Three different radiological indicators for diagnosis of adult acetabular dysplasia: study protocol for a diagnostic trial and preliminary results

Di Qin, Xiao-Bo Wu, Hui-Jie Li, Li-Ying He, Tao Wu, Wen-Hui Ma, Shi-Wei Hu, Yong-Tai Han

Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China

INTRODUCTION

Background

Acetabular dysplasia is a developmental malformation of the hip joint where the acetabulum become shallow and cannot fully cover the femoral head and the center of the hip joint moves outward, resulting in an increased risk for joint subluxation or dislocation.1-3

Current diagnosis of acetabular dysplasia mainly depends upon a pelvic anteroposterior X-ray to assess for dislocation of the hip joint, whether the concentricity of the femoral head and acetabulum are consistent, and whether there is secondary osteoarthritis or other hip diseases, such as femoral head ischemic necrosis, hip joint tuberculosis,or rheumatoid arthritis.4-7The commonly used measurement indicators include Wiberg anterior center-edge (CE)angle, acetabular angle (Sharp angle), and acetabular head index (AHI). Some differences exist in the measurement results between male and female patients.8Acetabular dysplasia is often characterized by acetabular bone hyperplasia and necrosis of the femoral head,9-11which have a greater impact on radiographic measurements, especially when measured with angles. It is difficult to determine the radiological landmark for the lateral edge of the acetabular roof in the presence of bone hyperplasia, which produces a great influence on the accuracy of the measurement of the CE angle and the Sharp angle.12-14

Features of the study

We propose a method of measuring the outward and upward displacement of the femoral head relative to the pelvis for the accurate diagnosis of acetabular dysplasia as well as for the better evaluation of the relationship between the femoral head and acetabulum. This is a simple method with relatively small errors.

Objective of the study

Three radiological indicators, offshoring index (OFI),moving up index (MUI) and teardrop baseline offshoring index (TBOI), will be determined in the study, to avoid measurement errors caused by the deviation of the center point of the femoral head, thereby achieving accurate diagnosis of adult acetabular dysplasia.

METHODS/DESIGN

Study design

This is a single-center diagnostic trial. The unaffected hip of each subject will be used as the control.

Study setting

The trial will be completed at the Third Hospital of Hebei Medical University, Hebei Province, China.

Study procedures

A study population will be composed of 100 male and 100 female subjects, who will undergo a pelvic X-ray examination.

Measurement indicators will include OFI, MUI, TBOI,CE angle, Sharp angle, and AHI of the affected and healthy femoral heads. We will determine the sensitivity and specificity of OFI, MUI and TBOI for the diagnosis of adult acetabular dysplasia, and compare the accuracy of diagnosis between these three indicators and CE angle,Sharp angle, and AHI. Further analysis of risk factors for hip function will be implemented.

Trial flow chart is shown in Figure 1.

Eligibility criteria

Figure 1: Trial flow chart.

Inclusion criteria

Patients who meet all of the following aspects will be eligible to be included in the study:

? No previous hip replacement, pelvic fixation or external fixation, or proximal femoral surgery

? No marked pelvic tilt

? No hip dislocation

? No significant collapse of the femoral head and severe hip posttraumatic arthritis

? No tumor lesions in the pelvis or proximal femur

? Unilateral hip pain

? Age > 16 years

? Provision of written informed consent

Exclusion criteria

The following conditions render subjects ineligible for the study:

? Advanced osteoarthritis

? Osteoarthritis secondary to acetabular dysplasia

? Ankylosing spondylitis involving the hip joint

? Rheumatoid arthritis

? Inflammation of the hip joint

? Tumor lesions in the hip joint

Recruitment

Potential subjects will be informed of the study details through an announcement issued through the bulletin board of the Third Hospital of Hebei Medical University.Interested subjects will directly contact the principle investigator via telephone, and among them, eligible subjects will be required to provide written consent prior to the participation in the trial.

