The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 91, Issue 5

Scientific Articles | May 01, 2009

Radiographic and Patient Factors Associated with Pre-Radiographic Osteoarthritis in Hip Dysplasia

Rebecca H. Jessel, BA¹; David Zurakowski, PhD¹; Christoph Zilkens, MD¹; Deborah Burstein, PhD²; Martha L. Gray, PhD³; Young-Jo Kim, MD, PhD¹

¹ Department of Orthopaedic Surgery, Children's Hospital Boston, Hunnewell 225, 300 Longwood Avenue, Boston, MA 02115. E-mail address for Y.-J. Kim: young-jo.kim@childrens.harvard.edu
² Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215
³ Harvard-MIT Division of Health Sciences and Technology, MIT E25-519, 77 Massachusetts Avenue, Cambridge, MA 02139

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Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Orthopaedic Research and Education Foundation (OREF). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Investigation performed at Children's Hospital, Boston, Massachusetts

The Journal of Bone and Joint Surgery, Inc.

J Bone Joint Surg Am, 2009 May 01;91(5):1120-1129. doi: 10.2106/JBJS.G.00144

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Abstract

Background: Hip dysplasia leads to abnormal loading of articular cartilage, which results in osteoarthritis. The purpose of this study was to investigate the anatomic and demographic factors associated with the early onset of osteoarthritis in dysplastic hips by utilizing the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index as a marker of the disease.

Methods: Ninety-six symptomatic dysplastic hips in seventy-four patients were assessed with standard radiographs and a dGEMRIC scan. The lateral center-edge angle of Wiberg, the acetabular index of Tönnis, and the break in the Shenton line were measured on a standing anteroposterior radiograph. Anterior undercoverage was assessed by measuring the anterior center-edge angle on a Lequesne false-profile view. A labral tear was considered to be present when contrast agent was seen through the entire thickness of the labrum on magnetic resonance arthrography. Osteoarthritis was defined as a dGEMRIC value of <390 msec (two standard deviations below the dGEMRIC index in normal hips).

Results: The mean dGEMRIC index (and standard deviation) for this cohort (473 ± 104 msec) was significantly lower than that of a morphologically normal hip (570 ± 90 msec). The anterior center-edge angle, the joint space width, and the presence of a labral tear were all found to be associated with osteoarthritis in the univariate analysis. Multivariate analysis identified age, the anterior center-edge angle, and the presence of a labral tear as independent factors associated with osteoarthritis. A second model was fitted with omission of the anterior center-edge angle because the lateral and anterior center-edge angles were highly correlated and the lateral center-edge angle is a more common clinical measure. This model identified age, the lateral center-edge angle, and the presence of a labral tear as significant independent factors associated with osteoarthritis.

Conclusions: As has been demonstrated in previous studies of the hip, this investigation showed osteoarthritis to be associated with increasing age and the severity of dysplasia, as demonstrated both by the Wiberg lateral center-edge angle and the Lequesne anterior center-edge angle. Additionally, we identified a labral tear as being a risk factor for osteoarthritis.

Level of Evidence: Prognostic Level III. See Instructions to Authors for a complete description of levels of evidence.

Figures in this Article

Introduction

Introduction | Materials and Methods | Results | Discussion | References

Clinical studies of patients with hip osteoarthritis suggest that underlying structural abnormalities result in accelerated or premature joint degradation^1-4. In patients with hip dysplasia, the characteristic shallow acetabulum leads to an increase in mechanical stress on the cartilage matrix, which can be beyond the physiologic level. The early onset of osteoarthritis in these hips is generally acknowledged to be due to the abnormal mechanics in the shallow acetabulum⁵. However, much is still not known about the patient demographic factors and structural characteristics of dysplastic hips that are associated with early osteoarthritis.

