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

Journal Publication ResearchOnline@JCU
Lamb, Lydia S.;Alfonso, Helman;Norman, Paul E.;Davis, Timothy M.E.;Forbes, Josephine;Muench, Gerald;Irrgang, Felix;Almeida, Osvaldo P.;Golledge, Jonathan;Hankey, Graeme J.;Flicker, Leon;Yeap, Bu B.
Jonathan Golledge
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: A total of 3384 community-dwelling men aged 70 to 89 years. Methods: Collagen type I C-terminal cross-linked telopeptide, 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-carboxymethyllysine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained. Results: Median age was 76.3 years (interquartile range, 74.2 to 79.1 years). Plasma CML was measured in 3011 men, methylglyoxal and glyoxal in 766 men, and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal, and esRAGEwere similar inmenwithout andwith diabetes (all P>0.05). CML was positively associated with fasting glucose (r = 0.06, P < 0.001), and esRAGE was inversely associated (r = 20.08, P = 0.045). esRAGE was positively associated with bone formation (P1NP, r = 0.17, P, 0.001; ucOC, r = 0.11, P = 0.008; TOC, r = 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 with men in the lowest quartile (hazard ratio, 0.49; 95% CI, 0.24 to 0.99; P = 0.045). Conclusions: Glycemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men, whereas CML predicts incidence of hip fracture.

Journal

Journal of Clinical Endocrinology and Metabolism

Publication Name

N/A

Volume

103

ISBN/ISSN

1945-7197

Edition

N/A

Issue

11

Pages Count

8

Location

N/A

Publisher

Endocrine Society

Publisher Url

N/A

Publisher Location

N/A

Publish Date

N/A

Url

N/A

Date

N/A

EISSN

N/A

DOI

10.1210/jc.2018-00674