Hypovitaminosis D
Conditions
Keywords
Vitamin D, nonunion, long bone fracture, hypovitaminosis D
Brief summary
The purpose of the study is to determine whether vitamin D supplementation in patients with hypovitaminosis D can decrease nonunion (failure to heal) incidence in patients with fractures of the humerus, femur, or tibia. The central hypothesis of the study is that vitamin D supplementation in patients with fractures and hypovitaminosis D will decrease the risk of nonunion compared to placebo treatment.
Detailed description
Vitamin D plays an important role in maintaining calcium and phosphate balance in the body and is important for maintenance of bone formation, remodeling, and healing. An extensive literature search indicates that although there is evidence that vitamin D deficiency is associated with fracture risk, there is no evidence of the role of vitamin D deficiency in subsequent failure to heal. The aims of study were to: 1) quantify the rate of hypovitaminosis D in an orthopedic trauma population in the Southeastern United States; 2) determine the rate of nonunion in vitamin D deficient patients, and 3) assess the feasibility of acute high-dose vitamin-D supplementation in hypovitaminosis D patients.
Interventions
DIETARY_SUPPLEMENTVitamin D
Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.
DIETARY_SUPPLEMENTPlacebo
Patients that are Vitamin D deficient maybe randomized to the placebo group D.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* presence of a long bone fracture (humerus, femur, or tibia) * age greater than or equal to 18 years * ability to follow-up at our clinic for 12 months
Exclusion criteria
* pathologic fractures (i.e. occuring in the presence of abnormal bone such as a tumor, cyst, or Paget's disease) * open fractures (i.e. associated skin disruption) of Gustilo-Anderson type IIIB or C (i.e. significant soft-tissue and bone devitalization) * presence of multiple fractures * delay in presentation for initial treatment of more than 2 weeks from the time of injury * preexisting disorders known to adversely affect bone healing (e.g. diabetes mellitus with HbA1C greater than or equal to 7, peripheral vascular disease, certain connective tissue disorders, and congenital or acquired disorders of bone metabolism) * preexisting disorders affecting Vitamin D metabolism and/or calcium phosphate homeostasis (e.g. renal failure, hepatic failure, congenital defects in vitamin D metabolism, parathyroid disorders, conditions causing abnormal calcium and/or phosphate absorption) * pregnant patients * patients who are unable to provide consent for the study * patients who are unable to swallow due to acuity of illness or physiologic reason * prisoners who are patients because of their vulnerable population and inability to follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fracture Union | up to 9 months post-surgery | Fracture Union is define as either clinical or radiological union. Clinical union defined as the absence of pain at the fracture site with the ability to bear full weight on the extremity without pain for activities of daily living (ambulation, lifting, carrying). Radiological union was determined by two blinded, independent review-ers and defined as the presence of bridging callus across at least three of four cortices or two of four cortices with a stable implant. When discrepancies between clinical and radiological union arose, the clinical assessment of union was preferred. Discrepancies in radiological outcomes were re-examined and a consensus view was obtained between reviewers if needed, to determine the outcome.If a patient did not meet the criteria for union and had at least nine months of follow•up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion. |
| Fracture Non-union | 9 months | If a patient did not meet the criteria for union and had at least nine months of follow-up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fixation Failure | three months | Early failure of fixation was defined as the need to revise the fixation within three months. |
| Deep Infection | 15 months | A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia. |
| Lost to Follow-up | 15 months | Lost to follow-up if they did not meet the criteria for an outcome by 15 months after injury or surgery; were without another scheduled follow-up appointment, could not be contacted or refused to return for evaluation or send alternate records when contacted. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D. | 50 |
