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

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00183001

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), Arthritis Foundation (Other), USDA Beltsville Human Nutrition Research Center (U.S. Fed)

452

Enrollment

Location

Duration (Months)

7.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis Vascular Calcification Inflammation	Drug: Vitamin K	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2001

Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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