vitamin-b-12 and Fractures--Bone

Although there are several factors related to bone diseases such as physical activity, gender (oestrogen), race/ethnicity, smoking and alcohol habits, nutrition is a modifiable risk factor that could be employed to prevent or manage the onset of bone health diseases such as osteoporosis in humans. Aside from calcium and vitamin D, B vitamins are a group of water-soluble vitamins that play a vital role in cell metabolism. In this review, current evidence on B vitamins and bone health is assessed. Clinical trials (interventions) indicate that treatment with B vitamins impact the concentrations of total plasma/serum homocysteine concentrations (tHcy); however, most studies have reported the lack of an effect of low homocysteine concentrations on bone turnover markers, bone mineral density or fracture risks. Current studies have been inconsistent in their reports on the role of B vitamins and homocysteine in bone health. More data are therefore required to show the mechanism and effect of tHcy and B vitamins on bone mineral density, bone metabolism and fracture risk.

Topics: Bone and Bones; Bone Density; Folic Acid; Fractures, Bone; Homocysteine; Humans; Osteoporosis; Vitamin B 12; Vitamin B Complex

In vitro and animal model studies have shown that vitamin B (VB) deficiency has negative consequences on bone as a result of direct or mediated activity of hyperhomocysteinemia. However, there are still no precise indications regarding a possible VB role in order to maintain bone health. So, the aim of this narrative review was to consider state of the art correlation between VB dietary intake, blood levels and supplementation and bone health (bone mineral density (BMD), bone turnover markers and fractures risk) in humans. This review includes 29 eligible studies. Considering VB blood levels, the 14 studies considered have shown that low serum folate can be a risk factor for reduced BMD and fractures in the elderly, particularly women; no independent association was found for other VB. Studies that evaluate the relationship between VB dietary intake and BMD are only 2; one, conducted on 1869 women, demonstrated a positive effect of folate intake on BMD. Another demonstrated a dose-dependent inverse relationship between vitamin B6 dietary intake and risk of hip fracture, but only for 35298 female participants. Regarding the relationship between BV supplementation and bone health (9 studies with only VB and 4 with other nutrients), all studies that considered patients with hyperhomocysteinemia or with low folate blood levels, are in agreement in demonstrating that folate supplementation (500mcg- 5mg) is useful in improving BMD. In conclusion, a request for folate and homocysteine blood levels in elderly patients with osteopenia/osteoporosis is mandatory. For patients with hyperhomocysteinemia or with low folate blood levels, folate supplementation (500mcg-5mg) is crucial.

Topics: Aged; Bone Density; Dietary Supplements; Eating; Female; Folic Acid; Fractures, Bone; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B Complex

To consolidate information available on the effect of vitamin B12 on bone mineral density and fracture risk, with emphasis on clinical trials, observational and longitudinal data conducted in humans.. A systematic review of the literature of the past decade on the role of vitamin B12 in bone mineral density and fracture risk in subjects of all ages and both sexes was performed by means of a PubMed, Science Direct, Medline and SciELO database search. Articles included in this review were identified using the search terms: B12 Vitamin and Bone Mineral Density and Vitamin B12 and Risk of Fractures. Evidence quality of the included articles was evaluated by GRADE system.. A total of 25 original studies were identified. After reviewing the titles and abstracts of articles, only 17 articles met the inclusion criteria. The present review provides evidence that the role of vitamin B12 on bone mineral density or fracture risk should be further elucidated. Controversies are explained by heterogeneity of methodologies used for the diagnosis of vitamin B12 and also by differences among populations investigated on the studies.. A real effect of vitamin B12 deficiency in bone health and the mechanisms associated with bone metabolism is not well established yet. It is extremely important to carry out more clarifying studies about this theme, especially with vulnerable groups such as postmenopausal and elderly women, as is well-known that they are greatly affected by deficiency of this vitamin.

Topics: Adult; Bone Density; Clinical Trials as Topic; Dietary Supplements; Female; Fractures, Bone; Humans; Male; Risk Factors; Vitamin B 12; Vitamin D Deficiency

B vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies.. Relevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation.. Based on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover.. B vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future.

