Effect of Vitamin K on Age-Related Bone Loss and Vascular Calcification

Study Overview
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Brief Summary
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The purpose of this study is to determine if supplemental vitamin K will reduce age-related bone loss in elderly men and women above that achieved by supplementation.

Detailed Description
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This is a three-year, double-blind, placebo-controlled trial to study the effect of vitamin K supplementation (500 µg/d) on bone density at the hip, markers of bone turnover, vascular calcification, osteoarthritis and tests of concentration in 452 men and women, aged 60-80 years. All participants will also be receiving calcium and vitamin D supplements, in addition to a multivitamin, to prevent any potential bone loss associated with dietary inadequacy of these nutrients. Measurements of plasma vitamin K concentrations, percent undercarboxylated osteocalcin (markers of vitamin K status), serum osteocalcin, collagen Type-I-crosslink N-telopeptides (markers of bone turnover) and BMD of the hip, as well as the heel, spine and total body at 0, 6, 12, 24, and 36 months of vitamin K supplementation. Vascular calcification will be measured at baseline and at 36 months of vitamin K supplementation by multi-slice CT scan. An additional EKG will be performed at 36 months of vitamin K supplementation to determine cardiac changes that may have occurred over the course of the study. Bilateral hand x-rays will be measured at 36 months of vitamin K supplementation, as will the administration of the Framingham OA questionnaire. Plasma 25-hydroxyvitamin D concentrations and urinary calcium and sodium will be measured at the same time points to be used as covariates in this assessment. In addition, 1,25-dihydroxyvitamin D will be measured at the beginning and end of the study. Other covariates collected throughout the study include age, weight, anthropometric data, physical activity, medication used, smoking, plasma lipids, insulin and measures of inflammation, B vitamins and dietary intakes. In addition, two tests of attention and concentration will be administered at 36 months of vitamin K supplementation. This trial will determine if supplemental vitamin K will reduce age-related bone loss, vascular calcification, osteoarthritis and concentration in elderly men and women, above that achieved by supplemental calcium and vitamin D alone.

Official Title
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Effect of Vitamin K on Age-Related Bone Loss and Vascular Calcification

Conditions
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Osteoporosis, Vascular Calcification, Inflammation

Intervention / Treatment
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* Drug: Vitamin K


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory general population Dietary intake of vitamin K below 120 mcg Exclusion Criteria: Unable to give informed consent Usual dietary intake of phylloquinone greater than 120 µg/d Usual dietary calcium intake greater than 1500 mg/d Usual dietary vitamin D intake greater than 1500 IU Women less than 5 years postmenopausal Femoral neck BMD (bone mineral density) at screening that is greater than 1.8 SD above or below an age-matched reference mean 24-hour calcium to creatinine ratio exceeding 300 mg/g for women or 350 mg/g for men Terminal illness Renal or liver disease requiring treatment Kidney stone in the past 5 years Current hyperparathyroidism Bilateral hip surgery Treatment with a bisphosphonate, calcitonin, estrogen progestin, androgen, tamoxifen, or fluoride (other than dental rinse), or any other treatment for osteoporosis in previous 3 months Warfarin or anticoagulant use in the past 12 months Nonambulation Known coronary disease, defined by myocardial infarction or unstable angina Prior open heart surgery Atrial fibrillation

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Vitamin K|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year change in bone mineral density at the hip |  |  | 
| 3 year change in coronary calcification score |  |  | 
| Hand osteoarthritis score at final visit |  |  | 
| Concentration and attention scores at final visit |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year change in biochemical measures of vitamin K status |  |  | 
| 3 year change in bone turnover |  |  | 
| 3 year change in measures of inflammation |  |  | 
| Cardiac changes over 3 years |  |  | 
| Difference in joint symptoms at final visit |  |  | 
| 3 year change in bone mineral density of the heel, spine and total body |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin therapy, nutritional supplement, dietary supplement, Vitamin K deficiency, bone density