Bone DensityNCT04573946
VITamin D and OmegA-3 TriaL: Interrelationship of Vitamin D and Vitamin K on Bone (VITAL)
A study testing Omega-3 fatty acids (fish oil) and Vitamin D3 in people with Bone Density and Bone Health, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Vitamin D supplements are widely promoted for bone health. Both vitamin D and vitamin K are important for deposition of calcium in bone, but little is known about the relationship of vitamin K status and bone health. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Bone Density, Bone Health, Fractures
- What is being tested?
- Omega-3 fatty acids (fish oil) and Vitamin D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25,871 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2019to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants in VITAL (NCT 01169259) study who met the following criteria of the parent trial are eligible to participate in this ancillary study:
- be men aged 50 years and older or women aged 55 years and older
- have no history of cardiovascular disease or cancer (excluding non-melanoma skin cancer)
- have none of the following: allergy to soy or fish, hypercalcemia, renal failure or dialysis, severe liver disease, hypo- or hyperparathyroidism, sarcoidosis or other granulomatous diseases, or any other serious illnesses
- consume ≤ 1200 mg/d of calcium for the duration of the trial
- consume ≤ 800 IU of vitamin D for duration of the trial
- refrain from taking fish oil supplements for the duration of the trial
Who cannot join
- For aims 2 and 3, those who are using bisphosphonates currently or within the past 2 years, or other bone-active medications currently or within the past year are not eligible for this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: VITamin D and OmegA-3 TriaL: Interrelationship of Vitamin D and Vitamin K on Bone
Vitamin D supplements are widely promoted for bone health. Both vitamin D and vitamin K are important for deposition of calcium in bone, but little is known about the relationship of vitamin K status and bone health.
Read the detailed description
The goal of VITAL: Interrelationship of Vitamin D and Vitamin K on Bone is to test whether vitamin K status is associated with incident fractures in a case-cohort design or modifies the randomized effects of vitamin D supplementation vs. placebo on 2-year changes in bone density and structure outcomes.
- Conditions
- Bone Density, Bone Health, Fractures
- Being tested
- Vitamin D3 placebo, Fish oil placebo, Omega-3 fatty acids (fish oil), Vitamin D3
- Keywords
- Vitamin D, Vitamin K
- Medical subject headings
- Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3 placeboDietary supplement
Vitamin D placebo
Fish oil placeboDietary supplement
Fish oil placebo
Omega-3 fatty acids (fish oil)Drug
Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Vitamin D3Dietary supplement
Vitamin D3 (cholecalciferol), 2000 IU per day.
Other Names: cholecalciferol
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D placebo + fish oil placebo | Placebo comparator | Not described Receives: Dietary Supplement: Vitamin D3 placebo; Dietary Supplement: Fish oil placebo |
| Vitamin D placebo + fish oil | Active comparator | Not described Receives: Dietary Supplement: Vitamin D3 placebo; Drug: Omega-3 fatty acids (fish oil) |
| Vitamin D + fish oil placebo | Active comparator | Not described Receives: Dietary Supplement: Fish oil placebo; Dietary Supplement: Vitamin D3 |
| Vitamin D + fish oil | Active comparator | Not described Receives: Drug: Omega-3 fatty acids (fish oil); Dietary Supplement: Vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Fractures
The effect of low vitamin K status (with or without vitamin D supplementation) on the number of new total, non-vertebral and hip fractures.
Measured: 2 years
Secondary outcomes (6)
Change in Areal Bone Density
The effect of low vitamin K status (with or without vitamin D supplementation) on changes in areal bone density at the spine and hip between baseline and two years post-randomization.
Measured: 2 years
Change in Volumetric Bone Mineral Density
The effect of low vitamin K status (with or without vitamin D supplementation) on changes in total, trabecular and cortical volumetric bone mineral density (vBMD) between baseline and two years post-randomization.