Topics: Biomarkers; Bone Remodeling; Dietary Supplements; Folic Acid; Fractures, Bone; Humans; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 6

Proton pump inhibitors are widely used in the treatment of acid-related diseases because they are considered to be effective and safe. In the past 10 years the use of proton pump inhibitors increased by over three folds, which is not associated with the increased prevalence of acid-related diseases obviously. However, like any other drugs, they have potential side effects. In recent years many studies have been published about the correlation between long-term proton pump inhibitor therapy and the increase of bone fractures. Most studies showed that long-term proton pump inhibitor therapy moderately increased fracture risk. The underlying mechanisms of increased number of bone fractures are not clarified yet. However, chronic acid suppression caused by long-term proton pump inhibitor therapy may play a crucial role in decreased absorption of calcium and vitamin B12 and, therefore, indirectly affecting the bones resulting in a decrease of bone mineral density. The available data suggest that proton pump inhibitors should be used with caution in patients with increased risk of osteoporosis.. A protonpumpagátlók alkalmazása elterjedt a gyomorsav okozta megbetegedések kezelésében, mivel ezek a szerek meglehetősen hatékonyak és biztonságosan alkalmazhatóak. Alkalmazásuk viszont az elmúlt 10 évben több mint háromszorosára nőtt, ami egyértelműen nincs arányban a savval összefüggő kórképek növekedésével. Ez különösképpen azért is aggályos, mert a legtöbb gyógyszernek – csakúgy, mint ezeknek a szereknek is – vannak mellékhatásaik. Az utóbbi években több tanulmány is megjelent, melyekben a hosszú távú protonpumpagátló kezelés és a csonttörések gyakoriságának növekedése közötti összefüggést vizsgálták. A tanulmányok többségében kimutatták, hogy a hosszú távú protonpumpagátló kezelés kismértékben növeli a csonttörések kockázatát. A gyakoribb törések hátterében álló mechanizmusok nem tisztázottak kellőképpen, azonban valószínűleg a terápia hatására kialakuló krónikus hypoaciditas játszik benne szerepet, mely befolyásolja a kalcium és a B12-vitamin felszívódását, illetve közvetetten befolyásolja a csontrendszert is, csökkentve a csontsűrűséget. A rendelkezésre álló adatok alapján mindenképpen ajánlott az óvatosság protonpumpagátló kezelés indítása esetén olyan betegek körében, akiknél fokozott az osteoporosis kialakulásának kockázata. Orv. Hetil., 2013, 154, 1005–1009.

Topics: Bone Density; Calcium, Dietary; Drug Administration Schedule; Fractures, Bone; Gastric Acid; Humans; Intestinal Absorption; Osteoporosis; Proton Pump Inhibitors; Vitamin B 12

Vitamin B12 and folic acid deficiency are associated with a higher serum concentration of homocysteine. A high serum homocysteine is a risk factor for fractures. Both vitamins play a role in the remethylation of homocysteine to methionine. The pathophysiology from a high serum homocysteine to fractures is not completely clear, but might involve bone mineral density, bone turnover, bone blood flow, DNA methylation, and/or physical function and fall risk. Genetic variation, especially polymorphisms of the gene encoding for methylenetetrahydrofolate reductase may play a role in homocysteine metabolism and fracture risk. It is uncertain whether supplementation with vitamin B12 and folate can decrease fracture incidence. One double blind clinical trial in post-stroke patients showed that these B vitamins could decrease hip fracture incidence, but the results of further clinical trials should be awaited before a definite conclusion can be drawn.

Topics: Bone and Bones; Bone Density; Dietary Supplements; Folic Acid; Fractures, Bone; Homocysteine; Humans; Prevalence; Vitamin B 12

To investigate current concerns regarding the use of proton-pump inhibitors (PPIs) in older adults.. A literature search was conducted in MEDLINE (1948 to April week 3 2011) to identify relevant publications. Key words searched included proton-pump inhibitor, safety, adverse events, elderly, and older adults. Additional data sources were obtained through a bibliographic review of selected articles.. Relevant studies conducted in older adults published in English that examined risks associated with the use of PPIs were included in this review.. The older adult population in the United States is growing at an astounding rate. With the increase in age, there are many factors that make the elderly susceptible to acid-related gastrointestinal disorders that require treatment with PPIs. However, PPI use in the elderly has been shown to lead to a number of health concerns. Recent data have shown that PPI use is associated with an increased risk of fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin and mineral deficiencies, and drug interactions. These concerns will be further investigated and weighed against the benefits of PPI use in this population.. Patient-specific characteristics must be taken into consideration when recommending and/or prescribing PPIs to older adults.