| Placebo Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D. | 50 |
| Normovitaminosis Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study. | 13 |
| Total | 113 |
Baseline characteristics
| Characteristic | Total | Vitamin D | Placebo | Normovitaminosis |
|---|---|---|---|---|
| Age, Customized | 37.4 years STANDARD_DEVIATION 12.6 | 38.9 years STANDARD_DEVIATION 13.1 | 35.5 years STANDARD_DEVIATION 12.1 | 39.9 years STANDARD_DEVIATION 11.7 |
| BMI | 28.3 kg/m2 STANDARD_DEVIATION 6.5 | 29.4 kg/m2 STANDARD_DEVIATION 6.3 | 27.8 kg/m2 STANDARD_DEVIATION 6.5 | 25.5 kg/m2 STANDARD_DEVIATION 4.87 |
| Diabetes mellitus | 4 Participants | 0 Participants | 4 Participants | 0 Participants |
| Injury Type Femur | 55 Participants | 25 Participants | 25 Participants | 5 Participants |
| Injury Type Humerus | 18 Participants | 8 Participants | 7 Participants | 3 Participants |
| Injury Type Tibia | 40 Participants | 17 Participants | 18 Participants | 5 Participants |
| Operatively treated | 94 Participants | 41 Participants | 42 Participants | 11 Participants |
| Prior use of Vitamins | 71 Participants | 29 Participants | 36 Participants | 6 Participants |
| Sex: Female, Male Female | 33 Participants | 16 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Male | 80 Participants | 34 Participants | 38 Participants | 8 Participants |
| Tobacco use ( current) | 55 Participants | 24 Participants | 23 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 13 |
| other Total, other adverse events | 0 / 50 | 0 / 50 | 0 / 13 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 | 0 / 13 |
Outcome results
Primary
Fracture Non-union
If a patient did not meet the criteria for union and had at least nine months of follow-up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypovitaminosis- Vitamin D Group | Fracture Non-union | 2 Participants |
| Hypovitaminosis- Placebo Group | Fracture Non-union | 2 Participants |
| Normovitaminosis | Fracture Non-union | 3 Participants |
Primary
Fracture Union
Fracture Union is define as either clinical or radiological union. Clinical union defined as the absence of pain at the fracture site with the ability to bear full weight on the extremity without pain for activities of daily living (ambulation, lifting, carrying). Radiological union was determined by two blinded, independent review-ers and defined as the presence of bridging callus across at least three of four cortices or two of four cortices with a stable implant. When discrepancies between clinical and radiological union arose, the clinical assessment of union was preferred. Discrepancies in radiological outcomes were re-examined and a consensus view was obtained between reviewers if needed, to determine the outcome.If a patient did not meet the criteria for union and had at least nine months of follow•up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.
Time frame: up to 9 months post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypovitaminosis- Vitamin D Group | Fracture Union | 40 Participants |
| Hypovitaminosis- Placebo Group | Fracture Union | 39 Participants |
| Normovitaminosis | Fracture Union | 10 Participants |
Secondary
Deep Infection
A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia.
Time frame: 15 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypovitaminosis- Vitamin D Group | Deep Infection | 0 Participants |
| Hypovitaminosis- Placebo Group | Deep Infection | 1 Participants |
| Normovitaminosis | Deep Infection | 0 Participants |
Secondary
Fixation Failure
Early failure of fixation was defined as the need to revise the fixation within three months.
Time frame: three months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypovitaminosis- Vitamin D Group | Fixation Failure | 1 Participants |
| Hypovitaminosis- Placebo Group | Fixation Failure | 1 Participants |
| Normovitaminosis | Fixation Failure | 0 Participants |
Secondary
Lost to Follow-up
Lost to follow-up if they did not meet the criteria for an outcome by 15 months after injury or surgery; were without another scheduled follow-up appointment, could not be contacted or refused to return for evaluation or send alternate records when contacted.
Time frame: 15 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypovitaminosis- Vitamin D Group | Lost to Follow-up | 7 Participants |
| Hypovitaminosis- Placebo Group | Lost to Follow-up | 7 Participants |
| Normovitaminosis | Lost to Follow-up | 0 Participants |