Serum homocysteine, folate and vitamin B12 in patients with Paget’s disease of bone: the effect of zoledronic acid

Polyzos, Stergios A.; Anastasilakis, Athanasios D.; Efstathiadou, Zoe; Litsas, I.; Kita, Marina; Panagiotou, Athanasios; Παπαθεοδώρου, Αθανάσιος; Arsos, Georgios; Moralidis, Efstratios; Barmpalios, Georgios; Zafeiriadou, Efthimia; Triantafillidou, Efthimia; Makrigiannaki, Eleni; Terpos, Evangelos

doi:10.1007/s00774-009-0131-1

Cited by 9 publications

(9 citation statements)

References 24 publications

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“…To our knowledge, there are only two studies correlating serum Hcy levels with NAFLD severity, but the results are controversial. Higher Hcy levels in NASH and NAFLD patients have been reported in one study [9], whereas other authors have described lower Hcy levels in NASH patients as compared to steatosis subjects [48]. Both studies agree that the serum Hcy might be a noninvasive biomarker for the assessment of NAFLD [9,48].…”

Section: Discussionsupporting

confidence: 57%

“…Higher Hcy levels in NASH and NAFLD patients have been reported in one study [9], whereas other authors have described lower Hcy levels in NASH patients as compared to steatosis subjects [48]. Both studies agree that the serum Hcy might be a noninvasive biomarker for the assessment of NAFLD [9,48]. Population and methodological differences may account for the contradictory findings in the literature.…”

Section: Discussionmentioning

confidence: 41%

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Methylenetetrahydrofolate Reductase Gene Polymorphism and Serum Homocysteine Levels in Nonalcoholic Fatty Liver Disease

Brochado

Domenici²,

Martinelli³

et al. 2013

Ann Nutr Metab

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Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by hepatic fat accumulation in the absence of alcohol consumption. Hyperhomocysteinemia is considered an independent risk factor for liver diseases, and the genetic polymorphisms C677T and A1298C in the MTHFR gene have been linked to hyperhomocysteinemia. The purpose of this study was to investigate serum homocysteine (Hcy) concentrations and the MTHFR C677T and A1298C polymorphisms as risk factors for the development of NAFLD. Methods: One hundred and thirty-four Brazilian patients with biopsy-proven NAFLD and 134 healthy controls were recruited. The MTHFR C677T and A1298C polymorphisms were detected through polymerase chain reaction restriction fragment length polymorphism. Serum Hcy levels were determined by chemiluminescence. Results: Serum Hcy levels were higher in NAFLD patients as compared to control subjects, but there were no differences between patients with steatosis and nonalcoholic steatohepatitis. The NAFLD and control groups did not differ in genotypic and allelic frequencies of the MTHFR C677T and A1298C polymorphisms, either. Elevated plasma Hcy levels were positively correlated with age in the NAFLD subjects. Conclusion: The MTHFR C677T and A1298C polymorphisms are not genetic risk factors for the development of NAFLD. Higher Hcy levels exist in NAFLD subjects, but they are not associated with liver disease severity.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 41%

Methylenetetrahydrofolate Reductase Gene Polymorphism and Serum Homocysteine Levels in Nonalcoholic Fatty Liver Disease

Brochado

Domenici²,

Martinelli³

et al. 2013

Ann Nutr Metab

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“…Other researchers and we have shown that Hcy increases collagen turnover in various pathological conditions (Miller et al, 2002; Polyzos et al, 2010). Here we report that FA mitigates Hcy induced collagen turn over by decreasing the expression of Col4a and Col1a in the cochlear tissue of CBS+/− mice.…”

Section: Discussionmentioning

confidence: 47%

Folic acid improves inner ear vascularization in hyperhomocysteinemic mice

Kundu¹,

Munjal²,

Tyagi³

et al. 2012

Hearing Research

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More than 29 million adults in the United States have been diagnosed with hearing loss. Interestingly, elevated homocysteine (Hcy) levels, known as hyperhomocysteinemia (HHcy) is also associated with impaired hearing. However, the associated mechanism remains obscure. The collagen receptor such as discoidin domain receptor 1 and matrix metalloproteinase (MMP) play a significant role in inner ear structure and function. We hypothesize that HHcy increases hearing thresholds by compromise in inner ear vasculature resulted from impaired Hcy metabolism, increased oxidative stress, collagen IVa and collagen la turnover. The treatment with folic acid (FA) protects elevated hearing thresholds and prevents reduction in vessel density by lowering abundant collagen deposition and oxidative stress in inner ear. To test this hypothesis we employed 8 weeks old male wild type (WT), cystathionine-beta-synthase heterozygote knockout (CBS+/−) mice, WT+FA (0.0057 μg/g/day, equivalent to a 400 μg/70 kg/day human dose in drinking water); and CBS(+/−)+FA. The mice were treated for four weeks. The hearing thresholds were determined by recording the auditory brainstem responses. Integrity of vessels was analyzed by perfusion of horseradish peroxidase (HRP) tracer. Endothelial permeability was assessed, which indicated restoration of HRP leakage by FA treatment. A total Hcy level was increased in stria vascularis (SV) and spiral ligament (SL) of CBS+/− mice which was lowered by FA. Interestingly, FA treatment lowered Col IVa Immunostaining by affecting its turnover. The levels of MMP-2, -9, methylenetetrahydrofolate reductase (MTHFR) and cystathione gamma lyase (CSE) were measured by Western blot analysis. The oxidative stress was high in SV and SL of CBS+/− compared to WT however the treatment with FA lowered oxidative stress in CBS+/− mice. These data suggested that hearing loss in CBS+/− mice was primarily due to leakage in inner ear circulation, also partly by induced collagen imbalance, increase in Hey and oxidative stress in inner ear.

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“…Polyzos et al reported baseline increase in hcy levels in patients with Paget's disease along with a decrease in bone forming markers like bone-specific alkaline phosphatase and serum folate levels. [12] In the present study, in osteosarcoma patients a significant positive correlation was observed between serum folate and hcy levels [r = 0.473, P < 0.01, Figure 1]. Also, a significant negative correlation was observed between Vitamin B 12 and hcy levels in osteosarcoma patients [r = −0.573, P < 0.001, Figure 2].…”

Section: Discussionsupporting

confidence: 49%