Risk Factors for Development of Non-union of Displaced Midshaft Clavicle Fractures (RisC)

February 3, 2025 updated by: Ida Tryggedsson, Bispebjerg Hospital

Risk Factors for Development of Non-union of Displaced Midshaft Clavicle Fractures: a Prospective Double-center Cohort Study

Clavicle fractures are common and usually heal well without surgery. Most patients recover full shoulder function within a few weeks with conservative treatment, which is the standard in Denmark. However, in cases where the broken ends of the bone do not touch (displaced fractures), there is a higher risk of complications like non-healing (non-union), affecting 11-18% of such cases. Non-union can lead to long-term pain, reduced shoulder function, and a longer recovery time, often requiring multiple follow-up visits.

While surgery might prevent these complications for some patients, operating on all displaced fractures would lead to overtreatment. The current challenge is identifying which patients are at risk for non-union and would benefit most from surgery. This study aims to investigate the risk factors for non-union in patients with displaced clavicle fractures by examining both patient characteristics and fracture-related factors.

The goal is to use multiple data points to develop a score that can support clinicians and patients in shared decision-making regarding the optimal and individualized treatment for clavicle fractures.

This research is important not only for clavicle fractures but also for understanding and treating non-union in other bones like the ulna and tibia, which face similar challenges.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Clavicle fracture The clavicle, the collarbone, connects the arm to the axial skeleton. It is essential to shoulder function as it provides attachment for the primary muscles stabilizing the shoulder joint, and allows an extensive range of motion by the upper limb.

The clavicle fracture is a common skeletal injury that accounts for approximately 5% of all adult fractures and 35-40% of injuries to the shoulder girdle. According to extensive epidemiological studies, the majority of clavicle fractures occur in the middle third, with 50-70% of those being displaced. It means that for every 100 clavicle fractures, approximately half of them are displaced midshaft fractures.

A clavicle fracture is frequently caused by a direct impact to the shoulder, often resulting from same-level falls, bicycle accidents, or sports-related incidents, which makes it a common fracture in Denmark. There is a classic bimodal distribution of the fracture with increased incidence in younger males, usually due to high-energy trauma, and a second peak in the elderly population often associated with low-energy falls. According to the Danish Health Data Authority, the incidence of clavicle fractures is relatively high, approximately 65/100,000 from 1996-2018, and numbers have been increasing throughout the years.

Most clavicle fractures heal uneventfully and are traditionally treated non-operatively with immobilization in an arm sling for a few weeks, typically attaining full recovery and range of motion within six weeks.

Clavicle non-union Fracture non-union is a rare but severe complication that affects 5-10% of all fractures worldwide, depending on fracture location and country. The risk of non-union is higher when the fracture is displaced and bone ends shift out of their normal alignment, especially in the clavicle, which has one of the highest rates of non-union. Non-union can cause long-term pain, physical disability, reduced quality of life, and an extended recovery period before returning to regular work productivity. Often a non-union requires later complex operative treatment.

Although the incidence of non-union in the clavicle is approximately 10%, performing surgery on all displaced clavicle fractures would lead to overtreatment of fractures that would have healed uneventfully without surgery. Therefore, it is essential to identify patients predisposed to non-union and the risk factors involved to personalize the initial treatment. However, it is a major clinical challenge to identify these patients.

Recent studies on clavicle fractures have focused on comparing the outcomes of non-operative and operative treatment. Despite various randomized controlled trials, a Cochrane review from 2019 concluded that there is limited evidence for choosing one treatment over the other and that the choice of care must be determined on an individual patient basis.

Risk factors Various studies have examined the predictors associated with non-union, and many have found it to be a multifactorial issue. The degree of displacement, or the distance between bone ends, is usually the most significant factor in predicting non-union. Other risk factors include female gender, older age, smoking, persistent pain, fracture comminution, fracture shortening, and absence of developing bridging callus at the fracture site. Typically, the more risk factors present, the greater the risk of non-union. When evaluating patient-related factors, studies usually look at factors related to the host's physiological state, including gender, age, comorbidities, smoking and alcohol status, weight, BMI, and occupation. To cover patient-related factors, it is also necessary to assess the patient's molecular environment, meaning biomarkers for bone health to be found in the blood.

Rationale Research exploring risk factors that predispose patients to the development of symptomatic non-union of clavicle fractures is lacking. Before treatment can be individualized, clinical studies assessing possible risk factors are needed to fill this knowledge gap.

Hypothesis Patients suffering a displaced midshaft clavicle fracture are not at equal risk of development of non-union following conservative treatment.

10% is expected to develop a non-union within 6 months following the injury and the investigators expect to uncover specific clinical, radiological and molecular risk factors for non-union.

Purpose

Overall aim:

The purpose of this study is to identify risk factors for the development of non-union following a displaced midshaft clavicle fracture. The investigators aim to combine clinical, radiological, and molecular risk factors for the establishment of a predictive risk score that may help to assess individual susceptibility to non-union. A risk score combining all aspects will be a practical tool to aid clinicians in identifying and managing patients with increased risk of non-union at the time of initial presentation. This enables individualized treatment and a chance to improve overall outcome for the patient.

