Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women

Salari, Pooneh; Abdollahi, Mohammad; Heshmat, Ramin; Meybodi, Hamidreza Aghaei; Razi, Farideh

doi:10.1186/s40199-014-0062-9

Cited by 19 publications

(17 citation statements)

References 40 publications

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“…However, the study, by Sato and colleagues, was recently retracted, invalidating those positive findings . Similarly, results of most previous trials testing the effects of B vitamins on markers of bone turnover have also failed to demonstrate significant effects. However, these studies have also suffered from small sample size and most were relatively short‐term trials of 3 to 6 months …”

Section: Introductionmentioning

confidence: 99%

Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial

Stone

Lui

Christen

et al. 2017

Journal of Bone and Mineral Research

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Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12, B6 and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or 3 or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces non-spine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 non-spine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on non-spine fracture risk (Relative Hazard = 1.08; 95% confidence interval 0.88 – 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6, or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle aged and older women at high risk of CV disease.

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Section: Introductionmentioning

confidence: 99%

Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial

Stone

Lui

Christen

et al. 2017

Journal of Bone and Mineral Research

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“…The key characteristics of the trials were summarized in Table 1 . Four RCTs assessed the effect of B vitamin supplementation on fracture risk [ 15 – 18 ] and 4 RCTs assessed the change of bone formation markers after B vitamin supplementation [ 13 , 14 , 19 , 20 ]. All of the studies reported significantly lowered plasma Hcy in the intervention group than in the control group.…”

Section: Resultsmentioning

confidence: 99%

“…Four RCTs with 329 participants assessed the change of bone formation markers after B vitamin supplementation [ 13 , 14 , 19 , 20 ]. One study [ 13 ] gave patients folate, B6, and B12 simultaneously, 1 study [ 19 ] used both folate and VB12, 1 study [ 14 ] provided VB6 and VB12, and 1 study [ 20 ] only provided folate. Although the combination of B vitamins varied in different studies, all of them reported that the intervention significantly reduced plasma Hcy.…”

Section: Resultsmentioning

confidence: 99%

“…Generally, compared with placebo, supplementation of B vitamins had no significant effect on ALP (WMD: −0.96, 95%CI: −4.10 to 2.18, p=0.55, I 2 =0%) ( Figure 4A ) and CTX (WMD: −0.01, 95%CI: −0.06 to 0.07, p=0.87, I 2 =0%) ( Figure 4B ). Salari et al [ 20 ] study measured urine CTX instead of serum CTX and their results also showed that folate supplementation could not change urine CTX (supplementation vs. placebo, p=0.285).…”

Section: Resultsmentioning

confidence: 99%

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Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

Ruan¹,

Gong²,

Jinsong³

et al. 2015

Med Sci Monit

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BackgroundB 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.Material/MethodsRelevant 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.ResultsBased 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.ConclusionsB 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.

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“…Folic acid supplementation reduces the homocysteine level, which is a risk factor for osteoporosis (33). Salari et al reported that 1 mg of folic acid supplementation for 6 months had an impact on the rate of bone metabolism (34). In another study, folic acid deficiency, but not vitamin B12 deficiency, was found to be an important factor in vertebral BMD decline (35).…”

Section: Discussionmentioning

confidence: 99%

Bone Metabolism Alterations in Patients with Common Variable Immune Deficiency: A Retrospective Cohort Study

Aytekin¹,

Çölkesen²,

Yıldız³

et al. 2020

Asthma Allergy Immunol

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Objective: Common variable immunodeficiency (CVID) is a relatively frequent primary immunodeficiency disorder characterized by impaired B cell differentiation with hypogammaglobulinemia in the European Society for Immunodeficiencies (ESID) registry system. Increased inflammatory cytokines, prolonged and/or recurrent infections, gastrointestinal complications, and anti-inflammatory medications are risk factors for diminished bone mineral density (BMD) in CVID patients. Materials and Methods: The study group included 32 patients with CVID (19 males and 13 females; mean age: 37.33 ± 13.70 years, 40.6% female), who had been followed up on a regular basis for a period of four years. The patients were categorized into two groups according to their BMD: low BMD and normal BMD. Results: Seventeen patients (8 females and 9 males) had normal BMD (mean age 34.94 ± 11.41 years, 47.1% female) and fifteen patients (5 females and 10 males) had low BMD (mean age 40.03 ± 15.87 years, 33.3% female). In the low BMD group, three patients had osteoporosis and 12 patients had osteopenia. Univariate regression analysis revealed that lymphopenia (odds ratio, OR:6.562, 95% confidence interval, CI: 1.095-39.324, p=0.039) was significantly associated with low BMD. Multivariate regression analysis showed that higher alkaline phosphatase (ALP) levels (OR:1.017, 95% CI 1.001-1.033, p=0.041), lymphopenia (OR:11.028, 95% CI 1.326-91.709, p=0.026), and lower folic acid levels (OR:1.284, 95% CI 1.007-1.637, p=0.043) were also independent predictors for low BMD. Conclusion: Even with some limitations such as the small number for the study population, a single center experience, and a crosssectional design, we recommend that clinical immunologists should be alert for diminished BMD in CVID patients, especially those with low folic acid and high ALP levels and lymphopenia.

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Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women

Cited by 19 publications

References 40 publications

Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial

Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial

Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

Bone Metabolism Alterations in Patients with Common Variable Immune Deficiency: A Retrospective Cohort Study

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