The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review

Herrmann, Markus; Schmidt, Johannes Peter; Umanskaya, Natalia; Wagner, Alexandra; Taban-Shomal, Omid; Widmann, Thomas; Colaianni, Graziana; Wildemann, Britt; Herrmann, Wolfgang

doi:10.1515/cclm.2007.362

Cited by 105 publications

(98 citation statements)

References 78 publications

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“…Animal studies in mice and rats have already revealed that modulating Hcy levels by means of methionine-enriched diets caused an increase in bone resorption [34,35], indicating that nutrient intervention can modulate bone resorption via alteration of Hcy levels. In the elderly, Hcy levels can effectively be reduced by means of B 12 and folate supplementation [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B 12 deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B 12 , Hcy, and MMA on differentiation and activity of bone cells. B 12 deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B 12 deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B 12 , Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B 12 did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B 12 deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels.Osteoporosis is a complex multifactorial disease with a strong genetic component, but lifestyle factors are also important for maintenance of bone mass. Nutrition is one of the factors that contributes to bone health. During the first decades of life, adequate intake of calcium and vitamin D is essential to establish peak bone mass (see [1,2] and references therein). It has also been observed that nutritional deficiencies can cause impaired growth and skeletal abnormalities during childhood [3], while in adults inadequate intake of nutrients such as proteins, vitamins, and minerals has been associated with loss of bone quality [2,4]. Nutritional deficiency is very common in the elderly, emphasizing that adequate nutrient intake may slow down the age-related loss of bone mass.A challenge in nutrition research is to identify food components that contribute to the maintenance of bone health. During the last years, vitamin B 12 has gained particular attention since a number of epidemiological studies have reported a correlation between B 12 status and bone quality and fracture risk [5][6][7][8][9]. The micronutrient B 12 is involved as a cofactor in two enzymatic reactions [10]. The enzyme methionine synthase requires B 12 for the remethylation of homocysteine (Hcy) into methionine. The other enzyme dependent on B 12 is methylmalonyl-CoA mutase, which catalyzes the conversion of methylmalonyl-CoA into succinyl-CoA. As a consequence of B 12 deficiency, these

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Section: Discussionmentioning

confidence: 99%

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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“…As reviewed recently, results from existing epidemiological and intervention studies are equivocal. (38) Previous animal studies analyzing the effect of HHCY on bone used exclusively methionine or homocystine supplementation to induce HHCY (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Experimental Folate and Vitamin B12 Deficiency Does Not Alter Bone Quality in Rats

Herrmann

Wildemann

Wagner

et al. 2009

Journal of Bone and Mineral Research

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Hyperhomocysteinemia (HHCY) has been linked to fragility fractures and osteoporosis. Folate and vitamin B 12 deficiencies are among the main causes of HHCY. However, the impact of these vitamins on bone health has been poorly studied. This study analyzed the effect of folate and vitamin B 12 deficiency on bone in rats. We used two groups of rats: a control group (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10). VitDef animals were fed for 12 wk with a folate-and vitamin B 12 -free diet. Co animals received an equicaloric control diet. Tissue and plasma concentrations of homocysteine (HCY), S-adenosyl-homocysteine (SAH), and S-adenosyl-methionine (SAM) were measured. Bone quality was assessed by biomechanical testing (maximum force of an axial compression test; F max ), histomorphometry (bone area/total area; B.Ar./ T.Ar.], and the measurement of biochemical bone turnover markers (osteocalcin, collagen I C-terminal crosslaps [CTX]). VitDef animals developed significant HHCY (Co versus VitDef: 6.8 ± 2.7 versus 61.1 ± 12.8 mM, p < 0.001) that was accompanied by a high plasma concentration of SAH (Co versus VitDef: 24.1 ± 5.9 versus 86.4 ± 44.3 nM, p < 0.001). However, bone tissue concentrations of HCY, SAH, and SAM were similar in the two groups. Fmax, B.Ar./T.Ar., OC, and CTX did not differ between VitDef and Co animals, indicating that bone quality was not affected. Folate and vitamin B 12 deficiency induces distinct HHCY but has no effect on bone health in otherwise healthy adult rats. The unchanged HCY metabolism in bone is the most probable explanation for the missing effect of the vitamin-free diet on bone.

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“…The T-allele variant (valine type) has a lower MTHFR activity than the wild type (C-allele or alanine type) and is also associated with moderately elevated homocysteine levels [57]. An elevated homocysteine level has been recognized as a significant risk factor for fractures [60][61][62], independent of age and BMD, because it is caused by abnormal collagen cross-links during bone calcification [63][64][65]. Clinical evidence regarding the role of the MTHFR C677T polymorphism in BMD remains controversial [66].…”

Section: Gwas Related To Osteoporosis and Osteoporotic Fracturesmentioning

confidence: 99%

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

Urano

Inoue

2015

Endocr J

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Abstract. Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD) and an increased susceptibility to fractures. Evidence from genetic studies indicates that BMD, a complex quantitative trait with a normal distribution, is genetically controlled. Genome-wide association studies (GWAS) as well as studies using candidate gene approaches have identified single-nucleotide polymorphisms (SNPs) that are associated with BMD, osteoporosis and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding WNT/β-catenin signaling proteins. Understanding the genetics of osteoporosis will help to identify novel candidates for diagnostic and therapeutic targets. Genetic factors are also important for the development of sarcopenia, which is characterized by a loss of lean body mass, and obesity, which is characterized by high fat mass. Hence, in this review, we discuss the genetic factors, identified by genetic studies, which regulate the body components related to osteoporosis, sarcopenia, and obesity.

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The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review

Cited by 105 publications

References 78 publications

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

Experimental Folate and Vitamin B12 Deficiency Does Not Alter Bone Quality in Rats

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

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