Medical School, University of Western Australia, Perth, Western Australia, Australia.
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia.
J Clin Endocrinol Metab. 2018 Nov 1;103(11):4224-4231. doi: 10.1210/jc.2018-00674.
Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover.
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.
A total of 3384 community-dwelling men aged 70 to 89 years.
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.
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).
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.
尽管骨密度保持不变且骨转换减少，糖尿病仍与骨折风险增加相关。
我们检验了这样一个假设，即循环晚期糖基化终产物（AGEs）和内源性 AGE 受体（esRAGE）是否会以不同的方式调节骨转换并预测老年男性的骨折风险。
3384 名年龄在 70 至 89 岁之间的社区居住男性。
使用免疫测定法测定Ⅰ型胶原 C 端交联端肽、Ⅰ型胶原 N 端前肽（P1NP）和总骨钙素（TOC），并使用羟磷灰石结合后测定非羧化骨钙素（ucOC）。使用免疫测定法测定血浆 N-羧甲基赖氨酸（CML）和 esRAGE。使用质谱法测定甲基乙二醛和乙二醛。确定新发髋部骨折。
中位年龄为 76.3 岁（四分位距，74.2 至 79.1 岁）。在 3011 名男性中测量了血浆 CML，在 766 名男性中测量了甲基乙二醛和乙二醛，在 748 名男性中测量了 esRAGE。无糖尿病和糖尿病男性的血浆 CML、甲基乙二醛、乙二醛和 esRAGE 相似（均 P>0.05）。CML 与空腹血糖呈正相关（r=0.06，P<0.001），而 esRAGE 则呈负相关（r=-0.08，P=0.045）。esRAGE 与骨形成呈正相关（P1NP，r=0.17，P<0.001；ucOC，r=0.11，P=0.008；TOC，r=0.16，P<0.001）。在随访期间，有 106 名男性发生髋部骨折。与最低四分位数的男性相比，第三四分位数的 CML 值的男性髋部骨折发生率降低（风险比，0.49；95%CI，0.24 至 0.99；P=0.045）。
在老年男性中，血糖与 CML 呈正相关，与 esRAGE 呈负相关。循环 esRAGE 调节老年男性的骨转换，而 CML 则预测髋部骨折的发生率。