Baseline collection

The baseline data to be collected are shown in Table 1.

Sample size

By reference to our experience, we hypothesized that the sensitivity of Ofifor diagnosis of adult acetabular dys-plasia could be up to 95%. Taking two-sided α = 0.05,б = 0.05, and μ0.05= 1.96, the required sample size was calculated to be n = 73 using the formula:

Table 1: Baseline data of all participants

where p refers to sensitivity, б refers to allowable error,α refers to significant level and μ refers to cut-off level.With a predicted loss rate of 20%, we planned to enroll 88 males and 88 females. In accordance with the inclusion and exclusion criteria, 200 adult patients, including 100 males and 100 females, will be actually enrolled in the study.

Randomization and blinding

This is an open-label trial, in which all patients, clinicians and evaluators will be informed of patient allocation and treatment program.

Imaging measurements

Imaging measurement will be performed using a C-arm X-ray machine from GE Healthcare (Milwaukee WI, USA),and imaging indicators will be measured using commercial software (Photoshop CS5?, Adobe Systems, Inc., San Jose CA, USA).

Ofiis determined by the ratio of the distance from the center of the femoral head or the superior edge of the acetabulum to the midline of the body × 100%. The Ofiis used to quantify the outward displacement of the femoral head, with a higher value indicating more severe displacement of the femoral head.

MUI is determined by the ratio of the distance from the center of the femoral head or the “teardrop” to the inferior edge of the acetabulum. The MUI is used to quantify the superior displacement of the femoral head, with a lower value indicating more severe displacement of the femoral head.

TBOI is determined by the ratio of the vertical distance from the center of the femoral head or the superior edge of the acetabulum to the pelvic teardrop. This index is designed to quantify the outward displacement of the femoral head, with a higher value indicating more severe subluxation of the femoral head. The TBOI measurement is simpler than that of the OFI. The TBOI measurement can avoid the error caused by a nonvertical central axis.

The CE angle is an angle between a vertical line and a line from the center of the femoral head to the lateral edge of the acetabular roof. This angle is used to quantify the acetabular anterior and lateral coverage of the femoral head.The CE angle is greatly influenced by the position of the femoral head, especially if the femoral head is dislocated.This can result in a greater error in the measured value,and sometimes it is impossible to measure the CE angle. In addition, it is difficult to measure the CE angle in infants and children whose femoral condyle is not calcified. The normal angle in adults ranges from 20-25°, and an angle <20° indicates acetabular dysplasia. Acetabular dysplasia is present in children aged 3-17 years with a CE angle < 15°.

The Sharp angle is an angle between a line connecting the lateral edge of the acetabular roof and the pelvic teardrop and a second line which extends along the inferior edge of both pelvic teardrops, as shown on the anteroposterior radiographs of the pelvis. This angle provides useful information after the age of 10 years (after the fusion of the triradiate cartilage), and normally measures 39-42°. A Sharp angle > 45° indicates acetabular dysplasia. According to statistics, the range of the Sharp angle is 32.0-44.5°in Chinese men and 34.5-47.5° in Chinese women.

AHI refers to the A/B ratio that indicates the degree of femoral head coverage, where A refers to the distance between the medial edge of the femoral head and the lateral edge of the acetabulum, and B refers to the transverse diameter of the femoral head. In normal adults, it is estimated to be 86% for males and 87% for females, with a lower limit of 76%. It becomes progressively lower with age. The AHI value fully reflects the matching relationship between the femoral head and the acetabulum. An AHI value under the lower limit indicates a subluxation of the hip due to outward displacement of the force-bearing point of the femoral head.

Gold standard for diagnosis of adult acetabular dysplasia

Crowe’s classification15is the most widely used classification system for adult development dysplasia of the hip(DDH). It can be used for diagnosis of adult acetabular dysplasia in combination with the measurement of the CE angle, Sharp angle, and AHI described above (Table 2).

