Hyperhomocysteinemia decreases bone blood flow

Tyagi, Neetu; Vacek, Thomas P.; Fleming, John T.; Vacek, Jonathan; Tyagi, Suresh C.

doi:10.2147/vhrm.s15844

Cited by 18 publications

(6 citation statements)

References 25 publications

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“…Interestingly, higher Hcy levels and decreased vitamin B12 were observed in Hcy-treated rats than in control rats. In Hcy-treated rats, the elevated Hcy level also reduced the bone's blood flow, which contributed to compromised bone biomechanical properties [201].…”

Section: Hhcy As a Risk Factor Of Impaired Healingmentioning

confidence: 99%

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

et al. 2021

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Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

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Section: Hhcy As a Risk Factor Of Impaired Healingmentioning

confidence: 99%

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

et al. 2021

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“…Consequentially, increased severity of celiac lesions is associated with higher homocysteine levels [62]. Aberrant homocysteine levels are related to an increased risk for venous thromboembolism, vascular disease, osteoporosis and adverse pregnancy outcomes [72][73][74].…”

Section: Comorbidities Potentially Related To Nutrient Deficiencies Imentioning

confidence: 99%

Narrative Review: Nutrient Deficiencies in Adults and Children with Treated and Untreated Celiac Disease

et al. 2020

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Nutrient deficiencies are well recognized as secondary consequences of celiac disease (CD) and closely related to the clinical presentation of affected patients. Despite their clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD, the usefulness of their assessment at the time of diagnosis and during follow-up. This review aims to provide an overview of nutrient deficiencies among pediatric and adult CD patients at diagnosis and on a gluten-free diet (GFD), and their potential causes in CD. Secondly, we review their impact on CD management strategies including the potential of nutrient supplementation. A search of Medline, Pubmed and Embase until January 2019 was performed. Despite a high variability between the reported deficiencies, we noted that nutrient deficiencies occur frequently in children and adults with CD at diagnosis and during treatment with a GFD. Both inadequate dietary intake and/or diminished uptake due to intestinal dysfunction contribute to nutrient deficiencies. Most deficiencies can be restored with (long-term) treatment with a GFD and/or supplementation. However, some of them persist while others may become even more prominent during GFD. Our results indicate a lack of comprehensive evidence on the clinical efficacy of nutrient supplementation in CD management highlighting the need for further studies.

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“…The tibia blood flow index of the control group was significantly higher compared with the Hcy-treated group. Moreover, tibia bone density was unchanged in Hcy-treated groups [72]. Hence, we propose a mechanism by which superoxide anion created by HHcy may react with NO and reduce NO bioavailability [73].…”

Section: Hcy and Vasculaturementioning

confidence: 99%

The role of homocysteine in bone remodeling

Vacek

Kalani

Voor

et al. 2013

Clinical Chemistry and Laboratory Medicine

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Bone remodeling is a very complex process. Homocysteine (Hcy) is known to modulate this process via several known mechanisms such as increase in osteoclast activity, decrease in osteoblast activity and direct action of Hcy on bone matrix. Evidence from previous studies further support a detrimental effect on bone via decrease in bone blood flow and an increase in matrix metalloproteinases (MMPs) that degrade extracellular bone matrix. Hcy binds directly to extracellular matrix and reduces bone strength. There are several bone markers that can be used as parameters to determine how high levels of plasma Hcy (hyperhomocysteinemia, HHcy) affect bone such as: hydroxyproline, N-terminal collagen 1 telopeptides. Mitochondrion serves an important role in generating reactive oxygen species (ROS). Mitochondrial abnormalities have been identified during HHcy. The mechanism of Hcy-induced bone remodeling via the mitochondrial pathway is largely unknown. Therefore, we propose a mitochondrial mechanism by which Hcy can contribute to alter bone properties. This may occur both through generations of ROS that activate MMPs and could be extruded into matrix to degrade bone matrix. However, there are contrasting reports on whether Hcy affects bone density, with some reports in favour and others not. Earlier studies also found an alteration in bone biomechanical properties with deficiencies of vitamin B12, folate and HHcy conditions. Moreover, existing data opens speculation that folate and vitamin therapy act not only via Hcy-dependent pathways but also via Hcy-independent pathways. However, more studies are needed to clarify he mechanistic role of Hcy during bone diseases.

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Hyperhomocysteinemia decreases bone blood flow

Cited by 18 publications

References 25 publications

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

Narrative Review: Nutrient Deficiencies in Adults and Children with Treated and Untreated Celiac Disease

The role of homocysteine in bone remodeling

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