Vitamin K Supplementation in Post-Menopausal Osteopenia

Phase 3

Completed

• Conditions: Post-Menopausal Osteoporosis; Post-Menopausal Osteopenia
• Interventions: Dietary Supplement: placebo; Dietary Supplement: vitamin K1 (phylloquinone)

• Registration Number: NCT00150969
• Lead Sponsor: University Health Network, Toronto

Brief Summary

The purpose of this study is to determine whether supplementation with 5 mg vitamin K daily over a 2-year period will prevent bone loss in post-menopausal women with osteopenia.

Detailed Description

Osteoporosis is major cause of morbidity and mortality in Canadian postmenopausal women. It is a systemic disease characterized by low bone mass and deterioration of bone microarchitecture, resulting in bone fragility and an increased risk of fractures. One in six women over the age of 50 have osteoporosis. The lifetime risk of an osteoporotic fracture for an average 50 year-old Canadian woman is \>40%. The annual health care costs for osteoporotic fractures in Canada have been estimated to exceed $1.3 billion.

Recent data suggest that vitamin K supplements may decrease bone loss and prevent fractures. Vitamin K is a co-factor of gamma-glutamyl carboxylase, an enzyme that catalyzes the gamma-carboxylation of glutamic acid residues in bone matrix proteins such as osteocalcin. Vitamin K has been reported to enhance bone formation in both in vitro studies and in vivo studies in animals. Vitamin K levels are low in individuals with osteoporosis and in patients with osteoporotic fractures. The few studies examining vitamin K supplementation in humans have showed promising results with no significant side effects, but these studies had significant methodological shortcomings such as inadequate sample size and lack of randomization.

The primary objective of our study is to examine whether vitamin K supplementation will increase bone mineral density in postmenopausal women with osteopenia. Our secondary objectives are to examine the possible adverse effects from long-term vitamin K supplementation, to investigate whether vitamin K will decrease risk of fractures and to determine if vitamin K affects quality of life. Our hypotheses are that vitamin K increases bone mineral density in postmenopausal women, and that there are no significant adverse effects from vitamin K supplementation.

Study Timeline

• Study Start: 2002-01
• Study First Submitted: 2005-09-06
• Study First Submitted QC: 2005-09-06
• Study First Posted: 2005-09-08
• Primary Completion: 2006-09
• Study Completion: 2007-09
• Results First Submitted: 2012-01-10
• Results First Submitted QC: 2012-02-23
• Results First Posted: 2012-03-26
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-04
• Last Update Posted: 2023-12-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 440

Inclusion Criteria

Postmenopausal: One year since the natural cessation of menses, or Hysterectomy with either postmenopausal status confirmed by FSH lab values, or age 55 and above AND 2. Osteopenic: T-score at baseline has to be between (and including) -1.0 and

-2.0 in the lumbar spine (L1-L4), total hip or femoral neck, and the lowest reading of the above three measurements must be between -1.0 and -2.0

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Exclusion Criteria

1. Women ever having had a fragility fracture after age 40;
2. Women currently on anticoagulants, previously on anticoagulants in the past 3 months, or expected to be on anticoagulants in the near future;
3. Women on hormone replacement therapy, raloxifene, bisphosphonates or calcitonin during the past 3 months;
4. Women who have ever been on a bisphosphonate for more than 6 months;
5. Women previously diagnosed with Paget's disease, hyperparathyroidism, hyperthyroidism or other metabolic bone diseases;
6. Women with decompensated diseases of the liver, kidney, pancreas, lung, or heart;
7. Women with a history of active cancer in the past 5 years;
8. Women taking mega-doses of vitamin A (more than 10,000 iu per day) or E (more than 400 iu per day);
9. Women involved in other clinical trials;
10. Any women who, in the opinion of the principal investigator, is at poor medical or psychiatric risk for the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	-
phyloquinone	vitamin K1 (phylloquinone)	5 mg Vitamin K1

Primary Outcome Measures

Name	Time	Method
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.	0 to 24 months	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.	0 to 24 months	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Secondary Outcome Measures

Name	Time	Method
Difference in Number of New Cancers by Treatment Arm.	up to 48 months
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.	0 to 48 months	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin	0 to 24 months	measured by osteocalcin hydroxyapatite binding assay
Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX)	0-24 months	measured by CTX Elisa assay on elecsys platform
Difference in Number of New Clinical Fractures by Treatment Arm.	up to 48 months	these included fragility fractures
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.	0 to 48 months	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.	0 to 48 months	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker	0-24 months	measured by osteocalcin on elecsys platform
Difference in Serious Adverse Events	up to 48 months	These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.	0 to 48 months	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Trial Locations

Locations (5)

St. Michael's Hospital Health Centre; 🇨🇦 Toronto, Ontario, Canada

University Health Network, Osteoporosis Department; 🇨🇦 Toronto, Ontario, Canada

Sunnybrook & Women's College Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Mt. Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

University of Toronto; 🇨🇦 Toronto, Ontario, Canada