Fracture
Conditions
Keywords
Tibial Shaft, Tibia, Femoral Shaft, Femur, Vitamin D, Fracture Healing
Brief summary
The objective is to determine the effect of vitamin D3 supplementation on fracture healing at 3 months.
Detailed description
Vitamin D supplements are increasingly being recommended to healthy adult fracture patients without an osteoporotic injury. Although this is a relatively new practice pattern, the basis for this adjunct therapy is grounded in the high hypovitaminosis D prevalence rates (up to 75%) among healthy adult fracture patients, and the strong biologic rationale for the role of vitamin D in fracture healing. Briefly, experimental animal studies have demonstrated that the concentration of vitamin D metabolites is higher at a fracture callus compared to the uninjured contralateral bone, vitamin D supplementation leads to decreased time to union and increased callus vascularity, and increases mechanical bone strength compared to controls. While evidence to confirm that vitamin D supplementation improves fracture healing in clinical studies does not exist, the pre-clinical data are compelling and worthy of further investigation. With modern orthopaedic surgical care, rates of complications following tibia and femoral shaft fractures can be as high as 15%. Complications, including delayed union, nonunion, or infection often require secondary surgical procedures and result in profound personal and societal economic costs. While surgeons continue to seek advances in surgical technique, it is becoming increasingly obvious that innovations in orthopaedic techniques or implants are unlikely to eliminate complications. As a result, considerable attention is currently focused on adjunct biologic therapies, such as vitamin D. A recent survey of 397 orthopaedic surgeons showed that only 26% routinely prescribe vitamin D supplementation to adult fracture patients. Of the 93 surgeons who indicated that they routinely prescribe vitamin D supplementation, 29 different dosing regimens were described ranging from low daily doses of 400 IU to loading doses of 600,000 IU. This suggests a high level of clinical uncertainty surrounding the use and optimal dose of vitamin D supplementation in adult fracture patients. If vitamin D supplementation improves fracture healing outcomes, then there is a large opportunity to increase its use; however, before widespread adoption occurs, research is needed to optimize the dosing strategy, establish the dosing safety in the immobilized fracture healing population, and overcome potential medication adherence issues among the often marginalized patients that suffer trauma. The long-term goal of our research program is to conduct a large phase III RCT to determine which dose of vitamin D3 supplementation optimally improves acute fracture healing outcomes in healthy adult patients (18-50 years). The current proposed phase II exploratory trial will perform important preliminary work to test the central hypothesis that vitamin D3 dose and timing of administration is critical for improving fracture healing at 3 months. This trial will also inform the feasibility of the large phase III RCT.
Interventions
DRUGVitamin D3
OTHERPlacebo
Sponsors
McMaster University
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Adult men or women ages 18-50 years 2. Closed or low grade open (Gustilo type I or II) tibial or femoral shaft fracture 3. Fracture treated with a reamed, locked, intramedullary nail 4. Acute fracture (enrolled within 7 days of injury) 5. Provision of informed consent.
Exclusion criteria
1. Osteoporosis 2. Stress fractures 3. Elevated serum calcium (\>10.5 mg/dL) 4. Atypical femur fractures as defined by American Society for Bone and Mineral Research (ASBMR) criteria 5. Pathological fractures secondary to neoplasm or other bone lesion 6. Patients with known or likely undiagnosed disorders of bone metabolism such as Paget's disease, osteomalacia, osteopetrosis, osteogenesis imperfecta etc. 7. Patients with hyperhomocysteinemia 8. Patients with an allergy to vitamin D or another contraindication to being prescribed vitamin D 9. Patients currently taking an over the counter multivitamin that contains vitamin D and are unable or unwilling to discontinue its use for this study 10. Patients who will likely have problems, in the judgment of the investigators, with maintaining follow-up 11. Pregnancy 12. Patients who are incarcerated 13. Patients who are not expected to survive their injuries 14. Other lower extremity injuries that prevent bilateral full weight-bearing by 6 weeks post-fracture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT) | 3 months post-injury | FIX-IT is a standardized measure of weight-bearing and pain in patients with lower extremity fractures, specifically tibia and femur fractures. The FIX-IT score ranges from 0 to 12 points in 2 domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points) The ability to bear weight is assessed through the single-leg stand and ambulation procedures. Pain is assessed through palpation and stress procedures. The scores in both domains, which are weighted equally, are summed to obtain the final total score; the maximum score of 12 indicates the highest level of function. |
| Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST) | 3 months post-injury | Radiographic fracture healing was measured using the Radiographic Union Score for Tibial fractures (RUST), which assesses the presence of bridging callus or a persistent fracture line on each of four cortices. This method evaluates two orthogonal radiographic views; each cortex is attributed points ranging from 1 to 3. A fracture in the immediate postoperative period will receive the minimum score, 4, (1 point for each of the four cortices) and a fully consolidated or healed fracture will be assigned the maximum score, 12 (3 points on each of the four cortices). |
| Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX) | 3 months post-injury | The BTM C-terminal telopeptide of type I collagen (CTX). CTX is a marker of bone resorption. Clinically important changes in the CTX markers are unknown; however, in a previous study of tibia fracture healing, Veitch et al observed concentrations of both bone turnover markers approximately 100% greater than baseline values.43 Given the large changes observed in these bone turnover markers, the same criteria will be applied for identifying a potentially clinically beneficial regimen and remain powered to detect a mean difference of 20% (SD 30%). |
| Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP) | 3 months post-injury | P1NP is a bone-formation marker and prior research has found that it is highest at 12 weeks after fractures of the tibial shaft and proximal femur. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of Parathyroid Hormone | Up to 3 months post-injury | Helps the body to maintain stable levels of calcium in the blood |
| Serum Level of 25(OH)D | Up to 3 months post-injury | Correlations will be assessed between participants' 25(OH)D levels at enrolment, changes in 25(OH)D levels from enrolment to 3 months, and 25(OH)D levels at 3 months and fracture healing |
| Count of Participants Who Completed Radiographic Imaging Measures | up to 12 months | Count of participants who completed radiographic imaging measures to determine participant protocol adherence and assists with identifying healing status |
| Count of Participants Who Completed Blood Measures | Up to 3 months post-injury | Will measure participants adherence to the blood measures of the protocol. |
| Number of Participants With Adherence With Vitamin D Supplementation | Up to 3 months post-injury | Will measure adherence with vitamin D supplementation based on participants self report at the 6 week and 3 month visits. |
| Number of Participants With Adverse Events (AE) | Up to 12 months post-injury | A count of the participants who experienced adverse events will measure participant safety |
| Serum Levels of Calcium | Up to 3 months post-injury | Will measure participant safety |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Loading Dose 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months.
Vitamin D3
Placebo | 27 |
| High Daily Dose Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months.
Vitamin D3
Placebo | 24 |
| Low Daily Dose Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months.
Vitamin D3
Placebo | 24 |
| Control Group Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months.
Placebo | 27 |
| Total | 102 |
Baseline characteristics
| Characteristic | High Loading Dose | High Daily Dose | Low Daily Dose | Control Group | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 24 Participants | 24 Participants | 27 Participants | 102 Participants |
| Age, Continuous | 27.4 years STANDARD_DEVIATION 8.1 | 28.8 years STANDARD_DEVIATION 7.3 | 31.1 years STANDARD_DEVIATION 9.8 | 31.3 years STANDARD_DEVIATION 7.9 | 29.65 years STANDARD_DEVIATION 8.28 |
| Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA AO/OTA Class 32.A | 10 Participants | 6 Participants | 9 Participants | 9 Participants | 34 Participants |
| Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA AO/OTA Class 32.B | 4 Participants | 4 Participants | 5 Participants | 3 Participants | 16 Participants |
| Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA AO/OTA Class 32.C | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 12 Participants |
| Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA AO/OTA Class 42.A | 7 Participants | 3 Participants | 3 Participants | 6 Participants | 19 Participants |
| Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA AO/OTA Class 42.B | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 13 Participants |
| Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA AO/OTA Class 42.C | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 22 Participants | 24 Participants | 26 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fractured bone (Tibia) | 11 Participants | 9 Participants | 10 Participants | 11 Participants | 41 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 11 Participants | 10 Participants | 15 Participants | 47 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 11 Participants | 13 Participants | 10 Participants | 48 Participants |
| Region of Enrollment United States | 27 participants | 24 participants | 24 participants | 27 participants | 102 participants |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 8 Participants | 6 Participants | 32 Participants |
| Sex: Female, Male Male | 14 Participants | 19 Participants | 16 Participants | 21 Participants | 70 Participants |
| Smoking status Current Smoker | 10 Participants | 6 Participants | 7 Participants | 14 Participants | 37 Participants |
| Smoking status Non-Smoker | 16 Participants | 15 Participants | 15 Participants | 13 Participants | 59 Participants |
| Smoking status Previous Smoker | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 6 Participants |
| Vitamin D3 deficient (25(OH)D Serum Levels ,20 ng/mL) | 16 Participants | 11 Participants | 12 Participants | 17 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 24 | 0 / 24 | 0 / 27 |
| other Total, other adverse events | 9 / 27 | 10 / 24 | 11 / 24 | 14 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 24 | 0 / 24 | 0 / 27 |
Outcome results
Primary
Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX)
The BTM C-terminal telopeptide of type I collagen (CTX). CTX is a marker of bone resorption. Clinically important changes in the CTX markers are unknown; however, in a previous study of tibia fracture healing, Veitch et al observed concentrations of both bone turnover markers approximately 100% greater than baseline values.43 Given the large changes observed in these bone turnover markers, the same criteria will be applied for identifying a potentially clinically beneficial regimen and remain powered to detect a mean difference of 20% (SD 30%).
