Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications

August 14, 2023 updated by: Antonia Faustina Chen, Brigham and Women's Hospital
Vitamin D status has been shown to have an effect on post-operative outcomes in total joint arthroplasty. The goal of this study is to determine if pre-operative supplementation and correction of Vitamin D deficiency can reduce postoperative complications.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Total joint arthroplasty (TJA) is one of the most common surgical procedures performed in the United States (US), with approximately 2.5 million individuals with total hip arthroplasties (THAs) and 4.7 million individuals with total knee arthroplasties (TKAs) in 2010. Patients who undergo TJA commonly have Vitamin D deficiency, with rates reported to be 24-61% in primary TJA patients. Vitamin D deficiency affects women and minorities at high rates, in addition to non-Hispanic whites. Previous studies demonstrated that Vitamin D deficiency poorly impacts outcomes after various surgical procedures. Specifically in TJA patients, recent studies show a higher rate of Vitamin D deficiency in periprosthetic joint infection (PJI) patients, and a higher rate of postoperative complications and infection in revision TJA patients with low Vitamin D. In a PJI mouse model, Vitamin D-deficient mice were shown to have an increased bacterial burden when compared to Vitamin D-deficient mice that received "rescue" cholecalciferol (Vitamin D3) supplementation. Bacterial burden was similarly decreased between normal mice and the Vitamin D-deficient "rescue" mice receiving supplementation. A single dose of Vitamin D3 supplementation in Vitamin D-deficient mice using the same mouse model reversed the effect of PJI by decreasing bacterial burden and neutrophil infiltration.

The serum concentration of 25-hydroxycholecalciferol or 25-hydroxyvitamin D (25(OH)D) is the most accurate measure of stores of Vitamin D in the body. There are currently different recommendations regarding the optimal serum 25(OH)D level for bone health, the optimal daily intake of Vitamin D, and the treatments for Vitamin D deficiency or insufficiency. These controversial topics do not provide clear clinical guidance on how to optimize Vitamin D levels in surgical patients to reduce complication rates. The US Institute of Medicine (IOM) committee recommended a 25(OH)D level >20 ng/mL but other organizations recommend ≥30 ng/mL. At present, deficient levels of Vitamin D are generally defined as a 25(OH)D <20 ng/ml, relative insufficiency as 20 to 29 ng/mL, and sufficient levels as ≥ 30 ng/ml. In 2011, the IOM established Recommended Dietary Allowances (RDAs) for Vitamin D of 600-800 IU/d in order to achieve a 25(OH)D level of 20 ng/ml for 97.5% of the general population. The debate concerns recommendations based upon population science, in contrast to care of an individual patient. Thus, there is continuing debate among several groups that recommend higher Vitamin D3 doses and 25(OH)D levels of ≥30 ng/mL for optimal bone health and in high-risk individuals with osteoporosis. The National Osteoporosis Foundation recommends 800 to 1000 IU Vitamin D3 daily for adults aged 50 years and older, as do the International Osteoporosis Foundation and Endocrine Society. The Endocrine Society recommended even higher doses up to 1500 to 2000 IU/d of Vitamin D3 for older adults. For Vitamin D deficiency, the recommended treatment is 50,000 units of Vitamin D3 weekly for 8 weeks with an assay repeat to determine whether Vitamin D-sufficiency ≥30ng/mL was achieved. The proposed study was designed in light of debated recommendations in the literature and should result in rigorous new information about 25(OH)D levels achieved with different doses of Vitamin D3 supplementation and their impact on post-TJA complications.

There are no current studies in literature examining whether preoperative supplementation and correction of Vitamin D deficiency may reduce complications following TJA. The aim of this randomized controlled trial is to evaluate the ability of different doses (low and high dose) of Vitamin D3 supplementation to affect adverse events and functional outcomes following total joint arthroplasty surgery. To conduct this study, investigators propose randomizing subjects with 25(OH)D levels between 10 and 29 ng/mL to receive different doses of Vitamin D to assess the effects of Vitamin D3 supplementation dosage on postoperative TJA complication rates. Consented patients with serum 25(OH)D levels equal or greater than 30 ng/dL will be included in the control group.