Measured: 2 years
Change in Cortical Thickness
The effect of low vitamin K status (with or without vitamin D supplementation) on changes in cortical thickness assessed by peripheral quantitative computed tomography (pQCT) between baseline and two years post-randomization.
Measured: 2 years
Change in Bone Strength
The effect of low vitamin K status (with or without vitamin D supplementation) on changes in bone strength measures assessed by peripheral quantitative computed tomography (pQCT) between baseline and two years post-randomization.
Measured: 2 years
Change in Trabecular Bone Score
The effect of low vitamin K status (with or without vitamin D supplementation) on changes in trabecular bone score between baseline and two years post-randomization.
Measured: 2 years
Concentration of Urine Calcium
The effect of low vitamin K status (with or without vitamin D supplementation) on change in urine calcium excretion between baseline and two years post-randomization.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start1 Jul 2019
- Primary completion21 Jul 2023
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Bone DensityStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 25,871 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Meryl LeBoff, Brigham and Women's Hospital
- Investigators
- Meryl S LeBoff, M.D., Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04573946
- Sponsor's protocol ID
- 2012P000560-1
- Other IDs
- 2R01AR059775-06A1, 5R01AR060574-03
- Status last verified
- Apr 2026
- First submitted
- 1 Sep 2020
- Last updated
- 27 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
LeBoff MS, Yue AY, Copeland T, Cook NR, Buring JE, Manson JE. VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2015 Mar;41:259-68. doi: 10.1016/j.cct.2015.01.007. Epub 2015 Jan 24.
PubMed 25623291Donlon CM, LeBoff MS, Chou SH, Cook NR, Copeland T, Buring JE, Bubes V, Kotler G, Manson JE. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture. Contemp Clin Trials. 2018 Apr;67:56-67. doi: 10.1016/j.cct.2018.02.003. Epub 2018 Feb 23.
PubMed 29408561Goldman AL, Donlon CM, Cook NR, Manson JE, Buring JE, Copeland T, Yu CY, LeBoff MS. VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men. Osteoporos Int. 2018 Nov;29(11):2505-2515. doi: 10.1007/s00198-018-4633-3. Epub 2018 Jul 18.
PubMed 30022253LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020 May;35(5):883-893. doi: 10.1002/jbmr.3958. Epub 2020 Jan 30.
PubMed 31923341Chou SH, Booth SL, Cook NR, Kim E, Kotler G, Fu X, Buring JE, Manson JE, LeBoff MS. Investigating the interrelationship of vitamin K and vitamin D status on bone density: results from the VITamin D and OmegA-3 TriaL. JBMR Plus. 2026 Jul 9;10(8):ziag110. doi: 10.1093/jbmrpl/ziag110. eCollection 2026 Aug.
PubMed 42524357
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VITamin D and OmegA-3 TriaL: Interrelationship of Vitamin D and Vitamin K on Bone
- ClinicalTrials.gov ID
- NCT04573946
- Acronym / sponsor ID
- 2012P000560-1
- Conditions
- Bone Density, Bone Health, Fractures
- Keywords
- Vitamin D, Vitamin K
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 25,871 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 21 Jul 2023 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vitamin D supplements are widely promoted for bone health. Both vitamin D and vitamin K are important for deposition of calcium in bone, but little is known about the relationship of vitamin K status and bone health.
