NCT02786498

Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing

A Blinded Exploratory Randomized Controlled Trial (RCT) to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 102 (actual)
• Sponsor: University of Maryland, Baltimore · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Fracture

Interventions

Type	Name	Description
DRUG	Vitamin D3
OTHER	Placebo

Timeline

• Start date: 2016-11-21
• Primary completion: 2019-08-01
• Completion: 2021-12-01
• First posted: 2016-06-01
• Last updated: 2022-03-31
• Results posted: 2021-04-01

Locations

2 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study