Topics: Aged; Clostridioides difficile; Community-Acquired Infections; Drug Interactions; Fractures, Bone; Humans; Proton Pump Inhibitors; Risk; Vitamin B 12

Proton pump inhibitors (PPI) are one of the most widely used classes of drugs. PPIs have a very favorable safety profile, and it is unusual for a patient to stop them because of side effects. However, with increasing numbers of patients chronically taking PPIs for gastroesophageal reflux disease and other common, persistent conditions, the long-term potential adverse effects are receiving increasing attention. An insufficiently studied area receiving much attention is the long-term effect of chronic acid suppression on the absorption of vitamins and nutrients. This increased attention results from the reported potential adverse effect of chronic PPI treatment leading to an increased occurrence of bone fractures. Interest in this area has led to examination of the effects of PPIs on calcium absorption/metabolism and numerous cohort, case-control, and prospective studies of their ability to affect bone density and cause bone fractures. In this article, these studies are systematically examined, as are studies of the effects of chronic PPI use on absorption of VB(12), iron, and magnesium. Studies in each area have led to differing conclusions, but when examined systematically, consistent results of several studies support the conclusion that long-term adverse effects on these processes can have important clinical implications.

Topics: Animals; Calcium; Fractures, Bone; Gastric Acid; Humans; Intestinal Absorption; Iron; Magnesium; Proton Pump Inhibitors; Vitamin B 12; Zollinger-Ellison Syndrome

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence ofa common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Dementia; Diet; Female; Folic Acid; Fractures, Bone; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Neural Tube Defects; Pregnancy; Public Health; Risk Factors; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia (HHCY) has been suggested as a new risk factor for osteoporosis. Recent epidemiological, clinical and experimental studies provide a growing body of data, which is reviewed in this article. Epidemiological and (randomized) clinical trials suggest that HHCY increases fracture risk, but has minor effects on bone mineral density. Measurement of biochemical bone turnover markers indicates a shift of bone metabolism towards bone resorption. Animal studies confirm these observations showing a reduced bone quality and stimulation of bone resorption in hyperhomocysteinemic animals. Homocysteine (HCY) has been found to accumulate in bone by collagen binding. Cell culture studies demonstrate that high HCY levels stimulate osteoclasts but not osteoblasts, indicating again a shift of bone metabolism towards bone resorption. Regarding B-vitamins, only a few in vivo studies with equivocal results have been published. However, two large cell culture studies confirm the results obtained with exogenous HCY administration. In addition, HHCY seems to have adverse affects on extracellular bone matrix by disturbing collagen crosslinking. In conclusion, existing data suggest that HHCY (and possibly B-vitamin deficiencies) adversely affects bone quality by a stimulation of bone resorption and disturbance of collagen crosslinking.

Topics: Animals; Bone Density; Folic Acid Deficiency; Fractures, Bone; Humans; Hyperhomocysteinemia; Osteoporosis; Vitamin B 12; Vitamin B 6; Vitamin B Deficiency

As for any chronic disease, adherence to osteoporosis treatment is low. Folates and vitamin B12 decrease hip fracture risk in elderly Japanese with stroke. Raloxifene (Evista) decreases the incidence of positive estrogen receptor breast cancer and could prevent cardiovascular events in patients at high risk. Strontium ranelate (Protélos) prevents hip fracture in elderly women. The action of alendronate (Fosamax) on bone mineral density and markers of bone remodelling is of higher amplitude than that of risedronate (Actonel). Once monthly ibandronate (Bonviva) increases bone mineral density in post menopausal women with osteoporosis. Excessive suppression of bone remodelling and osteonecrosis of the yaws could be related to bisphosphonate intake.