Study Type

Interventional

Enrollment (Estimated)

900

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Contact:
        • Principal Investigator:
          • Antonia F Chen, MD, MBA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients ≥18 years of age undergoing elective unilateral primary TJA for osteoarthritis
  • Patients with a pre-operative serum 25(OH)D levels ≥10 ng/mL
  • Patients who consent to the study

Exclusion Criteria:

  • Adult patients ≥18 years of age undergoing elective primary TJA with a pre-operative serum 25(OH)D2,3 level <10 ng/mL
  • Patients undergoing revision surgery
  • Patients lacking mental capacity to comply with study procedures
  • Patients with serum 25(OH)D levels between 10-29 ng/dL refusing to stop their current Vitamin D and multivitamins supplementations
  • Hypercalcemia (total calcium >10.6 mg/dL or ionized serum calcium >5.4mg/dL)
  • History of nephrolithiasis
  • Granulomatous disease
  • Dialysis and advanced kidney disease
  • Previous infection/septic arthritis
  • Inability to swallow Vitamin D3 pills
  • Allergy to Vitamin D3 (It is estimated that 1 in 300 individuals may have an allergy with skin manifestations 17)
  • Hypocalcemia (<8.5 mg/dL)
  • Chronic kidney disease (eGFR <60 mL/minute)
  • Known hyperparathyroidism
  • Known osteoporosis/insufficiency stress fractures (if normal stresses are applied to an abnormal bone)
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low Vitamin D3 Supplementation
Subjects enrolled into Group 1 (low-dose Vitamin D3 supplementation) will receive 800 IU of oral Vitamin D3 (Cholecalciferol) daily for 4 weeks prior to surgery, followed by 800 IU of oral Vitamin D3 daily for 3 months after surgery. Vitamin D3 supplementation will be given for a total of 4 months. Supplementing Vitamin D-deficient patients with a minimum of 800 IU of Vitamin D3 daily is supported by the IOM.
Dietary supplement: Vitamin D3
Vitamin D will be given at doses commonly given to patients with low vitamin D levels
Other Names:
  • cholecalciferol
Active Comparator: High Vitamin D3 Supplementation
Subjects enrolled into Group 2 (high-dose Vitamin D3 supplementation) will receive 50,000 IU of oral Vitamin D3 (Cholecalciferol) twice per week for 1 weeks followed by 50,000 IU once per week for 3 weeks prior to surgery. After surgery they will receive 50,000 IU of oral Vitamin D3 once per week for 4 weeks followed by 800 IU daily for 8 weeks. Vitamin D3 supplementation will be given for a total of 4 months.
Dietary supplement: Vitamin D3
Vitamin D will be given at doses commonly given to patients with low vitamin D levels
Other Names:
  • cholecalciferol
No Intervention: No supplementation
Subjects with serum 25(OH)D level ≥30ng/mL will not receive any Vitamin D supplementation both pre- and postoperatively, as these are considered sufficient. These control patients will be asked to take any supplements containing Vitamin D for the duration of their participation in the trial. All patients in group 3 will have their serum 25(OH)D checked at 3 months after the surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Readmission, reoperation, wound complications, and PJI
Time Frame: Preoperative visit to three months post-op
adverse events
Preoperative visit to three months post-op

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vitamin D status
Time Frame: Day of surgery to to three months post-op
Vitamin D levels will be drawn initially, during supplementation and following
Day of surgery to to three months post-op
Patient-Reported Outcomes Measurement Information System (PROMIS)
Time Frame: Preoperative visit to three months post-op
set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children.41 to 78.3 with higher scores representing worse pain impact.
Preoperative visit to three months post-op
Pain Levels: visual analog scale (VAS)
Time Frame: Preoperative visit to three months post-op
Scores on the VAS pain scale range from 0-10 with 0 being no pain and 10 being the highest pain level imaginable.
Preoperative visit to three months post-op
Hip disability and Osteoarthritis Outcome Score (HOOS)
Time Frame: Preoperative visit to three months post-op
Scores range from 0 to 100 with a score of 0 indicating the worst possible hip symptoms and 100 indicating no hip symptoms
Preoperative visit to three months post-op

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Massachusetts General Hospital
Newton-Wellesley Hospital

Investigators

  • Principal Investigator: Antonia F Chen, MD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2019

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

January 9, 2020

First Submitted That Met QC Criteria

January 11, 2020

First Posted (Actual)

January 18, 2020

Study Record Updates

Last Update Posted (Actual)

August 16, 2023

Last Update Submitted That Met QC Criteria

August 14, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P001701

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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