Time frame: 3 months post-injury
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Loading Dose | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX) | 0.59 ng/mL | Standard Deviation 0.75 |
| High Daily Dose | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX) | 0.79 ng/mL | Standard Deviation 0.93 |
| Low Daily Dose | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX) | 0.67 ng/mL | Standard Deviation 0.64 |
| Control Group | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX) | 0.78 ng/mL | Standard Deviation 0.97 |
Primary
Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP)
P1NP is a bone-formation marker and prior research has found that it is highest at 12 weeks after fractures of the tibial shaft and proximal femur.
Time frame: 3 months post-injury
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Loading Dose | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP) | 160.9 ng/mL | Standard Deviation 140.1 |
| High Daily Dose | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP) | 187.8 ng/mL | Standard Deviation 129.3 |
| Low Daily Dose | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP) | 166.7 ng/mL | Standard Deviation 115.8 |
| Control Group | Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP) | 140.7 ng/mL | Standard Deviation 124.7 |
Primary
Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT)
FIX-IT is a standardized measure of weight-bearing and pain in patients with lower extremity fractures, specifically tibia and femur fractures. The FIX-IT score ranges from 0 to 12 points in 2 domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points) The ability to bear weight is assessed through the single-leg stand and ambulation procedures. Pain is assessed through palpation and stress procedures. The scores in both domains, which are weighted equally, are summed to obtain the final total score; the maximum score of 12 indicates the highest level of function.
Time frame: 3 months post-injury
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Loading Dose | Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT) | 10.1 scores on a scale | Standard Deviation 2.5 |
| High Daily Dose | Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT) | 9.7 scores on a scale | Standard Deviation 2.8 |
| Low Daily Dose | Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT) | 9.3 scores on a scale | Standard Deviation 3.3 |
| Control Group | Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT) | 9.0 scores on a scale | Standard Deviation 2.9 |
Primary
Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST)
Radiographic fracture healing was measured using the Radiographic Union Score for Tibial fractures (RUST), which assesses the presence of bridging callus or a persistent fracture line on each of four cortices. This method evaluates two orthogonal radiographic views; each cortex is attributed points ranging from 1 to 3. A fracture in the immediate postoperative period will receive the minimum score, 4, (1 point for each of the four cortices) and a fully consolidated or healed fracture will be assigned the maximum score, 12 (3 points on each of the four cortices).
Time frame: 3 months post-injury
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Loading Dose | Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST) | 11.0 Score on a scale 4-12 | Standard Deviation 2.8 |
| High Daily Dose | Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST) | 11.3 Score on a scale 4-12 | Standard Deviation 2.9 |
| Low Daily Dose | Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST) | 11.0 Score on a scale 4-12 | Standard Deviation 3 |
| Control Group | Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST) | 10.4 Score on a scale 4-12 | Standard Deviation 2.5 |
Secondary
Count of Participants Who Completed Blood Measures
Will measure participants adherence to the blood measures of the protocol.