To our knowledge, Wiberg⁶ was the first to report an association between acetabular dysplasia and the development of hip osteoarthritis. He described the lateral center-edge angle as a measure of femoral head coverage by the acetabulum⁶ and defined a lateral center-edge angle of >25° as normal, 25° to 20° as borderline normal, and <20° as dysplastic and pathologic⁶. The association between acetabular dysplasia and the development of osteoarthritis was confirmed by Murphy et al., who showed that osteoarthritis developed by the seventh decade of life in all hips with moderate or severe dysplasia (a lateral center-edge angle of =15°)². Hence, osteoarthritis will eventually develop in hips with sufficiently severe dysplasia, but much is still not known about the onset of osteoarthritis.

Measurement of joint space width on conventional radiographs is the accepted method of determining the efficacy of treatment of osteoarthritis in clinical trials^7,8. Increasingly, magnetic resonance imaging is becoming the modality of choice because of its ability to directly image cartilage. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a technique that was designed to assess the biochemical properties of articular cartilage noninvasively. dGEMRIC is used to examine the fixed-negative-charge density of cartilage—i.e., the negatively charged glycosaminoglycans, which are lost early in the course of osteoarthritis⁹. Extensive in vitro and in vivo validation studies of this technique have been performed^10-16. In 2003, Kim et al.¹⁷ showed that the dGEMRIC index, as a measure of cartilage biochemical integrity, correlated with pain and the lateral center-edge angle in a clinically consistent manner. Therefore, dGEMRIC appears to be a more sensitive measure of early osteoarthritis than the classic osseous changes seen on standard radiographs¹⁷.

The purpose of this study was to determine if, by using a magnetic resonance imaging metric of osteoarthritis (the dGEMRIC index), rather than radiographic measures of osteoarthritis, we could further identify measurable anatomic and demographic factors that are associated with early osteoarthritis in dysplastic hips.

Materials and Methods

Introduction | Materials and Methods | Results | Discussion | References

Patient Selection

All patients who were diagnosed with developmental dysplasia of the hip by the senior author (Y.-J.K.) and had a clinical dGEMRIC scan between October 1999 and January 2006 were considered eligible for this retrospective study. Regardless of the severity of the symptoms, dysplasia, and radiographic signs of osteoarthritis, a dGEMRIC scan was performed to assess the cartilage and labral abnormalities. Institutional review board approval was obtained for this retrospective review.

All patients demonstrated skeletal maturity or near skeletal maturity (the triradiate cartilage was closing) in the hip. All had severe or moderate dysplasia but no evidence of a neuromuscular disorder or a skeletal dysplasia. In order to ensure that no "normal" hips were included, the cohort was restricted to hips that had a lateral center-edge angle of <16°. Hips with a prior acetabular osteotomy were excluded, but hips in which a prior reduction had been performed when the patient was an infant were included. Patients with other specific underlying hip disorders such as a fracture and Legg-Calvé-Perthes disease were also excluded.

Plain Radiographic Assessment

Ninety-six symptomatic hips in seventy-four patients were assessed with both plain radiographs and a dGEMRIC scan. The plain radiographs consisted of a standard standing anteroposterior pelvic radiograph made with the beam centered on the pubic symphysis as well as a false-profile view¹⁸ of the affected hip(s). The acetabular morphology was assessed on the standing anteroposterior radiograph by measuring the lateral center-edge angle of Wiberg, the acetabular index of Tönnis, and the break in the Shenton line¹⁹. The severity of the hip dysplasia was classified by measuring the lateral center-edge angle of Wiberg, with an angle of between 5° and 15° indicating moderate dysplasia and an angle of <5° indicating severe dysplasia.

The lateral center-edge angle is formed by the intersection of a line drawn through the center of the femoral head and extending to the lateral edge of the sourcil (the dense bone along the lateral edge of the weight-bearing region of the acetabulum) and a line perpendicular to one joining the two femoral head centers^2,6. The Tönnis angle²⁰ is formed by the intersection of a horizontal line connecting the femoral head centers and a line that passes through the medial edge of the sourcil. It is recorded to identify the tilt of the sourcil and the size of the weight-bearing zone. A break in the Shenton line (an imaginary line connecting the medial aspect of the femoral neck to the superior part of the pubic ramus) of >5 mm defined joint subluxation.

