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Association Between Vitamin D Receptor Polymorphism and Serum Vitamin D Levels in Children With Low-Energy Fractures

Sponsor
Medical University of Bialystok (Other)
Overall Status
Completed
CT.gov ID
NCT02805647
Collaborator
American Medical Holdings Inc., Staten Island, NY 10314 USA (Other), School of Pharmacy, Creighton University, Omaha, NE 68178 USA (Other)
222
Enrollment
1
Location
60
Duration (Months)
3.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study was designed to determine the impact of vitamin D serum levels and vitamin D receptor (VDR) polymorphisms on the occurrence of low energy fractures in children.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    The study group consisted of 100 children aged 3 to 18 years (78% boys) hospitalized in the Department of Pediatric Orthopedics in 2011-2013 due to low-energy fractures. The control group (122 children, 68% boys) consisted of children aged 3 to 17 years, hospitalized for other reasons (injuries, diagnosis of knee ligament injuries and others) without fractures. Children with osteogenesis imperfecta (OI) were excluded from the study. From each patient and their parent/guardian a written informed consent to participate in the study was obtained. Low-energy fracture was defined as a fracture sustained from a fall from the patient's own height or a fall during team games. All fractures were radiologically confirmed.

    During hospitalization the patients and their parents completed a questionnaire on demographic data, the place of residence (urban/rural), earlier fractures and physical activity. The degree of sexual maturity was assessed using a survey of puberty development on the basis of Puberty Development Scale [20-22]. The patients' body weights and heights were measured, and the Cole indicator was calculated to assess the nutritional status of the patients.

    Serum concentrations of total vitamin D [25-hydroxy vitamin D3 ((25(OH)D3)) plus 25-hydroxy vitamin D2 ((25(OH)D2))] in the plasma of all the children were determined by electrochemiluminescence using paramagnetic particles coated with streptavidin and ruthenium compound on the Cobas e 411 apparatus by Roche. According to our laboratory, the reference value range for total vitamin D was 30.0 - 74.0 ng/ml.Whole blood samples were collected in tubes containing EDTA and stored at -20°C. DNA was isolated using the MasterPureTM DNA Purification Kit (Akor Laboratories) and quantified on a spectrophotometer (Nanodrop 2000, Thermo Scientific). The genotypes for four restriction fragment length polymorphisms of the vitamin D receptor (VDR) gene were determined by standard polymerase chain reaction (PCR) techniques and enzymatic digestion of the products with FokI, ApaI, TaqI and BsmI (Thermo Scientific). In short, PCR were performed in a final volume of 20 µl containing 50-100 ng DNA, 0.3 µM of each primer and JumpStartTM REDTaqTM ReadyMixTM (Sigma). After initial denaturation for 3 min at 94 °C, samples were subjected to 35 cycles of amplification, consisting of a 30-sec denaturing phase at 94 °C, a 30-sec annealing phase (FokI at 60 °C, ApaI and TaqI at 70 °C, BsmI at 62 °C), a 30-s extension phase at 72 °C, and 4-min at 72 °C on a Bio-Rad thermal cycler CFX96TM. The primers used for FokI polymorphism were: forward 5'-AGC TGG CCC TGG CAC TGA CTC TGC TCT-3', reverse 5'-ATG GAA ACA CCT TGC TTC TTC TCC CTC-3'; ApaI and TaqI: forward 5'-CAG AGC ATG GAC AGG GAG CAA-3', reverse 5'-GCA ACT CCT CAT GGC TGA GGT CTC-3' and BsmI: forward 5'-AGT GTG CAG GCG ATT CGT AG-3', reverse 5'-ATA GGC AGA ACC ATC TCT CAG-3' [25]. The PCR products were digested according to the manufacturer's instructions and separated on 2% agarose gel. The polymorphisms were documented by photographing under UV illumination using G:Box (Syngene). A random subset (20% of samples) was repeated to verify the results. Upper case letters "F", "A", "T" and "B" indicate the absence of the cut site for FokI, ApaI, TaqI and BsmI polymorphisms, respectively, whereas lower case letters "f", "a", "t", and "b" indicate its presence.To examine the relationships between quality attributes Chi-square test of independence and Fisher's exact test were used. The normality of distribution was verified using the Kolmogorov-Smirnov test with the Lilliefors significance correction and the Shapiro-Wilk test. There was no normal distribution of quantitative variables analyzed. To compare the quantitative variables without normal distribution a nonparametric Mann - Whitney U test was used. Models of uni-variate and multi-variate linear regression and logistic regression were established. Results were considered statistically significant at p <0.05. The calculations were performed using Statistica 10.0 by StatSoft, IBM SPSS Statistics 21.0 by Predictive Solutions Company and Stata / IC 13.1 packages by StataCorp LP

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    222 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Prospective
    Official Title:
    Association Between Vitamin D Receptor Polymorphism and Serum Vitamin D Levels in Children With Low-Energy Fractures
    Study Start Date :
    Jan 1, 2011
    Actual Primary Completion Date :
    Dec 1, 2013
    Actual Study Completion Date :
    Jan 1, 2016

    Arms and Interventions

    Arm Intervention/Treatment
    Fracture/study group

    The study group consisted of 100 children aged 3 to 18 years (78% boys) hospitalized in the Department of Pediatric Orthopedics in 2011-2013 due to low-energy fractures
    Control group

    The control group (122 children, 68% boys) consisted of children aged 3 to 17 years, hospitalized for other reasons (injuries, diagnosis of knee ligament injuries and others) without fractures

    Outcome Measures

    Primary Outcome Measures

    1. Vitamin D Status; VDR Status [We measured Vitamin D status at the time of admission - at the time of fracture]

      Serum concentrations of total vitamin D; VDR polymorphism test

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • low-energy fractures.