Topics: Bone Density; Bone Density Conservation Agents; Bone Resorption; Chronic Disease; Folic Acid; Fractures, Bone; Humans; Osteonecrosis; Osteoporosis; Vitamin B 12

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of 2 pathways: remethylation, which requires folic acid and B-12 coenzymes, and transsulfuration, which requires pyridoxal-5'-phosphate, the B-6 coenzyme. Data from several studies suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies we have shown that plasma total homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B-6 as well as vitamin B-12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid artery stenosis of at least 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and CVD mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. This multitude of relationships between elevated plasma total homocysteine and diseases that afflict the elderly point to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is homocysteine itself or whether homocysteine is merely a marker remains to be determined.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cardiovascular Diseases; Carotid Stenosis; Cohort Studies; Dementia; Diet; Female; Folic Acid; Fractures, Bone; Heart Failure; Homocysteine; Humans; Hyperhomocysteinemia; Male; Massachusetts; Middle Aged; Risk Factors; Stroke; Vascular Diseases; Vitamin B 12; Vitamin B 6

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk.. Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease.. A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present.. This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.

Topics: Aged; Cardiovascular Diseases; Cerebrovascular Disorders; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Fractures, Bone; Homocysteine; Humans; Male; Odds Ratio; Osteoporotic Fractures; Placebos; Risk Factors; Vitamin B 12

Young Indian women may be at risk of poor bone health due to malnutrition. The aim of this study was to examine the effects on bone metabolism of a nutritional supplement in women aged 25 to 44. The nutritional supplement was a protein-rich beverage powder fortified with multi-micronutrients including calcium (600 mg), vitamin D (400 IU), and vitamin K (55 mcg) per daily serving, while a placebo supplement was low-protein non-fortified isocaloric beverage powder. This 6-month randomised, controlled trial showed favorable changes in bone turnover markers (decreased) and calcium homeostasis; such changes in older adults have been associated with slowing of bone loss and reduced fracture risk. For example, serum CTX decreased by about 30% and PINP by about 20% as a result of the increase in calcium intake. There were also changes in the ratio of carboxylated to undercarboxylated osteocalcin and such changes have been linked to a slowing of bone loss in older subjects. For example, the ratio increased by about 60% after 3 months as a result in the improvement in vitamin K status. Finally, there were improvements in the status of B vitamins, and such changes have been associated with reductions in homocysteine, but it is uncertain whether this would affect fracture risk. The product was generally well tolerated. This study shows the nutritional supplement holds promise for improved bone health among young Indian women.

Topics: Adult; Bone Diseases, Metabolic; Bone Remodeling; Calcium; Calcium, Dietary; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Fractures, Bone; Homeostasis; Humans; India; Osteocalcin; Osteoporosis; Premenopause; Vitamin B 12; Vitamin D; Vitamin K

Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk. As vitamin B12 and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration.. The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration (≥ 12 μmol/L). One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet. In both tablets 15 μg (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers, physical performance and physical activity including falls, nutritional intake and status, cognitive function, depression, genetics and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam, the Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University, (Wageningen, the Netherlands), the latter acting as coordinator.. To our best knowledge, the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population. We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013. The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures.. The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514).

Topics: Aged; Aged, 80 and over; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Fractures, Bone; Humans; Incidence; Male; Osteoporosis; Treatment Outcome; Vitamin B 12

Topics: Aged; Cardiovascular Diseases; Drug Therapy, Combination; Female; Folic Acid; Fractures, Bone; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Male; Middle Aged; Proportional Hazards Models; Pyridoxine; Risk Factors; Treatment Outcome; Vitamin B 12