The false-profile view was used to record the anterior center-edge angle of Lequesne as a measurement of the anterior coverage of the femoral head¹⁸.

dGEMRIC Technique

The dGEMRIC scans were obtained with use of a GE Healthcare 1.5-T clinical scanner (Waukesha, Wisconsin). A double dose (0.4 mL/kg) of the U.S. Food and Drug Administration (FDA)-approved contrast agent Magnevist (gadolinium diethylenetriamine pentaacetic acid [Gd-DTPA^2-]; Berlex Laboratories, Wayne, New Jersey) was injected intravenously. The patients were required to walk thirty minutes after the injection, but prior to the scan, in order to ensure full penetration of the gadolinium into the articular cartilage¹³. A multislice fast-spin-echo sequence was used to obtain four coronal slices (saturation recovery technique; echo time, 14 msec; repetition time, 300, 500, 750, 1000, 1500, and 2000 msec). Each slice was 4 mm thick with 1-mm spacing between slices. A T1 map was obtained by fitting the saturation recovery curve to the varying image intensity as the repetition time was varied. Figure 1 illustrates an example of a dGEMRIC scan. The four coronal slices cover most of the weight-bearing surface of the hip joint. The dGEMRIC index was calculated as the average T1 value of the acetabular and femoral head cartilages in the weight-bearing zone (as designated from the edge of the acetabular rim to the indentation at the site of the attachment of the fovea to the femoral head) across all four coronal slices¹⁷. The scan in Figure 1 illustrates the normal zonal variation of fixed-charge density in articular cartilage.

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Fig. 1: Anteroposterior radiograph (left) and four coronal images (right) used to calculate the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index of a thirty-five-year-old woman with symptomatic dysplasia of the right hip. As seen on the radiograph, the right hip had a lateral center-edge angle of 7°. The color scale reflects the T1 relaxation time, which is proportional to the glycosaminoglycan (GAG) content of the cartilage; healthy cartilage with abundant glycosaminoglycan will be colored yellow. The femoral and acetabular cartilages of the weight-bearing area were identified, and the T1 values were averaged.

Magnetic Resonance Arthrography

An indirect arthrogram was used to detect labral tears. A labral tear was considered to be present when the contrast agent could be seen through the entire thickness of the labrum.

Statistical Analysis

We previously reported that the average dGEMRIC index (and standard deviation) for cartilage in nondysplastic hips (those with a lateral center-edge angle of >20°) without symptoms in patients with an average age of thirty-seven years was 570 ± 90 msec. Osteoarthritis was defined as an index of <390 msec, which is two standard deviations below the dGEMRIC index of healthy cartilage¹⁷. The validity of this cutoff is substantiated by our finding that the risk of failure after a pelvic osteotomy increases steeply for hips with a dGEMRIC index of <390 msec²¹.

