HO Prophylaxis Therapy for Distal Humerus Fractures

January 25, 2022 updated by: Rodolfo Zamora, MD, University of Louisville

Prophylaxis Low-Dose Radiation Therapy for Heterotopic Ossification in Distal Humerus Fractures

To determine the effectiveness of 500 cGy dose of radiation therapy vs. an untreated group in the prophylactic treatment of heterotopic ossification in distal humerus fractures

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Heterotopic ossification is the formation of ectopic lamellar bone in the soft tissues. The process is thought to occur through local and distal recruitment osteoprogenitor cells especially mesenchymal stem cells which lead to HO formation based on local microenvironmental factors including activation of the BMP-mediated pathways.1 There are several risk factors associated with HO development such as central nervous system injury, thermal burn, hip arthroplasty, acetabular fractures, and elbow fractures; HO is also seen with certain arteriopathies and genetic conditions e.g. ankylosing spondylitis, seronegative arteriopathies, diffuse idiopathic skeletal hyperostosis (DISH), and fibrodysplasia ossificans progressive. In elbow fractures, the prevalence of HO is around 40%, and of those that develop HO, 20% experience a clinically relevant decrease in elbow range of motion with a flexion-extension arc of <100°. In a study by Foruria, et al. of 89 patients with a distal humerus fracture without associated proximal radius or ulna fracture that underwent surgical treatment with ORIF, 42% developed HO and the HO in these patients was associated with significantly less extension and a limited flexion-extension arc but was not associated with a change in supination or pronation. Abrams, et al. looked at the development of HO after elbow fracture fixation in 89 pts including 20 distal humerus fractures and found that distal humeral fractures were more likely to have higher grade of HO, have more compromised functional outcomes, and require return to the OR more often for capsular release with HO resection at a rate of 25%. Prophylactic treatment for HO is most commonly achieved through the use of NSAIDs such as indomethacin and radiation therapy. Both modalities have the risk of nonunion of fracture and radiation therapy has additional risks such as delayed wound healing, soft tissue contracture, and the theoretical risk of malignancy although no cases of malignancy after prophylactic radiation have been reported to date. Radiation therapy in the prevention of HO has been well studied in the hip with low-dose radiation being established as an effective dose and 700cGy as the most commonly used dose.5 Radiation therapy in the prevention of HO at the elbow is not as well studied and existing studies have commonly used a dose of 700cGy. One study looked at the use of radiation therapy in combination of patients being treated acutely for elbow trauma and patients being treated for HO after previous elbow trauma, and the study found that 3 of the 36 patients developed new HO and found an occurrence of 2 nonunion with the majority treated with 700cGy but 2 pts received 600cGy.6 Heyd, et al. present a case series of 9 patients that underwent surgical excision of clinically significant HO at the elbow and received radiation therapy of 2 doses of 500cGy, 1 dose of 600 cGy , or 1 dose of 700 cGy ; at a mean follow up of 7.7 no patients had recurrence of HO and 8 of 9 showed clinical improvement.7 A study of 11 patients that underwent ORIF for fracture-dislocation of the elbow and single-dose radiation therapy of 700 cGy within 72 hours postoperatively, and 3 patients (27%) developed radiographic evidence of HO while 10 patients (91%) had no functional limitations and 100% of patients completely healed there fracture without complications at average follow up of 12 months (9-24 months). 3 of the 11 patients had distal humerus fractures and none of them had radiographic evidence of HO or functional limitation.8 A recent multicenter randomized control trial of patients with intraarticular distal humerus fractures or fracture-dislocation of the elbow with proximal ulna and/or radius fracture randomized patients to either receive a single dose of 700cGy within 72 hours postop or receive nothing for HO prophylaxis. Although, HO occurrence in the 21 patients in the treatment group vs the 24 in the control group (33% vs 54%), the rate of nonunion was higher in the treatment group (38% vs 4%) resulting in termination of the study. Several studies have demonstrated the efficacy and safety of radiation therapy in the prophylactic treatment of HO in the elbow, but the study by Hamid questions the use of a 700 cGy dose because of the rate of nonunion observed. Thus, the investigators hypothesize that a dose of 500 cGy will be adequate in the elbow HO prevention as there is smaller treatment area compared to the hip where 700 cGy is an effective dose and that this dose will not result in an increased rate of nonunion.

