The Effect of Hypovitaminosis D and Vitamin D Supplementation on Fracture Nonunion Rates

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of Hypovitaminosis D and Vitamin D Supplementation on Fracture Nonunion Rates

Conditions
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Hypovitaminosis D

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>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. | Dietary Supplement: Vitamin D<br>* Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.<br>|
| Placebo Comparator: Placebo<br>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. | Dietary Supplement: Placebo<br>* Patients that are Vitamin D deficient maybe randomized to the placebo group D.<br>|
| No Intervention: Normovitaminosis<br>Patients with normovitaminosis( levels greater than or equal to 30ng/ml) will receive no intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 9 months post-surgery | 
| 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. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fixation Failure | Early failure of fixation was defined as the need to revise the fixation within three months. | three months | 
| Deep Infection | A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia. | 15 months | 
| 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. | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, nonunion, long bone fracture, hypovitaminosis D