In the progress of bone metabolism, homocysteine (Hcy) and B vitamins play substantial roles. However, the causal associations of homocysteine, B-vitamin concentrations with bone mineral density (BMD), and fractures remain unclear. Therefore, we employed a two-sample Mendelian randomization (MR) design to infer the causal effects of Hcy and B vitamins on BMD and fractures.. We selected instrumental variables from large genome-wide association studies (GWASs). Specifically, the exposures mainly included Hcy (sample size: 44,147), vitamin B12 (sample size: 45,576), folate (sample size: 37,465), and vitamin B6 (sample size: 1,864). The outcome variables included total body BMD (sample size: 66,628), heel BMD (sample size: 142,487), femoral neck BMD (sample size: 32,735), lumbar spine BMD (sample size: 28,498), and forearm BMD (sample size: 8143). Additionally, the total body BMD in several age strata was also included. Furthermore, the fractures of the forearm, femoral neck, lumbar spine, heel corresponding with the BMD regions, and femoral neck and lumbar spine BMD in men and women, separately, were added as additional outcomes. Two-sample MR approaches were utilized in this study. Inverse variance weighting (IVW) was adopted as the main analysis. MR-PRESSO, MR-Egger, the weighted median estimate, and multivariable MR were performed as sensitivity methods.. In the main analysis, Hcy concentrations have an inverse association with heel BMD (Beta = 0.046, 95% confidence interval (CI) -0.073 to -0.019,. Our findings indicated that there exist the inversely causal effects of Hcy and vitamin B12 on BMD in certain body sites and age strata. These give novel clues for intervening bone-related diseases in public health and nutrition.

Topics: Bone Density; Female; Fractures, Bone; Genome-Wide Association Study; Homocysteine; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Vitamin B 12; Vitamin B Complex

Several studies consistently showed vegans having a higher risk of bone fractures compared to individuals from other diet groups. While researchers have focused on several factors as possible explanation of these findings, both dietary (e.g. calcium) and non-dietary (e.g. weight/BMI status), the widespread inadequate vitamin B12 (B12) status among vegans as a risk factor for bone fractures has not received adequate scrutiny. The detrimental impact of inadequate B12 status on bone tissue is both direct, via the impairment of the insulin-like growth hormone 1 and taurine synthesis, and indirect, induced through its hyperhomocysteinemic effect, via at least the following mechanisms: 1) reducing bone mineral content and density by accumulating in the extracellular matrix, 2) reducing osteoblasts and increasing osteoclasts function, 3) reducing blood flow to bone tissue, 4) inducing apoptosis via the reactive oxygen-species-mediated mitochondrial pathway, and 5) obstructing the formation of collagen cross-links, impeding lyslyl oxidase, and hampering insolubility of fibrils. Considering the widespread B12 deficiency prevalence among vegans, its role in bone fracture risk should not be overlooked.

Topics: Bone and Bones; Diet, Vegetarian; Fractures, Bone; Humans; Risk Factors; Vegans; Vitamin B 12; Vitamin B 12 Deficiency

Falls and fractures constitute a major cause of morbidity and mortality among older adults. Although falls and fractures share similar risk factors, there is no integrated approach to identifying secondary causes of both entities. We report a cost-effective approach to identify metabolic causes of falls and fractures in the clinical setting.. Falls and fractures are a major cause of morbidity and mortality among older adults. Metabolic disorders contributing to the combined risk of falls and fractures are frequent but often go undetected. The most efficient and cost-effective laboratory screening strategy to unmask these disorders remains unknown. The purpose of this study was to identify the most cost-effective laboratory tests to detect undiagnosed metabolic contributors and to decide treatment of these disorders in older persons.. This is a cross-sectional study design, which included all participants attending the Falls & Fractures Clinic, Nepean Hospital (Penrith, Australia) between 2008 and 2013. Chemistry profile included 25(OH) vitamin D, parathyroid hormone (PTH), albumin, creatinine, calcium, phosphate, vitamin B-12, folate, and thyroid-stimulating hormone (TSH) for all patients, and serum testosterone in men. The number of new diagnoses identified and their cost-effectiveness (cost in US$ per patient screened and cost per new diagnosis) were calculated.. A total of 739 participants (mean age 79, 71 % female) were assessed. Among 233 participants with complete laboratory tests, previously undiagnosed disorders were identified in 148 (63.5 %). Vitamin D deficiency (27 %) and hyperparathyroidism (21.5 %) were the most frequent diagnoses. A testing strategy including serum vitamin D, calcium, PTH, creatinine/estimated glomerular filtration rate (eGFR), and TSH for all patients and serum testosterone in men would have been sufficient to identify secondary causes of falls and fractures in 94 % of patients at an estimated cost of $190.19 per patient screened and $257.64 per diagnosis.. The minimum cost-effective battery for occult metabolic disorders in older adults at risk of falls and fractures should include serum vitamin D, PTH, TSH, creatinine/eGFR, testosterone (in men), and calcium.