Outcome measures Primary outcome measure

Table 2: Crowe’s classification system for adult development dysplasia of the hip

The sensitivity of Ofifor diagnosing adult acetabular dysplasia will be the primary outcome measure. The sensitivity represents the percentage of actual patients who are correctly diagnosed with a disease. A higher sensitivity indicates a higher rate of correct diagnosis for acetabular dysplasia.

Secondary outcome measures

(1) The specificity, positive and negative predictive values,and positive and negative likelihood ratios of Ofiof the femoral head for diagnosing adult acetabular dysplasia as well as the rate of correct diagnosis.

? The specificity represents the percentage of disease-free patients who are correctly diagnosed with no disease.A higher specificity indicates a higher rate of correct diagnosis for acetabular dysplasia.

? The positive predictive value represents the probability that the patient actually suffer from the disease (true positive rate) in all positive cases.

? The negative predictive value represents the probability that the patient does not suffer from have the disease.This value is often influenced by the sensitivity, specificity, and prevalence in all cases.

? The positive likelihood ratio represents the probability of a patient who has the disease testing positive divided by the probability of a patient who does not have the disease testing positive.

? The negative likelihood ratio represents the probability of a patient who has the disease testing negative divided by the probability of a patient who does not have the disease testing negative.

? When the positive likelihood ratio is > 10 or the negative likelihood ratio is < 0.1, there is a significant increase in the probability that a ligament and tendon injury around the ankle exists or does not exist, respectively.

? The rate of correct diagnosis is calculated based on the following formula: [(the number of actual patients who are correctly diagnosed with a disease + the number of disease-free patients who are correctly diagnosed with no disease)/total number of patients] × 100%.

(2) The specificity and sensitivity, positive and negative predictive values, and positive and negative likelihood ratios of MUI of the femoral head for diagnosis of adult acetabular dysplasia as well as the rate of correct diagnosis.These measurement values are defined as described above.(3) The specificity and sensitivity, positive and negative predictive values, and positive and negative likelihood ratios of TBOI of the femoral head for diagnosis of adult acetabular dysplasia as well as the rate of correct diagnosis.These measurement values are defined as described above.(4) The correlation of OFI, MUI and TBOI to center-edge angle, Sharp angle and acetabular head index. The traditional acetabular dysplasia index is used to describe DDH.Compared with the traditional indicators (CE angle, Sharp angle and AHI), these three new radiological indicators,OFI, MUI and TBOI, are characterized by easier operation and easier selection of measurement landmarks on the radiographs of the hip.

(5) Risk factors for hip dysfunction as analyzed by logistic regression analyses. Hip Harris score as a dependent variable will be used to assess hip joint function of patients.16Harris hip score greater than 90 or notwill be used as an adjustment for hip joint function: > 90, good function; < 90, poor function. Independent variables include sex, age,OFI, MUI, TBOI, CE angle, Sharp angle, and AHI. Risk factors for hip dysfunction will be analyzed by logistic regression analyses.

Adverse events

Any adverse events related to radiological examination and diagnostic methods will be recorded, including expected or unexpected events (headache, nausea, fever). The date of occurrence, type of adverse events and therapeutic managements will be recorded.

Statistical analysis

Data will be statistically analyzed using SPSS 19.0 statistical software (IBM Corp., Armonk, NY, USA), following the intention-to-treat principle.

Count data will be expressed as percentages. Normally distributed measurement data will be expressed as means,standard deviations, min and max. Non-normally distributed data will be expressed as lower quartiles (q1),medians, and upper quartiles (q3).

The Mc Nemar test will be used to compare the sensitivity, specificity, positive and negative predictive values,positive and negative likelihood ratios, and rate of correct diagnosis of different radiological indicators for diagnosis of adult acetabular dysplasia at affected and healthy sides.

Receiver operating characteristic (ROC) curves will be created, and the optimal cut-off point will be selected as the diagnostic reference value. The ROC curve that is closer to the upper left corner indicates greater accuracy of the diagnosis. The area under the ROC curve will be taken as a measure of diagnostic accuracy.

