEs) and endogenous secretory receptor for AGEs (esRAGE) differentially modulate bone turnover and predict fracture risk in older men.Participants: 3,384 community-dwelling men aged 70-89 years.Methods: Collagen type I C-terminal cross-linked telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), and total osteocalcin (TOC) were assayed using immunoassay, and undercarboxylated osteocalcin (ucOC) following hydroxyapatite binding. Plasma N-carboxymethyllisine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained.Results: Median age 76.3 years (interquartile range, 74.2-79.1). Plasma CML was measured in 3,011 men, methygloxal and glyoxal in 766 men and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal and esRAGE were similar in men without and with diabetes (all p>0.05). CML was positively associated with fasting glucose (r=0.06, p<0.001) and esRAGE was inversely associated (r=-0.08, p=0.045). EsRAGE was positively associated with bone formation (P1NP r=0.17, p<0.001; ucOC r=0.11, p=0.008; total OC 0.16, p<0.001). Incident hip fractures occurred in 106 men during follow-up. Men with CML in the third quartile of values had reduced incidence of hip fracture compared to men in the lowest quartile (HR 0.49, 95{\%} CI 0.24-0.99, P=0.045).Conclusions: Glycaemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men while CML predicts incidence of hip fracture.",
author = "Lamb, {Lydia S} and Helman Alfonso and Norman, {Paul E} and Davis, {Timothy M E} and Josephine Forbes and Gerald M{\"u}ench and Felix Irrgang and Almeida, {Osvaldo P} and Jonathan Golledge and Hankey, {Graeme J} and Leon Flicker and Yeap, {Bu B}",
year = "2018",
month = "11",
doi = "10.1210/jc.2018-00674",
language = "English",
volume = "103",
pages = "4224--4231",
journal = "Journal of Endocrinology & Metabolism",
issn = "0021-972X",
publisher = "ENDOCRINE SOC",
number = "11",

}

Advanced glycation end products and esRAGE are associated with bone turnover and incidence of hip fracture in older men. / Lamb, Lydia S; Alfonso, Helman; Norman, Paul E; Davis, Timothy M E; Forbes, Josephine; Müench, Gerald; Irrgang, Felix; Almeida, Osvaldo P; Golledge, Jonathan; Hankey, Graeme J; Flicker, Leon; Yeap, Bu B.

In: The Journal of clinical endocrinology and metabolism, Vol. 103, No. 11, 11.2018, p. 4224-4231.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Advanced glycation end products and esRAGE are associated with bone turnover and incidence of hip fracture in older men

AU - Lamb, Lydia S

AU - Alfonso, Helman

AU - Norman, Paul E

AU - Davis, Timothy M E

AU - Forbes, Josephine

AU - Müench, Gerald

AU - Irrgang, Felix

AU - Almeida, Osvaldo P

AU - Golledge, Jonathan

AU - Hankey, Graeme J

AU - Flicker, Leon

AU - Yeap, Bu B

PY - 2018/11

Y1 - 2018/11

N2 - Background: Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover.Aims: We tested the hypothesis that circulating advanced glycation end products (AGEs) and endogenous secretory receptor for AGEs (esRAGE) differentially modulate bone turnover and predict fracture risk in older men.Participants: 3,384 community-dwelling men aged 70-89 years.Methods: Collagen type I C-terminal cross-linked telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), and total osteocalcin (TOC) were assayed using immunoassay, and undercarboxylated osteocalcin (ucOC) following hydroxyapatite binding. Plasma N-carboxymethyllisine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained.Results: Median age 76.3 years (interquartile range, 74.2-79.1). Plasma CML was measured in 3,011 men, methygloxal and glyoxal in 766 men and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal and esRAGE were similar in men without and with diabetes (all p>0.05). CML was positively associated with fasting glucose (r=0.06, p<0.001) and esRAGE was inversely associated (r=-0.08, p=0.045). EsRAGE was positively associated with bone formation (P1NP r=0.17, p<0.001; ucOC r=0.11, p=0.008; total OC 0.16, p<0.001). Incident hip fractures occurred in 106 men during follow-up. Men with CML in the third quartile of values had reduced incidence of hip fracture compared to men in the lowest quartile (HR 0.49, 95% CI 0.24-0.99, P=0.045).Conclusions: Glycaemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men while CML predicts incidence of hip fracture.

AB - Background: Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover.Aims: We tested the hypothesis that circulating advanced glycation end products (AGEs) and endogenous secretory receptor for AGEs (esRAGE) differentially modulate bone turnover and predict fracture risk in older men.Participants: 3,384 community-dwelling men aged 70-89 years.Methods: Collagen type I C-terminal cross-linked telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), and total osteocalcin (TOC) were assayed using immunoassay, and undercarboxylated osteocalcin (ucOC) following hydroxyapatite binding. Plasma N-carboxymethyllisine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained.Results: Median age 76.3 years (interquartile range, 74.2-79.1). Plasma CML was measured in 3,011 men, methygloxal and glyoxal in 766 men and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal and esRAGE were similar in men without and with diabetes (all p>0.05). CML was positively associated with fasting glucose (r=0.06, p<0.001) and esRAGE was inversely associated (r=-0.08, p=0.045). EsRAGE was positively associated with bone formation (P1NP r=0.17, p<0.001; ucOC r=0.11, p=0.008; total OC 0.16, p<0.001). Incident hip fractures occurred in 106 men during follow-up. Men with CML in the third quartile of values had reduced incidence of hip fracture compared to men in the lowest quartile (HR 0.49, 95% CI 0.24-0.99, P=0.045).Conclusions: Glycaemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men while CML predicts incidence of hip fracture.

U2 - 10.1210/jc.2018-00674

DO - 10.1210/jc.2018-00674

M3 - Article

VL - 103

SP - 4224

EP - 4231

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 11

ER -