Detailed description
The goal of VITAL: Interrelationship of Vitamin D and Vitamin K on Bone is to test whether vitamin K status is associated with incident fractures in a case-cohort design or modifies the randomized effects of vitamin D supplementation vs. placebo on 2-year changes in bone density and structure outcomes.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Vitamin D placebo + fish oil placebo | Placebo comparator | Dietary Supplement: Vitamin D3 placebo, Dietary Supplement: Fish oil placebo |
| Vitamin D placebo + fish oil | Active comparator | Dietary Supplement: Vitamin D3 placebo, Drug: Omega-3 fatty acids (fish oil) |
| Vitamin D + fish oil placebo | Active comparator | Dietary Supplement: Fish oil placebo, Dietary Supplement: Vitamin D3 |
| Vitamin D + fish oil | Active comparator | Drug: Omega-3 fatty acids (fish oil), Dietary Supplement: Vitamin D3 |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participants in VITAL (NCT 01169259) study who met the following criteria of the parent trial are eligible to participate in this ancillary study:
- be men aged 50 years and older or women aged 55 years and older
- have no history of cardiovascular disease or cancer (excluding non-melanoma skin cancer)
- have none of the following: allergy to soy or fish, hypercalcemia, renal failure or dialysis, severe liver disease, hypo- or hyperparathyroidism, sarcoidosis or other granulomatous diseases, or any other serious illnesses
- consume ≤ 1200 mg/d of calcium for the duration of the trial
Key exclusion criteria (1 listed)
- For aims 2 and 3, those who are using bisphosphonates currently or within the past 2 years, or other bone-active medications currently or within the past year are not eligible for this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3 placeboVitamin D placebo | Dietary supplement | Vitamin D placebo + fish oil, Vitamin D placebo + fish oil placebo |
| Fish oil placeboFish oil placebo | Dietary supplement | Vitamin D + fish oil placebo, Vitamin D placebo + fish oil placebo |
| Omega-3 fatty acids (fish oil)Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]). | Drug | Vitamin D + fish oil, Vitamin D placebo + fish oil |
| Vitamin D3Vitamin D3 (cholecalciferol), 2000 IU per day. Other Names: cholecalciferol | Dietary supplement | Vitamin D + fish oil, Vitamin D + fish oil placebo |
Primary outcome
Number of Fractures
Time frame: 2 years
The effect of low vitamin K status (with or without vitamin D supplementation) on the number of new total, non-vertebral and hip fractures.
6 secondary outcomes
Change in Areal Bone Density
Time frame: 2 years
Change in Volumetric Bone Mineral Density
Time frame: 2 years
Change in Cortical Thickness
Time frame: 2 years
Change in Bone Strength
Time frame: 2 years
Change in Trabecular Bone Score
Time frame: 2 years
Concentration of Urine Calcium
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Background: PubMed 25623291LeBoff MS, Yue AY, Copeland T, Cook NR, Buring JE, Manson JE. VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2015 Mar;41:259-68. doi: 10.1016/j.cct.2015.01.007. Epub 2015 Jan 24.
- Background: PubMed 29408561Donlon CM, LeBoff MS, Chou SH, Cook NR, Copeland T, Buring JE, Bubes V, Kotler G, Manson JE. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture. Contemp Clin Trials. 2018 Apr;67:56-67. doi: 10.1016/j.cct.2018.02.003. Epub 2018 Feb 23.
- Background: PubMed 30022253Goldman AL, Donlon CM, Cook NR, Manson JE, Buring JE, Copeland T, Yu CY, LeBoff MS. VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men. Osteoporos Int. 2018 Nov;29(11):2505-2515. doi: 10.1007/s00198-018-4633-3. Epub 2018 Jul 18.
- Background: PubMed 31923341LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020 May;35(5):883-893. doi: 10.1002/jbmr.3958. Epub 2020 Jan 30.
- Derived from this study: PubMed 42524357Chou SH, Booth SL, Cook NR, Kim E, Kotler G, Fu X, Buring JE, Manson JE, LeBoff MS. Investigating the interrelationship of vitamin K and vitamin D status on bone density: results from the VITamin D and OmegA-3 TriaL. JBMR Plus. 2026 Jul 9;10(8):ziag110. doi: 10.1093/jbmrpl/ziag110. eCollection 2026 Aug.
- VITAL Study WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meryl S LeBoff, M.D. principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Omega-3 fatty acids (fish oil) and Vitamin D3 in people with Bone Density and Bone Health, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Fractures (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04573946, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.