The Vitamin K2 and D3 Intervention Trial in Children and Adolescents With the Low-energy Fractures

Study Overview
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Brief Summary
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a prospective, three- month, randomized, double-blind, placebo-controlled, intervention trial (RDBPC), investigating the effect of vitamin K2 (menaquinone-7) and vitamin D3 on the healing process of low-energy bone fractures in children and adolescents

Detailed Description
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At the admission of patients to the orthopedic outpatient clinic, presence of low- energy fractures will be established based on the anamnesis, physical examination and radiological evaluation. Tests to obtain the baseline blood levels of vitamin D3 will be performed, and only children with vitamin D3 levels lower than 30ng/ml in the blood will be included in the study. The selected population will then be randomly assigned by an independent investigator to the three study groups, receiving daily for three months identical- looking soft gel capsules (1 capsule/patient/day) containing supplements of vitamin D3 2,000 IU, 90 mcg of vitamin K2 as menaquinone-7 combined with 2,000 IU D3, and olive oil-containing placebo capsules respectively. During the 3-month follow-up visits to the outpatient orthopedic clinic, the pediatric orthopedist will examine the patient, evaluate the X-ray, and determine the progress in bone union and the range of joint motion. The patients will visit the clinic on weeks 1,2,4,6,8, and 12. The compliance taking the supplements will be assessed by registering a pill count returned by a patient during the scheduled visit. The blood samples will be collected upon admission to the study, day 0, and after the 3-month regimen. The blood samples will be collected for evaluation of bone turnover markers and the status of vitamin K and vitamin D3. The primary evaluation endpoints will include: the dynamics of fracture healing, changes in levels of osteocalcin, and vitamin K and vitamin D3 levels against the placebo group. The bone fracture healing milestones will be based on bone union defined as the absence of pain and the presence of bridging callus in three of the four cortices seen on the front rear projection and lateral radiographic views of the bone. Delayed union is defined as incomplete consolidation at 90 Days

Official Title
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Rationale and Design of the Vitamin K2 and Vitamin D3 Intervention Trial in Children and Adolescents With the Low-energy Bone Fractures

Conditions
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Fracture Healing, Vitamin D3, Deficiency of Vitamin K2

Intervention / Treatment
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* Dietary Supplement: Vitamin D and K2 supplementation
* Dietary Supplement: Vitamin D supplementation
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 18 years Presence of low-energy fracture Vitamin D serum level <30ng/ml Exclusion Criteria: Age > 18 years Lack of low-energy bone fracture Oral anticoagulants treatments, which interfere with vitamin K cycle Current supplementation with vitamin vitamins K2 or vitamin D3 Osteogenesis imperfecta and other bone diseases Vitamin D concentration > 30ng/ml

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a prospective, three- month, randomized, double-blind, placebo-controlled, intervention trial (RDBPC),
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D group<br>vitamin D supplementation - time to fracture healing | Dietary Supplement: Vitamin D supplementation<br>* if supplementation of vitamin D alone changes the time to fracture healing<br>|
| Active Comparator: Vitamin D and K2 group<br>Vitamin D and K 2 supplementation - time of fracture healing | Dietary Supplement: Vitamin D and K2 supplementation<br>* if supplementation of vitamin D and K2 changes the time to fracture healing<br>|
| Placebo Comparator: Placebo group<br>Placebo - time to fracture healing | Dietary Supplement: Placebo<br>* Placebo control group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to bone union | The bone fracture healing milestones will be based on bone union defined as the absence of pain and the presence of bridging callus in three of the four cortices seen on the AnteroPosteral and lateral radiographs | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D concentration changes | changes in vitamin D serum concentration | 3 months | 
| Vitamin K2 concentration changes | changes in vitamin K2 serum concentration | 3 months | 
| Changes in bone markers concentration | Changes in bone-specific alkaline phosphatase (BALP), N-terminal telopeptide (NTX) | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, vitamin K2, low-energy fractures, fracture healing, children