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, Muench, Gerald, Irrgang, Felix, Almeida, Osvaldo P., Golledge, Jonathan, Hankey, Graeme J., Flicker, Leon, and Yeap, Bu B. (2018) Advanced glycation end products and esRAGE are associated with bone turnover and incidence of hip fracture in older men. Journal of Clinical Endocrinology and Metabolism, 103 (11). pp. 4224-4231.

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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.

Item ID: 57084
Item Type: Article (Research - C1)
ISSN: 1945-7197
Funders: Sylvia and Charles Viertel Charitable Foundation, National Heart Foundation of Australia (NHF), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHF G11P5662
Date Deposited: 13 Feb 2019 07:31
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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