Topics: Accidental Falls; Aged; Aged, 80 and over; Australia; Blood Chemical Analysis; Calcium; Cost-Benefit Analysis; Creatinine; Cross-Sectional Studies; Female; Folic Acid; Fractures, Bone; Humans; Hyperparathyroidism; Male; Metabolic Diseases; Middle Aged; Parathyroid Hormone; Phosphates; Risk Factors; Serum Albumin; Testosterone; Thyrotropin; Vitamin B 12; Vitamin D; Vitamin D Deficiency

Topics: Fractures, Bone; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Vitamin B 12; Vitamin B 12 Deficiency

This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment.. We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C) and methionine synthase reductase (MTRR 66A > G) single nucleotide polymorphisms (SNPs) on total body BMD (BMD(TB)) and lumbar spine BMD (BMD(LS)) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥ 4 years (n = 68).. Carriers of the MTHFR 677 T-allele showed a lower baseline BMD(TB) than non-carriers (-0.38 SDS vs. +0.55 SDS, p = 0.01) and BMD(TB) remained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMD(TB) (p = 0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMD(TB) compared with non-carriers. Combining these two SNPs, patients carrying ≥ 2 risk alleles had a significantly lower BMD(TB) (-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A > C had higher homocysteine levels, this SNP was not related to BMD(TB). BMD(LS) of carriers was similar to non-carriers of the investigated SNPs.. The MTHFR 677C>T SNP and the MTRR 66A >G SNP were identified as determinants of impaired BMD(TB) in childhood ALL patients.

Topics: Absorptiometry, Photon; Adolescent; Biomarkers, Tumor; Bone Density; Case-Control Studies; Child; Child, Preschool; Ferredoxin-NADP Reductase; Folic Acid; Fractures, Bone; Genotype; Germ Cells; Homocysteine; Humans; Infant; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Vitamin B 12

Folate, vitamin B2 (riboflavin), and vitamin B12 may affect bone directly or through an effect on plasma homocysteine levels. Previously, a positive association has been found between plasma levels and bone mineral density (BMD) as well as risk of fracture. However, there are limited data on whether dietary intakes affect bone. Our aim was to investigate whether intake of folate, vitamin B2) and vitamin B12, as assessed by food records affects BMD and fracture risk. In a population-based cohort including 1,869 perimenopausal women from the Danish Osteoporosis Prevention Study, associations between intakes and BMD were assessed at baseline and after 5 years of follow-up. Moreover, associations between intakes and 5- and 10-year changes in BMD as well as risk of fracture were studied. Intakes of folate, vitamin B2, and vitamin B12 were 417 (range 290-494) microg/day, 2.70 (range 1.70-3.16) mg/day, and 4.98 (range 3.83-6.62) microg/day, respectively, i.e., slightly above the intakes recommended by the United Nations Food and Agriculture Organization. At year 5, but not at baseline, cross-sectional analyses showed positive correlations between daily intake from diet and from diet plus supplements of folate and BMD at the femoral neck (P < 0.01). However, no associations were found between intakes and changes in BMD. During 10 years of follow-up, 360 subjects sustained a fracture. Compared with 1,440 controls, logistic regression analyses revealed no difference in intakes between cases and controls. A high dietary intake of folate, but not vitamin B2 or B12, exerts positive effects on BMD; but further studies are needed to confirm this association.

