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

National Heart, Lung, and Blood Institute (NHLBI), Arthritis Foundation, USDA Beltsville Human Nutrition Research Center

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.

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.

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

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