Time frame: Up to 3 months post-injury
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Loading Dose | Count of Participants Who Completed Blood Measures | baseline | 26 Participants |
| High Loading Dose | Count of Participants Who Completed Blood Measures | Month 3 | 19 Participants |
| High Loading Dose | Count of Participants Who Completed Blood Measures | Week 6 | 21 Participants |
| High Daily Dose | Count of Participants Who Completed Blood Measures | baseline | 24 Participants |
| High Daily Dose | Count of Participants Who Completed Blood Measures | Month 3 | 11 Participants |
| High Daily Dose | Count of Participants Who Completed Blood Measures | Week 6 | 20 Participants |
| Low Daily Dose | Count of Participants Who Completed Blood Measures | Week 6 | 15 Participants |
| Low Daily Dose | Count of Participants Who Completed Blood Measures | baseline | 24 Participants |
| Low Daily Dose | Count of Participants Who Completed Blood Measures | Month 3 | 17 Participants |
| Control Group | Count of Participants Who Completed Blood Measures | baseline | 26 Participants |
| Control Group | Count of Participants Who Completed Blood Measures | Month 3 | 15 Participants |
| Control Group | Count of Participants Who Completed Blood Measures | Week 6 | 22 Participants |
Secondary
Count of Participants Who Completed Radiographic Imaging Measures
Count of participants who completed radiographic imaging measures to determine participant protocol adherence and assists with identifying healing status
Time frame: up to 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Loading Dose | Count of Participants Who Completed Radiographic Imaging Measures | Baseline | 27 Participants |
| High Loading Dose | Count of Participants Who Completed Radiographic Imaging Measures | Week 6 | 24 Participants |
| High Loading Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 3 | 21 Participants |
| High Loading Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 6 | 16 Participants |
| High Loading Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 9 | 4 Participants |
| High Loading Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 12 | 6 Participants |
| High Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 12 | 3 Participants |
| High Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 6 | 11 Participants |
| High Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Baseline | 24 Participants |
| High Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 3 | 17 Participants |
| High Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Week 6 | 22 Participants |
| High Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 9 | 4 Participants |
| Low Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Week 6 | 17 Participants |
| Low Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 3 | 20 Participants |
| Low Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 6 | 13 Participants |
| Low Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 12 | 4 Participants |
| Low Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Month 9 | 6 Participants |
| Low Daily Dose | Count of Participants Who Completed Radiographic Imaging Measures | Baseline | 24 Participants |
| Control Group | Count of Participants Who Completed Radiographic Imaging Measures | Month 9 | 5 Participants |
| Control Group | Count of Participants Who Completed Radiographic Imaging Measures | Month 12 | 5 Participants |
| Control Group | Count of Participants Who Completed Radiographic Imaging Measures | Week 6 | 19 Participants |
| Control Group | Count of Participants Who Completed Radiographic Imaging Measures | Month 6 | 13 Participants |
| Control Group | Count of Participants Who Completed Radiographic Imaging Measures | Baseline | 27 Participants |
| Control Group | Count of Participants Who Completed Radiographic Imaging Measures | Month 3 | 16 Participants |
Secondary
Number of Participants With Adherence With Vitamin D Supplementation
Will measure adherence with vitamin D supplementation based on participants self report at the 6 week and 3 month visits.
Time frame: Up to 3 months post-injury
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Loading Dose | Number of Participants With Adherence With Vitamin D Supplementation | 6 Weeks | 19 Participants |
| High Loading Dose | Number of Participants With Adherence With Vitamin D Supplementation | 3 Months | 21 Participants |
| High Daily Dose | Number of Participants With Adherence With Vitamin D Supplementation | 3 Months | 19 Participants |
| High Daily Dose | Number of Participants With Adherence With Vitamin D Supplementation | 6 Weeks | 20 Participants |
| Low Daily Dose | Number of Participants With Adherence With Vitamin D Supplementation | 6 Weeks | 18 Participants |
| Low Daily Dose | Number of Participants With Adherence With Vitamin D Supplementation | 3 Months | 19 Participants |
| Control Group | Number of Participants With Adherence With Vitamin D Supplementation | 6 Weeks | 22 Participants |