Early osteoprogenitor cells involved in bone repair are thought to be more radiosensitive than the more mature cells seen later in the development of bone formation after fracture. Thus, radiation specifically works to inhibit the osteogenic pathway. Based on a recent Cochrane review, the incidence of HO development with any dose of RT was 24%. The was no correlation with site (hip, elbow, knee) or radiation dose, which ranged from 500cGy - 2000cGy. The most commonly used regimen was 700cGy (60%) while dose less than 700cGy represented 12%. The problem with 700cGy is the reported rate of non-union is as high as 40%, especially when the elbow is treated. Additionally, increasing radiation dose alters the expression of transforming growth factor-beta 1, vascular endothelial growth factor, and alkaline phosphatase which can prevent bone union. Based on this data, 500cGy should still be adequate to inhibit the osteogenic pathway by causing lethal damage to osteoprogenitor cells while at the same potentially allowing for a better bone union.

Study Type

Interventional

Enrollment (Actual)

3

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 Locations

  • United States
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Hospital
      • Louisville, Kentucky, United States, 40228
        • University of Louisville Hospital

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient has a distal humerus fracture.
  2. Patient's age is greater than or equal to 18

Exclusion Criteria:

  1. Patient has a concomitant proximal ulna and/or proximal radius fracture
  2. Patient requires external fixation of the elbow
  3. Patient has quadriplegia or paraplegia
  4. Patient requires intubation upon admission or for >4 hours during admission for nonsurgical purposes
  5. Patient has concomitant soft tissue damage in the affected elbow that cannot be appropriately closed within 72 hours of surgery
  6. Patient has a burn affecting greater than or equal to 20% of the total body surface area or on the affected elbow
  7. Patient has pre-existing heterotopic ossification in the affected elbow.
  8. Patient is pregnant.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
This group will receive the standard of care treatment for their distal humerus fracture only.
Experimental: Intervention
This group will receive the prophylactic radiation therapy in addition to the standard of care treatment of their distal humerus fracture.
Radiation: Radiation
A dose of 500cGy will be delivered in 1 fraction to the isocenter. Radiation will be administered no later than 72 hours postoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Presence of HO on Humerus
Time Frame: 1 year. The control patient completed 366 days of follow up. The two intervention patients lost follow up after 155 days and 62 days.
Presence of heterotopic ossification on plain radiographs taken in the anteroposterior and lateral planes within 1 year after surgery as quantified using the classification systems described by Brooker, et al. and Hastings and Graham
1 year. The control patient completed 366 days of follow up. The two intervention patients lost follow up after 155 days and 62 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-union at the Fracture Site.
Time Frame: 1 year post surgical reduction. The control patient completed 366 days of follow up. The two intervention patients lost follow up after 155 days and 62 days respectively.
Rate of non-union of both groups requiring revision surgery.
1 year post surgical reduction. The control patient completed 366 days of follow up. The two intervention patients lost follow up after 155 days and 62 days respectively.

Collaborators and Investigators

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

Sponsor

University of Louisville

Investigators

  • Principal Investigator: Rodolfo Zamora, MD, University of Louisville

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)

October 9, 2019

Primary Completion (Actual)

November 17, 2020

Study Completion (Actual)

November 17, 2020

Study Registration Dates

First Submitted

September 20, 2018

First Submitted That Met QC Criteria

October 26, 2018

First Posted (Actual)

October 30, 2018

Study Record Updates

Last Update Posted (Actual)

February 15, 2022

Last Update Submitted That Met QC Criteria

January 25, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB Number:18.0184

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No plan at this time to Share IPD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

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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