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

Inflammation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00183001
• Other study ID #: AG0048
• Secondary ID: R01AG019147R01HL
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: February 13, 2009
• Start date: October 2001
• Est. completion date: October 2006

Study information

• Verified date: February 2009
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 452
• Est. completion date: October 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Calcinosis
• Inflammation
• Osteoporosis
• Vascular Calcification

Intervention

Drug:
• Vitamin K

Locations

Country	Name	City	State
United States	Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)	Arthritis Foundation, National Heart, Lung, and Blood Institute (NHLBI), USDA Beltsville Human Nutrition Research Center

Country where clinical trial is conducted

United States, 

References & Publications (4)

Booth SL, Broe KE, Peterson JW, Cheng DM, Dawson-Hughes B, Gundberg CM, Cupples LA, Wilson PW, Kiel DP. Associations between vitamin K biochemical measures and bone mineral density in men and women. J Clin Endocrinol Metab. 2004 Oct;89(10):4904-9. — View Citation

Doherty TM, Asotra K, Fitzpatrick LA, Qiao JH, Wilkin DJ, Detrano RC, Dunstan CR, Shah PK, Rajavashisth TB. Calcification in atherosclerosis: bone biology and chronic inflammation at the arterial crossroads. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11201-6. Epub 2003 Sep 19. — View Citation

Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int. 1996 Nov;59(5):352-6. — View Citation

O'Donnell CJ, Shea MK, Price PA, Gagnon DR, Wilson PW, Larson MG, Kiel DP, Hoffmann U, Ferencik M, Clouse ME, Williamson MK, Cupples LA, Dawson-Hughes B, Booth SL. Matrix Gla protein is associated with risk factors for atherosclerosis but not with coronar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3 year change in bone mineral density at the hip
Primary	3 year change in coronary calcification score
Primary	Hand osteoarthritis score at final visit
Primary	Concentration and attention scores at final visit
Secondary	3 year change in biochemical measures of vitamin K status
Secondary	3 year change in bone turnover
Secondary	3 year change in measures of inflammation
Secondary	Cardiac changes over 3 years
Secondary	Difference in joint symptoms at final visit
Secondary	3 year change in bone mineral density of the heel, spine and total body