Risk factors for hip dysfunction will be analyzed by logistic regression analyses. Correlation of different radiological indicators will be tested using Pearson or Spearman method.

A value of P < 0.05 is considered statistically significant.

Data collection and management

Clinical data will be collected on a case report form, recorded electronically, and saved in a dedicated computer.Only the researchers participating in the study will have the right to query the database, and any artificial modification or editing will not be allowed. All data will be permanently saved by the Third Hospital of Hebei Medical University.

Statistical analysis will be completed by professional statisticians, who will produce a statistical report. The statistical results will be given to the project manager,who will be responsible for writing the research report.

Ethics and dissemination

This study was approved by the Ethics Committee of the Third Hospital of Hebei Medical University with the approval No. KE2016-011-1. The trial will follow the relevant laws and regulations of the Declaration of Helsinki as well as the hospital’s relevant ethical principles. Manuscript preparation and editing were in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (Additional file 1). All the patients and their families will voluntarily participate in the trial, and give written informed consent with the premise of fully understanding the treatment plan. Anonymized trial data will be available at www.figshare.com.

TRIAL STATUS

In our pre-tests, anteroposterior X-ray data of the pelvis from 241 male patients showed that the OFI, MUI and TBOI were 86.8 ± 0.6%, 75.8 ± 2.0% and 76.2 ± 0.5%,which correlated with the CE angle, Sharp angle and AHI(Table 3).

DISCUSSION

Table 3: Correlation of radiological indicators in 241 male patients

Significance of the study

There are some divergences in the determination of important bone landmarks for radiological diagnosis of adult acetabular dysplasia. Moreover, measurement of relevant angles on the radiographs increases the possibility of error.

To improve the accuracy of diagnosis, three new indicators—OFI, MUI and TBOI of the femoral head—will be assessed in the diagnosis of adult acetabular dysplasia.

Limitations of the study

There is no normal control group in the study, which may affect the accuracy of the diagnostic results. Further investigation on the design of the trial is necessary.17-19

Novelty of the study

Based on the pre-test results, this study is expected to confirm the high sensitivity, specificity, and accuracy of the OFI, MUI and TBOI for diagnosis of adult acetabular dysplasia with a low rate of misdiagnosis.

Additional file

Additional file 1: SPIRIT checklist.

Author contributions

DQ conceived and designed the study, and also wrote the manuscript. Other authors will assist DQ to complete the trial. YTH

was responsible for manuscript review. All authors approved the final version of the manuscript for publication.

Conflicts of interest

The authors report no conflicts of interest in terms of research process and manuscript preparation.

Financial support

This study was financially supported by the Major Medical Research Project of Hebei Province in China (No. 20180457). The funder had no involvement in the study design; data collection,management, analysis, and interpretation; paper writing; or decision to submit the paper for publication.

Institutional review board statement

All protocols will be performed in accordance with the ethical principles of the Declaration of Helsinki. This trial has been approved by the Medical Ethics Committee of the Third Hospital of Hebei Medical University, China (approval number:KE2016-011-1).

Declaration of patient consent

The authors certify that they will obtain all appropriate patient or their legal guardian consent forms. In the form the patients or their legal guardians will give their consent for patients’ images and other clinical information to be reported in the journal. The patients will understand that their names and initials will not be published and due efforts will be made to conceal their identity,but anonymity cannot be guaranteed.

Reporting statement

This study follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidance for protocol reporting.

Biostatistics statement

The statistical methods of this study were reviewed by the biostatistician of the Third Hospital of Hebei Medical University, China.

Copyright transfer agreement

The Copyright License Agreement has been signed by all authors before publication.

Data sharing statement

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be in particular shared. Data of the present study,including study protocol and informed consent, will be available immediately following publication, no end date. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Anonymized trial data will be available indefinitely at www.figshare.com.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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