Study Type

Observational

Enrollment (Estimated)

250

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 Contact Backup

Study Locations

  • Denmark
      • Copenhagen NV, Denmark, 2400
        • Recruiting
        • Bispebjerg Hospital
        • Contact:
        • Contact:
          • Arvind von Keudell, MD, MPH, PhD
        • Contact:
          • Ida Tryggedsson, MD
        • Contact:
          • Arvind von Keudell, MD, MPH, PhD, Ass.professor
        • Contact:
          • Ilija Ban, MD, PhD
        • Contact:
          • Soeren Overgaard, Md, PhD, Professor
        • Contact:
          • Michael Kuhlman, MD
      • Hvidovre, Denmark
        • Recruiting
        • Hvidovre Hospital
        • Contact:
        • Contact:
        • Contact:
          • Ida Tryggedsson, MD
        • Contact:
          • Tazio Maleitzke, Dr. Med, MD, Ass. professor

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients at age 18 years or above with a displaced midshaft clavicle fracture in the are of Bispebjerg Hospital and Hvidovre Hospital.

Description

Inclusion Criteria:

  • 18 years of age upon study enrollment
  • Admitted to the emergency room (ER) at BBH or HVH with a displaced midshaft clavicle fracture
  • Danish social security number
  • Understand Danish
  • Able to fill out questionnaire by hand or online.
  • Provides informed consent prior to initiation of any study-related activities/procedures

Exclusion Criteria:

  • Subject incapable of understanding the patient information or unable to provide informed consent
  • Open fracture or fracture with risk of skin penetration
  • Pathological fracture
  • Clavicle fracture due to polytrauma
  • Floating shoulder injury
  • Vascular injury at fracture site
  • 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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients at age 18 or above with a displaced midshaft clavicle fracture.
Other: Non-union
Observational study looking prospectively at many different factors that may affect non-union of midshaft clavicle fractures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic Non-Union assessed by 2-plane radiograph at 26 weeks post-injury
Time Frame: 26 weeks

Measure: Radiographic assessment of non-union using standard 2-plane radiographs at 26 weeks post-injury.

Non-Union Assessment: Non-union will be defined as the absence of bridging callus on radiographs at 6 months post-injury, measured on standard 2-plane radiographs of the clavicle. The assessment will include measurement of displacement and shortening (measured in millimeters).
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual Analog Scale (VAS) score
Time Frame: Week 1 to week 6

Measure: The Visual Analog Scale (VAS) score is used to measure a person's subjective experience of pain on a scale from 0 to 10, with 0 being no pain and 10 being the worst possible pain. Participants will record a VAS-score daily from week 1 to week 6.

Purpose: To investigate if patients who suffer prolonged pain and thus will not show a significant improvement in Visual Analog Scale (VAS) score within 6 weeks from injury are predisposed to the development of non-union.
Week 1 to week 6
Shoulder function measured by the quick Disabilities of the Arm, Shoulder and Hand (qDASH) score
Time Frame: 1 week, 6 weeks, 12 weeks, 26 weeks, 52 weeks

Measure: The quick Disabilities of Arm Shoulder Hand (qDASH) measures physical function and symptoms in people with musculoskeletal disorders of the upper limb. The qDASH consists of 11 items that patients rate on a scale of 1 (no difficulty or no symptoms) to 5 (extreme difficulty or severe symptoms). The responses are averaged and then transformed into a score on a scale from 0 to 100.

Purpose: To investigate if patients who do not show a significant improvement in range of motion of the shoulder and no significant increase in qDASH score are predisposed to development of non-union.
1 week, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Quality of Life measured by the EuroQol (EQ-5D-5L) questionnaire
Time Frame: 1 week, 6 weeks, 12 weeks, 26 weeks, 52 weeks.

Measure: The EuroQol (EQ-5D-5L) questionnaire is used to assess patient-reported outcomes related to health-related quality of life. It evaluates five dimensions, each rated on a 5-point scale, where 1 represents no issues and 5 represents severe issues. The EQ-5D-5L can describe up to 3,125 different health states. A score of 11111 signifies no problems in any dimension, while a score of 55555 reflects extreme problems across all dimensions.

Purpose: To investigate whether patients who do not show significant improvement in their EQ-5D-5L score are at increased risk of developing non-union following non-operative treatment.
1 week, 6 weeks, 12 weeks, 26 weeks, 52 weeks.
Radiographic assessment of fracture characteristics
Time Frame: 1 week, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Measure: Radiographic assessment of non-union using standard 2-plane radiographs. Assessment will include description of callus formation (binary: yes/no) and measurement of displacement and shortening (millimeter).
1 week, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Plasma concentration of health-related biomarkers
Time Frame: 1 week

Measure: Blood sample collected at 1 week post injury. The sample will be analyzed for concentration of 25-hydroxyvitamin D, Calcium, Phosphorus, Bone-specific Alkaline Phosphatase, Alkaline Phosphatase, Magnesium, HbA1c, Intact parathyroid hormone, Insulin-like growth factor 1, Thyroid function tests, Free testosterone, Estradiol, Complete blood count (CBC), P1NP (procollagen), osteocalcin, calcitonin, CGRP, RAKL, sclerostin.

Purpose: To assess if any abnormal levels of biomarkers at 1 week affect development of non-union at 26 weeks.
1 week
Patient-related factors extracted from medical record
Time Frame: Week 1
Measure: Data extracted from patient medical records including demographic information, gender, height, weight, smoking status, weekly alcohol consumption, medicine use, comorbidities, and employment status Purpose: To investigate if any patient-related factors present at week 1 predispose for development of non-union at 26 weeks.
Week 1

Collaborators and Investigators

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

Sponsor

Bispebjerg 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)

October 21, 2024

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

October 18, 2024

First Submitted That Met QC Criteria

October 21, 2024

First Posted (Actual)

October 22, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 3, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-24022926

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not allowed due to study approval from national ethics comite.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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