Effect of 1 Year Vitamin D or D Plus B-vitamins on Bone Markers in Elderly People (KnoVIB)

Study Overview
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Brief Summary
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The standard recommendation to prevent osteoporosis is to supplement low doses of vitamin D and calcium. Hyperhomocysteinemia has been related to increased risk of osteoporosis.

Detailed Description
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The current study aimed at investigating if homocysteine-lowering effect (low doses of B-vitamins) will add any measurable beneficial effect on bone markers when added to the standard recommendations for prevention of osteoporosis.

Official Title
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Effect of 1 Year Vitamin D or D Plus B-vitamins on Bone Markers in Elderly People

Conditions
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Nutritional Supplement Toxicity

Intervention / Treatment
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* Dietary Supplement: Vitamin D and Calcium
* Dietary Supplement: Vitamin D, Calcium, Vitamins B9, B6, B12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age> 50 years, male and female Exclusion Criteria: renal dysfunction, recent stroke or coronary event within the last 3 months, current cancer, antifolate treatment, ileum resection, existing B vitamins supplementation, megaloblastic anemia, osteoporotic patients treated with pharmacological doses of vitamin D or antiosteoporotic drugs. Termination criteria were: indication for a high-dose vitamin B supplementation, coronary or vascular event, or surgical procedures during the study.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vitamin D and Calcium<br>a combination of dietary supplement including all 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate | Dietary Supplement: Vitamin D and Calcium<br>* a combination of dietary supplement including all 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate Arm: Experimental: Vitamin D, Calcium, Vitamins B9, B6, B12 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate plus 0,5mg Folic acid, 50 mg B6, 0,5 mg B12<br>|
| Experimental: Vitamin D, Calcium, Vitamins B9, B6, B12<br>a combination of dietary supplement including all 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate plus 0,5mg Folic acid, 50 mg B6, 0,5 mg B12 | Dietary Supplement: Vitamin D, Calcium, Vitamins B9, B6, B12<br>* a combination of dietary supplement including all 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate plus 0,5mg Folic acid, 50 mg B6, 0,5 mg B12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in bone formation markers | Concentrations of bone formation markers in plasma [OC (ng/ml), BAP (U/L)]: are measured: if all are increased indicate enhanced bone formation | baseline, 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma choline and betaine | plasma choline and betaine (all µmol/L): if both increased indicate saving betaine and choline | baseline and aftter 12 months | 
| Changes in global DNA methylation | global DNA methylation [line 1-methylation (expressed as %)] | baseline and after 12 months | 
| Changes in gene-specific gene methylation | After isolating DNA from whole blood, changes in methylation of targeted genes is studied (expressed as %) | baseline and after 12 months | 
| Changes in TMAO | Plasma concentrations of TMAO ((µmol/L) is measured | baseline and after 6 and 12 months | 
| Changes in phospholipid concentration in plasma | Plasma phospholipids ((µmol/L) are measured | baseline and after 12 months | 
| Changes in concentrations of bone resorption markers | concentrations of bone resorption markers [plasma TRAP5b (U/L), urine DPD (nmol//mmol creatinine)]: if both are increased indicate enhanced bone resorption | baseline, 6 and 12 months | 
| Changes in plasma homocysteine concentrations | changes in plasma homocysteine (µmol/L) between the time points | baseline, 6 and 12 months | 
| Changes in plasma levels of folate | changes in serum and whole blood folate (nmol/L) | baseline, 6 and 12 months |