| Control Group | Number of Participants With Adherence With Vitamin D Supplementation | 3 Months | 20 Participants |
Secondary
Number of Participants With Adverse Events (AE)
A count of the participants who experienced adverse events will measure participant safety
Time frame: Up to 12 months post-injury
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Loading Dose | Number of Participants With Adverse Events (AE) | 9 Participants |
| High Daily Dose | Number of Participants With Adverse Events (AE) | 10 Participants |
| Low Daily Dose | Number of Participants With Adverse Events (AE) | 11 Participants |
| Control Group | Number of Participants With Adverse Events (AE) | 14 Participants |
Secondary
Serum Level of 25(OH)D
Correlations will be assessed between participants' 25(OH)D levels at enrolment, changes in 25(OH)D levels from enrolment to 3 months, and 25(OH)D levels at 3 months and fracture healing
Time frame: Up to 3 months post-injury
Population: Serum 25(OH)D Concentration by Treatment Group
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Loading Dose | Serum Level of 25(OH)D | Baseline | 18.8 ng/mL | Standard Deviation 7.8 |
| High Loading Dose | Serum Level of 25(OH)D | Month 3 | 39.9 ng/mL | Standard Deviation 17.9 |
| High Loading Dose | Serum Level of 25(OH)D | Week 6 | 39.3 ng/mL | Standard Deviation 17.8 |
| High Daily Dose | Serum Level of 25(OH)D | Baseline | 20.7 ng/mL | Standard Deviation 9.6 |
| High Daily Dose | Serum Level of 25(OH)D | Month 3 | 28.2 ng/mL | Standard Deviation 20.7 |
| High Daily Dose | Serum Level of 25(OH)D | Week 6 | 38.4 ng/mL | Standard Deviation 18.6 |
| Low Daily Dose | Serum Level of 25(OH)D | Week 6 | 35.5 ng/mL | Standard Deviation 22.5 |
| Low Daily Dose | Serum Level of 25(OH)D | Baseline | 19.7 ng/mL | Standard Deviation 7.9 |
| Low Daily Dose | Serum Level of 25(OH)D | Month 3 | 38.1 ng/mL | Standard Deviation 19.8 |
| Control Group | Serum Level of 25(OH)D | Baseline | 17.3 ng/mL | Standard Deviation 7.5 |
| Control Group | Serum Level of 25(OH)D | Month 3 | 23.1 ng/mL | Standard Deviation 19 |
| Control Group | Serum Level of 25(OH)D | Week 6 | 26.1 ng/mL | Standard Deviation 15.4 |
Secondary
Serum Levels of Calcium
Will measure participant safety
Time frame: Up to 3 months post-injury
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Loading Dose | Serum Levels of Calcium | Month 3 | 9.5 mg/dL | Standard Deviation 0.3 |
| High Loading Dose | Serum Levels of Calcium | baseline | 9.1 mg/dL | Standard Deviation 0.6 |
| High Loading Dose | Serum Levels of Calcium | Week 6 | 9.6 mg/dL | Standard Deviation 0.3 |
| High Daily Dose | Serum Levels of Calcium | Week 6 | 9.6 mg/dL | Standard Deviation 0.3 |
| High Daily Dose | Serum Levels of Calcium | baseline | 8.8 mg/dL | Standard Deviation 0.7 |
| High Daily Dose | Serum Levels of Calcium | Month 3 | 9.6 mg/dL | Standard Deviation 0.5 |
| Low Daily Dose | Serum Levels of Calcium | Week 6 | 9.6 mg/dL | Standard Deviation 0.4 |
| Low Daily Dose | Serum Levels of Calcium | baseline | 8.3 mg/dL | Standard Deviation 1.8 |
| Low Daily Dose | Serum Levels of Calcium | Month 3 | 9.7 mg/dL | Standard Deviation 0.4 |
| Control Group | Serum Levels of Calcium | baseline | 9.0 mg/dL | Standard Deviation 0.6 |
| Control Group | Serum Levels of Calcium | Month 3 | 9.6 mg/dL | Standard Deviation 0.3 |
| Control Group | Serum Levels of Calcium | Week 6 | 9.6 mg/dL | Standard Deviation 0.5 |
Secondary
Serum Levels of Parathyroid Hormone
Helps the body to maintain stable levels of calcium in the blood
Time frame: Up to 3 months post-injury
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Loading Dose | Serum Levels of Parathyroid Hormone | Baseline | 69.6 pg/mL | Standard Deviation 39 |
| High Loading Dose | Serum Levels of Parathyroid Hormone | Month 3 | 42.4 pg/mL | Standard Deviation 39.6 |
| High Loading Dose | Serum Levels of Parathyroid Hormone | Week 6 | 41.9 pg/mL | Standard Deviation 47.7 |
| High Daily Dose | Serum Levels of Parathyroid Hormone | Baseline | 64.7 pg/mL | Standard Deviation 37.2 |
| High Daily Dose | Serum Levels of Parathyroid Hormone | Month 3 | 71.0 pg/mL | Standard Deviation 68 |
| High Daily Dose | Serum Levels of Parathyroid Hormone | Week 6 | 28.8 pg/mL | Standard Deviation 32.2 |
| Low Daily Dose | Serum Levels of Parathyroid Hormone | Week 6 | 68.0 pg/mL | Standard Deviation 63.2 |
| Low Daily Dose | Serum Levels of Parathyroid Hormone | Baseline | 67.8 pg/mL | Standard Deviation 35.1 |
| Low Daily Dose | Serum Levels of Parathyroid Hormone | Month 3 | 63.1 pg/mL | Standard Deviation 48.1 |
| Control Group | Serum Levels of Parathyroid Hormone | Baseline | 60.3 pg/mL | Standard Deviation 31.1 |
| Control Group | Serum Levels of Parathyroid Hormone | Month 3 | 74.6 pg/mL | Standard Deviation 60.6 |
| Control Group | Serum Levels of Parathyroid Hormone | Week 6 | 43.6 pg/mL | Standard Deviation 47.7 |