    • healthy children hospitalized for other reasons than fractures (injuries, diagnosis of knee ligament injuries and others) without fractures

    Exclusion Criteria:
    • Children with osteogenesis imperfecta (OI) were excluded from the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Pediatric Orthopedics and Traumatology Medical University of Bialystok Bialystok Poland 15-274

    Sponsors and Collaborators

    • Medical University of Bialystok
    • American Medical Holdings Inc., Staten Island, NY 10314 USA
    • School of Pharmacy, Creighton University, Omaha, NE 68178 USA

    Investigators

    • Principal Investigator: Michał Karpiński, MD, Department of Pediatric Orthopedics and Traumatology Medical University of Bialystok

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Michal Karpinski, MD, Medical University of Bialystok
    ClinicalTrials.gov Identifier:
    NCT02805647
    Other Study ID Numbers:
    • MUBialystok
    First Posted:
    Jun 20, 2016
    Last Update Posted:
    Dec 4, 2019
    Last Verified:
    Nov 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Michal Karpinski, MD, Medical University of Bialystok
    25-Hydroxy-vitamin D, children, bone fractures, vitamin D receptor polymorphism
    Additional relevant MeSH terms:
    Fractures, Bone

    Study Results

    Participant Flow

    Recruitment Details Children with low energy fractures
    Pre-assignment Detail without bone diseases such as OI
    Arm/Group Title Fracture/Study Group Control Group
    Arm/Group Description The study group consisted of 100 children aged 3 to 18 years (78% boys) hospitalized in the Department of Pediatric Orthopedics in 2011-2013 due to low-energy fractures The control group (122 children, 68% boys) consisted of children aged 3 to 17 years, hospitalized for other reasons (injuries, diagnosis of knee ligament injuries and others) without fractures
    Period Title: Overall Study
    STARTED 100 122
    COMPLETED 100 122
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Fracture/Study Group Control Group Total
    Arm/Group Description The study group consisted of 100 children aged 3 to 18 years (78% boys) hospitalized in the Department of Pediatric Orthopedics in 2011-2013 due to low-energy fractures The control group (122 children, 68% boys) consisted of children aged 3 to 17 years, hospitalized for other reasons (injuries, diagnosis of knee ligament injuries and others) without fractures Total of all reporting groups
    Overall Participants 100 122 222
    Age (Count of Participants)
    <=18 years
    100
    100%
    122
    100%
    222
    100%
    Between 18 and 65 years
    0
    0%
    0
    0%
    0
    0%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Median (Standard Deviation) ]
    Median (Standard Deviation) [years]
    13
    (2)
    13
    (2)
    13
    (2)
    Sex: Female, Male (Count of Participants)
    Female
    22
    22%
    39
    32%
    61
    27.5%
    Male
    78
    78%
    83
    68%
    161
    72.5%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    Poland
    100
    100%
    122
    100%
    222
    100%
    Total vitamin D [25(OH)D3 plus 25(OH)D2] serum concentrations were evaluated in every patient. Genot (ng/ml) [Median (Standard Deviation) ]
    Median (Standard Deviation) [ng/ml]
    13.81
    (12)
    17.49
    (16)
    15
    (14)

    Outcome Measures

    1. Primary Outcome
    Title Vitamin D Status; VDR Status
    Description Serum concentrations of total vitamin D; VDR polymorphism test
    Time Frame We measured Vitamin D status at the time of admission - at the time of fracture

    Outcome Measure Data

    Analysis Population Description
    Children from Poland Podlasie region
    Arm/Group Title Fracture/Study Group Control Group
    Arm/Group Description The study group consisted of 100 children aged 3 to 18 years (78% boys) hospitalized in the Department of Pediatric Orthopedics in 2011-2013 due to low-energy fractures The control group (122 children, 68% boys) consisted of children aged 3 to 17 years, hospitalized for other reasons (injuries, diagnosis of knee ligament injuries and others) without fractures
    Measure Participants 100 122
    Mean (Inter-Quartile Range) [ng/ml]
    13.81
    17.49

    Adverse Events

    Time Frame We measured vitamin D status and VDR polymporphism at admission to hospital and when patients were enrolled to the study
    Adverse Event Reporting Description
    Arm/Group Title Fracture/Study Group Control Group
    Arm/Group Description The study group consisted of 100 children aged 3 to 18 years (78% boys) hospitalized in the Department of Pediatric Orthopedics in 2011-2013 due to low-energy fractures The control group (122 children, 68% boys) consisted of children aged 3 to 17 years, hospitalized for other reasons (injuries, diagnosis of knee ligament injuries and others) without fractures
    All Cause Mortality
    Fracture/Study Group Control Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Fracture/Study Group Control Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/100 (0%) 0/122 (0%)
    Other (Not Including Serious) Adverse Events
    Fracture/Study Group Control Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/100 (0%) 0/122 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title MichałKarpiński
    Organization Department of Pediatric Orthopedics and Traumatology Medical University of Bialystok
    Phone 692224714 ext +48
    Email gufkarp@gmail.com
    Responsible Party:
    Michal Karpinski, MD, Medical University of Bialystok
    ClinicalTrials.gov Identifier:
    NCT02805647
    Other Study ID Numbers:
    • MUBialystok
    First Posted:
    Jun 20, 2016
    Last Update Posted:
    Dec 4, 2019
    Last Verified:
    Nov 1, 2019