Topics: Adult; Bone and Bones; Bone Density; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Denmark; Dietary Supplements; Female; Femur Neck; Folic Acid; Follow-Up Studies; Food, Formulated; Fractures, Bone; Humans; Lumbar Vertebrae; Middle Aged; Nutritional Requirements; Osteoporosis, Postmenopausal; Prospective Studies; Radiography; Riboflavin; Time; Time Factors; Vitamin B 12

Water-soluble vitamins influence the development of an adequate structure of bone tissue, but there is scant information relating them with osteoporotic fractures. We analyze whether serum vitamin C, vitamin B12, and erythrocyte folate, or dietary intake of vitamin C and folate, are related with osteoporotic fractures in the elderly. A hospital-based case-control study was carried out at the Hospital of Jaén (167 cases, 167 controls), Spain. Cases were defined as patients aged 65 or more years with a low-energy fracture. Controls were people without fracture, matched for age and sex with cases. Diet was assessed by a semi-quantitative food frequency questionnaire. Serum vitamin C was measured using high-performance liquid chromatography (HPLC). Folic acid and vitamin B12 were measured using procedures of competitive or immunometric immunoassay. Multivariable analyses were also fitted to adjust for confounding using analysis of covariance (for the comparison of adjusted means) and conditional logistic regression (for estimating adjusted odds ratios). A statistically significant difference between cases and controls for vitamin C blood levels was found, being higher for controls (p = 0.01). Analysis of the association between serum vitamin C and fracture risk showed a linear trend (p = 0.03) with a significantly reduced risk for the upper quartile (OR = 0.31; 95% CI 0.11-0.87). The intake of vitamin C, folic acid, and B12 was not related to fracture risk, nor was there any association with erythrocyte folate or serum vitamin B12. In conclusion, serum vitamin C levels were lower in cases with osteoporotic fractures than in controls.

Topics: Aged; Aging; Ascorbic Acid; Case-Control Studies; Causality; Chromatography, High Pressure Liquid; Diet; Diet Records; Female; Folic Acid; Fractures, Bone; Geriatric Assessment; Humans; Immunoassay; Male; Multivariate Analysis; Odds Ratio; Osteoporosis; Risk Factors; Spain; Surveys and Questionnaires; Vitamin B 12

Topics: Cardiovascular Diseases; Female; Folic Acid; Fractures, Bone; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia may contribute to the development of osteoporosis. The relationship of Hcy and vitamin B12 with bone turnover markers, BUA, and fracture incidence was studied in 1267 subjects of the Longitudinal Aging Study Amsterdam. High Hcy and low vitamin B12 concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk.. Hyperhomocysteinemia may contribute to the development of osteoporosis. Vitamin B12 is closely correlated to homocysteine (Hcy). The main objective of our study was to examine the association of Hcy and vitamin B12 status and the combined effect of these two with broadband ultrasound attenuation (BUA), bone turnover markers, and fracture.. Subjects were 615 men and 652 women with a mean age of 76 +/- 6.6 (SD) years of the Longitudinal Aging Study Amsterdam (LASA). At baseline (1995/1996), blood samples were taken after an overnight fast for dairy products. Plasma Hcy was measured with IMx, serum vitamin B12 with competitive immunoassay (IA) luminescence, serum osteocalcin (OC) with immunoradiometric assay (IRMA), and urinary excretion of deoxypyridinoline (DPD) with competitive IA and corrected for creatinine (Cr) concentration. CVs were 4%, 5%, 8%, and 5%, respectively. BUA was assessed in the heel bone twice in both the right and left calcaneus. Mean BUA value was calculated from these four measurements. CV was 3.4%. After baseline measurements in 1995, a 3-year prospective follow-up of fractures was carried out until 1998/1999. Subjects were grouped by using two different approaches on the basis of their vitamin B12 concentration, normal versus low (<200 pM) or lowest quartile (Q1) versus normal quartiles (Q2-Q4), and Hcy concentration, normal versus high (>15 microM) or highest quartile (Q4) versus normal quartiles (Q1-Q3). Analysis of covariance was performed to calculate mean values of BUA, OC, and DPD/Cr(urine) based on the specified categories of Hcy and vitamin B12 and adjusted for several confounders (potential confounders were age, sex, body weight, body height, current smoking [yes/no], mobility, cognition). The relative risk (RR) of any fracture was assessed with Cox regression analysis. Quartiles were used when Hcy and vitamin B12 were separately studied in their relationship with fracture incidence.. Fourteen percent of the men and 9% of the women had high Hcy (>15 microM) and low vitamin B12 (<200 pM) concentrations. Women with vitamin B12 levels <200 pM and Hcy concentrations >15 microM had lower BUA, higher DPD/Cr, and higher OC concentrations than their counterparts. In men, no differences were found between the different Hcy and vitamin B12 categories in adjusted means of BUA, OC, or DPD/Cr(urine). Twenty-eight men and 43 women sustained a fracture during the 3-year follow-up period. The adjusted RR for fractures (95% CI) for men with high Hcy and/or low vitamin B12 concentrations was 3.8 (1.2-11.6) compared with men with normal Hcy and vitamin B12 concentrations. Women with high Hcy and/or low vitamin B12 concentrations had an adjusted RR for fractures of 2.8 (1.3-5.7).. High Hcy and low vitamin B12 concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk.

