Pentosidine and carboxymethyl-lysine associate differently with prevalent osteoporotic vertebral fracture and various bone markers

Nakano, Masaki; Nakamura, Yukio; Suzuki, Takehiko; Miyazaki, Akiko; Takahashi, J.; Saito, Mitsuru; Shiraki, Masataka

doi:10.1038/s41598-020-78993-w

Cited by 32 publications

(22 citation statements)

References 46 publications

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“…There was no significant relationship between hip BMD and serum CML concentrations observed in our study. This finding is consistent with reports by Barzilay and colleagues ( 40 ) and Nakano and colleagues ( 54 ) and indicates that this association between CML and fracture is likely through bone quality and not bone quantity. However, the study by Nakano and colleagues ( 54 ) also reported a significant negative correlation between lumbar spine BMD and serum CML levels, suggesting that the relationship of CML with BMD may be site‐specific.…”

Section: Discussionsupporting

confidence: 93%

“…This finding contrasts with reports of an increased risk of hip fracture with higher concentrations of serum CML in older adults with and without diabetes, ( 40,41 ) and an association between tissue level CML accumulation in femoral cortical bone and its fracture properties. ( 23 ) Similar to our study finding, Nakano and colleagues ( 54 ) also reported no independent association of CML with the presence of vertebral fracture in women without diabetes. These differences suggest that, under T2D, CML may accumulate early or in greater amount due to increased hyperglycemia and oxidative stress, ( 10,14‐17 ) as well as higher surface to volume ratio of cancellous bone tissue ( 55 ) that occupies large proportion of vertebrae and contributes to its load bearing and biomechanical properties.…”

Section: Discussionsupporting

confidence: 89%

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Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes

Dhaliwal

Ewing

Vashishth

et al. 2020

Journal of Bone and Mineral Research

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Accumulation of advanced glycation end‐products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non‐fluorescent AGEs. We examined associations of carboxy‐methyl‐lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non‐diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non‐diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24–1.79 per 1‐SD increase in log CML) but not in non‐diabetes (HR 1.03; 95% CI, 0.94–1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin‐C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. © 2021 American Society for Bone and Mineral Research (ASBMR).

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes

Dhaliwal

Ewing

Vashishth

et al. 2020

Journal of Bone and Mineral Research

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“…These dependencies are so strong that IHD and GFR can be considered as a predictor of uorescent AGE content, and IHD and hypertension as a predictor of high pentosidine levels. These correlations have been described earlier [50,52,53]. This is a logical consequence of the fact that glycation causes the formation of cross-links between collagen bers and other proteins responsible for biochemical properties in the arteries, making them more rigid, unable to dilate properly, and manifesting in hypertension [54].…”

Section: Discussionsupporting

confidence: 61%

Glycation Markers in the Geriatrics Patients

Kuzan

Królewicz

Kustrzeba−Wójcicka

et al. 2021

Preprint

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Background: Medical care for geriatric patients is a great challenge, mainly due to overlapping various deficits relevant to physiologic ageing with numerous coexisting diseases, of which the most common are diabetes mellitus and atherosclerosis. In case of diabetes, glycation process is intensified, which accelerates atherosclerosis development and diabetic complications. Our goal was to investigate the relationship between the classical biochemical parameters of diabetes and atherosclerosis (fasting glucose, glycated hemoglobin (HbA1c), low and high density lipoproteins (LDL, HDL), triglycerides, etc.), as well as parameters which may indicate a nephropathy (creatinine, glomerular filtration rate – GFR), and the parameters strictly related to glycation. Methods: We analyzed the patients' serum concentration of fluorescent glycation products, concentration of soluble receptor for advanced glycation products (sRAGE), lipoprotein receptor-1 (LOX-1), galectin 3 (GAL3), scavenger receptor class A (SR-A) and scavenger receptor class B (SR-BI), as well as the level of lipid peroxidation and free amine content. Results: Among the identified correlations, the most interesting are the following : sRAGE with triglycerides (r = 0.47); sRAGE with SR-BI (r=0.47); SR-BI with LOX-1 (r=0.31), and SR-BI with HDL (r=-0.30). It has been shown that pentosidine and fluorescent AGEs as well as reactive free amine contents are significantly higher in elderly patients with ischemic heart disease. Fluorescent AGEs and pentosidine are also significantly higher in patients with arterial hypertension. The influence of diabetes therapy on parameters related to peroxidation and glycation was also analyzed. Malondialdehyde turned to be higher in patients with diabetes mellitus type 2 not treated with insulin or metformin than in those treated with both medications (p=0.052). GAL3 was found to be lower both in persons without diabetes and in diabetics treated with metformin (p=0.005). LOX1 was higher in diabetic patients not treated with metformin or insulin, and lowest in diabetics treated with both insulin and metformin, with the effect of metformin reducing LOX1 levels (p=0.039). Conclusions: Our results were the basis for a discussion about the diagnostic value in clinial practice of LOX-1 and GAL3 in geriatric patients with diabetes and also provide grounds for inferring the therapeutic benefits of insulin and metformin treatment.

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“…Advanced glycation end products (AGEs), such as pentosidine, were associated with vertebral fracture, but not with lumbar BMD. [ 47 ]. Imbalance of serum homocysteine (Hcy) level has also been reported as a pathological biomarker of osteoporotic fractures [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Dietary Total Antioxidant Capacity with Bone Mass and Osteoporosis Risk in Korean Women: Analysis of the Korea National Health and Nutrition Examination Survey 2008–2011

2021

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Antioxidant intake has been suggested to be associated with a reduced osteoporosis risk, but the effect of dietary total antioxidant capacity (TAC) on bone health and the risk of osteoporosis remains unclear. We aimed to assess the hypothesis that dietary TAC is positively associated with bone mass and negatively related to the risk of osteoporosis in Korean women. This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. Dietary TAC was estimated using task automation and an algorithm with 24-h recall data. In total, 8230 pre- and postmenopausal women were divided into four groups according to quartiles of dietary TAC. Dietary TAC was negatively associated with the risk of osteoporosis (odds ratio, 0.73; 95% confidence interval, 0.54–0.99; p-value = 0.045) in postmenopausal women, but not in premenopausal women. Dietary TAC was positively associated with bone mineral content (BMC) and bone mineral density of the femoral neck and lumbar spine in postmenopausal women and BMC of the total femur and lumbar spine in premenopausal women. Our study suggests that dietary TAC is inversely associated with the risk of osteoporosis in postmenopausal women and positively associated with bone mass in both pre- and postmenopausal women.

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Pentosidine and carboxymethyl-lysine associate differently with prevalent osteoporotic vertebral fracture and various bone markers

Cited by 32 publications

References 46 publications

Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes

Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes

Glycation Markers in the Geriatrics Patients

Association of Dietary Total Antioxidant Capacity with Bone Mass and Osteoporosis Risk in Korean Women: Analysis of the Korea National Health and Nutrition Examination Survey 2008–2011

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