Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men
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 b...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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Endocrine Society
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/73370 |
| _version_ | 1848762996684226560 |
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| author | Lamb, L. Alfonso, Helman Norman, P. Davis, T. Forbes, J. Müench, G. Irrgang, F. Almeida, O. Golledge, J. Hankey, G. Flicker, L. Yeap, B. |
| author_facet | Lamb, L. Alfonso, Helman Norman, P. Davis, T. Forbes, J. Müench, G. Irrgang, F. Almeida, O. Golledge, J. Hankey, G. Flicker, L. Yeap, B. |
| author_sort | Lamb, L. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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 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; 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. |
| first_indexed | 2025-11-14T10:56:27Z |
| format | Journal Article |
| id | curtin-20.500.11937-73370 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:56:27Z |
| publishDate | 2018 |
| publisher | Endocrine Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-733702018-12-13T09:35:22Z Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men Lamb, L. Alfonso, Helman Norman, P. Davis, T. Forbes, J. Müench, G. Irrgang, F. Almeida, O. Golledge, J. Hankey, G. Flicker, L. Yeap, B. 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 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; 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/73370 10.1210/jc.2018-00674 Endocrine Society restricted |
| spellingShingle | Lamb, L. Alfonso, Helman Norman, P. Davis, T. Forbes, J. Müench, G. Irrgang, F. Almeida, O. Golledge, J. Hankey, G. Flicker, L. Yeap, B. Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men |
| title | Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men |
| title_full | Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men |
| title_fullStr | Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men |
| title_full_unstemmed | Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men |
| title_short | Advanced Glycation End Products and esRAGE Are Associated With Bone Turnover and Incidence of Hip Fracture in Older Men |
| title_sort | advanced glycation end products and esrage are associated with bone turnover and incidence of hip fracture in older men |
| url | http://hdl.handle.net/20.500.11937/73370 |