Homocysteine Levels and the Risk of Osteoporotic Fracture

Meurs, Joyce B. J. van; Dhonukshe-Rutten, R.A.M.; Pluijm, Saskia M F; Klift, Marjolein van der; Jonge, Robert de; Lindemans, Jan; Groot, Lisette C. P. G. M. de; Hofman, Albert; Witteman, Jacqueline C. M.; Leeuwen, Johannes P.T.M. van; Breteler, Monique M.B.; Lips, P.; Pols, Huibert A. P.; Uitterlinden, André G.

doi:10.1056/nejmoa032546

Cited by 661 publications

(440 citation statements)

References 30 publications

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“…In 2004, two landmark studies performed in the Netherlands and the USA produced consistent findings in terms of the magnitude of increased risk of fracture associated with mild elevations in homocysteine (36,37) . In subsequent years, further studies from the USA, the Netherlands and Norway similarly demonstrated increases in fracture risk associated with elevated homocysteine concentrations (31)(32)(33)35) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 91%

“…Indeed, Van Meurs et al (36) found a significant increase in fracture risk associated with the highest (compared with the lowest) quartile of homocysteine concentrations, but no significant differences in BMD values across homocysteine quartiles. Conversely, some studies have found an association of B-vitamin biomarkers with BMD but not with fracture risk.…”

Section: Evidence From Observational Studiesmentioning

confidence: 98%

“…In the past decade, numerous large observational studies have provided evidence to support a role for homocysteine and/or low B-vitamin status in fracture risk (Table 1) (12,(29)(30)(31)(32)(33)(34)(35)(36)(37) . In 2004, two landmark studies performed in the Netherlands and the USA produced consistent findings in terms of the magnitude of increased risk of fracture associated with mild elevations in homocysteine (36,37) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 99%

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B-vitamins and bone in health and disease: the current evidence

et al. 2014

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Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677C→T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

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Section: Evidence From Observational Studiesmentioning

confidence: 91%

Section: Evidence From Observational Studiesmentioning

confidence: 98%

Section: Evidence From Observational Studiesmentioning

confidence: 99%

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B-vitamins and bone in health and disease: the current evidence

et al. 2014

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“…1 Hyperhomocysteinemia has also been linked to increased risk of Alzheimer's disease, 2 neural tube defects, 3 complications during pregnancy, 4 inflammatory bowel disease, 5 and osteoporosis. 6 The role of Hcy in disease is unclear. After many years of study and impressive progress, it is still not yet known if Hcy causes disease, is a consequence of it, or is simply a biomarker.…”

Section: Homocysteine and Cysteine In Human Healthmentioning

confidence: 99%

Detection of Homocysteine and Cysteine

et al. 2005

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At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular diseases, Alzheimer's disease, neural tube defects, and osteoporosis. Both 1 and cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by which 1 and 3 are involved in disease states are relatively unclear. Herein, we describe simple methods for detecting either Hcy or Cys in the visible spectral region with the highest selectivity reported to date without using biochemical techniques or preparative separations. Simple methods and readily available reagents allow for the detection of Cys and Hcy in the range of their physiologically relevant levels. New HPLC postcolumn detection methods for biological thiols are reported. The potential biomedical relevance of the chemical mechanisms involved in the detection of 1 is described.

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“…Several studies have reported that low plasma B 12 levels are associated with reduced bone quality [5,8,9,13,14], but this relation has not been observed by others [15][16][17]. More consistently, however, are the observations that increased Hcy may be a predictive factor for fracture risk [13][14][15][18][19][20][21]. Also, elevated MMA levels have been associated with osteoporosis in the elderly [14] and low bone mineral density (BMD) in adolescents [6].…”

mentioning

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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Homocysteine Levels and the Risk of Osteoporotic Fracture

Abstract: An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.

Cited by 661 publications

References 30 publications

B-vitamins and bone in health and disease: the current evidence

B-vitamins and bone in health and disease: the current evidence

Detection of Homocysteine and Cysteine

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

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