Topics: Aged; Aged, 80 and over; Body Weight; Bone and Bones; Cohort Studies; Creatine; Female; Fractures, Bone; Homocysteine; Humans; Immunoassay; Immunoradiometric Assay; Male; Middle Aged; Osteocalcin; Osteoporosis; Proportional Hazards Models; Regression Analysis; Risk; Risk Factors; Time Factors; Ultrasonography; Vitamin B 12

A nutritional survey performed in 46 elderly long-term surgical patients in an orthopedic ward showed that, although a sufficient hospital diet was served, the intakes of vitamin B12 were borderline, while the intakes of folate were inadequate inmost patients. Low energy intake combined with a high consumption of titbits in bedridden patients was assumed to be responsible for this malnourishment.

Topics: Aged; Female; Folic Acid; Food; Fractures, Bone; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Nutritional Requirements; Surgical Procedures, Operative; Time Factors; Vitamin B 12

Severe osteomalacia with secondary hyperparathyroidism was observed in a 19-year-old mentally retarded girl, who had been treated for several years with antiepileptic drugs. Vitamin D3 orally administered in low doses led to complete reversal of all symptoms and normalization of blood chemistry, X-ray pictures demonstrated healing of all lesions. It is suggested that the alterations of vitamin-D metabolism occuring during the administration of phenobarbital and hydantion are of importance only in patients with an already lowered intake of vitamin D3 or reduced exposure to ultraviolet rays.

Topics: Adult; Anticonvulsants; Bicarbonates; Blood Proteins; Calcium; Cholecalciferol; Cholesterol; Creatinine; Female; Fractures, Bone; Hematocrit; Hemoglobins; Humans; Hyperparathyroidism; Osteomalacia; Vitamin B 12

Topics: Adult; Arthritis; Contusions; Drug Combinations; Female; Flufenamic Acid; Fractures, Bone; Humans; Joint Diseases; Male; Middle Aged; Osteoporosis; Pyridoxine; Sciatica; Spinal Injuries; Sprains and Strains; Thiamine; Vitamin B 12; Vitamins

Topics: Fractures, Bone; Humans; Methionine; Pyrogens; Vitamin B 12; Wound Healing

Topics: Adult; Aged; Analgesics; Bone Diseases; Coenzymes; Fractures, Bone; Humans; Injections, Intramuscular; Joint Dislocations; Middle Aged; Pain; Vitamin B 12

Topics: Aged; Anemia, Pernicious; Female; Femoral Fractures; Fibula; Fractures, Bone; Humans; Male; Middle Aged; Tibial Fractures; Vitamin B 12; Wound Healing

Topics: Adult; Aged; Aminopyrine; Analgesics; Fractures, Bone; Herpes Zoster; Humans; Joint Diseases; Middle Aged; Neuralgia; Pain; Pyridoxine; Quinolines; Rheumatic Diseases; Spinal Diseases; Vitamin B 12

Topics: Bone Diseases; Fractures, Bone; Humans; Intervertebral Disc Displacement; Joint Diseases; Neuralgia; Peripheral Nerve Injuries; Phospholipids; Sciatica; Vitamin B 12

Topics: Back Pain; Brachial Plexus Neuritis; Corrinoids; Fractures, Bone; Hepatitis; Humans; Intervertebral Disc Displacement; Orthopedics; Pyridoxine; Sciatica; Syphilis; Thiamine; Traumatology; Vitamin B 12; Vitamin B Complex; Vitamins