Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing
Condition: Fracture
MeSH terms: Fractures, Bone
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Vitamin D3; Placebo
Intervention type(s): Drug; Other
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Tibial Shaft; Tibia; Femoral Shaft; Femur; Vitamin D; Fracture Healing