Univariate analysis was used to compare cross-sectional data, including demographic and radiographic factors, between the twenty-two hips with substantial osteoarthritis (a dGEMRIC index of <390 msec) and the seventy-four with mild-to-no osteoarthritis. The unpaired Student t test was used to compare age between the two groups. Radiographic measurements including the lateral center-edge angle, anterior center-edge angle, Tönnis angle, and joint space width showed significant skewness (non-normality) as detected with the Kolmogorov-Smirnov test; therefore, the Mann-Whitney U test was used to compare these factors between groups and the values are presented as medians and ranges. The Pearson chi-square test was used to compare categorical and binary variables, such as the presence of subluxation and labral tears, between the two groups. Linear association between the anterior and lateral center-edge angles and the dGEMRIC index was determined for the younger age group (less than thirty years) and for the older age group (thirty years or older) with use of the Pearson product-moment correlation coefficient (r). A paired t test was used to compare the dGEMRIC indices on the two sides of individuals with bilateral dysplasia of similar severity—that is, in those in whom both hips were severely or moderately dysplastic. Multiple logistic regression was applied with use of backward selection and the likelihood ratio test to identify multivariate independent risk factors associated with significant arthritis in dysplastic hips²². The following six variables were tested: age, lateral center-edge angle, anterior center-edge angle, Tönnis angle, subluxation, and labral tear (Model I). A second model (Model II) was fit with omission of the anterior center-edge angle as a possible risk factor since the lateral center-edge angle and the anterior center-edge angle were highly correlated. Odds ratios and 95% confidence intervals were calculated for significant multivariate risk factors²³. Maximum likelihood estimation was used to derive the probability of osteoarthritis (a dGEMRIC index of <390 msec) based on the optimal set of risk factors. Two-tailed values of p < 0.05 were considered significant. The Hosmer-Lemeshow goodness-of-fit statistic was used to judge each model's quality of prediction²². In order to assess the results of our logisticregression models and to account for patients with bilateral disease (that is, two hips with dysplasia in the same patient), we used a generalized estimating equations approach as a kind of sensitivity analysis, with the hip as the repeated-measures factor and an independent working correlation structure. Since there are no likelihood ratio tests for generalized estimating equations, we used the Wald chi-square test with robust standard errors to assess the significance of the predictors of osteoarthritis and derived exponentiated regression coefficients (odds ratios) and corresponding 95% Wald confidence intervals²⁴.

Source of Funding

A portion of this study was funded by an Orthopaedic Research and Education Foundation research grant.

Results

Introduction | Materials and Methods | Results | Discussion | References

The demographics of this patient cohort (seventy-four patients with ninety-six involved hips) are presented in Table I. The mean dGEMRIC index (and standard deviation) was 473 ± 104 msec, which was significantly lower than the mean dGEMRIC index in morphologically normal hips (570 ± 90 msec)¹⁷ (p < 0.001). The dGEMRIC index was significantly higher in well-seated hips (those in which the Shenton line was intact) than it was in subluxated hips (p < 0.05). Additionally, the dGEMRIC index was significantly lower in the fifty-one older patients (thirty years old or more) than it was in the younger subgroup (p < 0.001). The dGEMRIC index positively correlated with the anterior center-edge angle in both the younger patients (r = 0.45, p = 0.003) and the older patients (r = 0.40, p = 0.006) (Figs. 2-A and 2-B). Similarly, the dGEMRIC index positively correlated with the lateral center-edge angle in both the younger patients (r = 0.42, p = 0.005) and the older patients (r = 0.31, p = 0.03) (Figs. 2-C and 2-D).

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Fig. 2-A: Scatterplot of the dGEMRIC index versus the severity of the dysplasia as measured by the anterior center-edge angle in forty-three patients younger than thirty years of age. The Pearson product-moment correlation coefficient (r) demonstrated a correlation between the dGEMRIC index and the anterior center-edge angle (r = 0.45, p = 0.003).

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Fig. 2-B: Scatterplot of the dGEMRIC index versus the severity of the dysplasia as measured by the anterior center-edge angle in forty-nine patients older than thirty years of age. The Pearson product-moment correlation coefficient (r) demonstrated a correlation between the dGEMRIC index and the anterior center-edge angle (r = 0.40, p = 0.006).

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Fig. 2-C: Scatterplot of the dGEMRIC index versus the severity of the dysplasia as measured by the lateral center-edge angle in forty-five patients younger than thirty years of age. The Pearson product-moment correlation coefficient (r) demonstrated a correlation between the dGEMRIC index and the lateral center-edge angle (r = 0.42, p = 0.005).

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Fig. 2-D: Scatterplot of the dGEMRIC index versus the severity of the dysplasia as measured by the lateral center-edge angle in fifty-one patients older than thirty years of age. The Pearson product-moment correlation coefficient (r) demonstrated a correlation between the dGEMRIC index and the lateral center-edge angle (r = 0.31, p = 0.03).

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TABLE I Univariate Comparisons of Demographic Characteristics and Imaging Findings According to the Severity of Osteoarthritis

	Severity of Osteoarthritis
Variable	dGEMRIC Index =390 msec (N = 74)	dGEMRIC Index <390 msec (N = 22)	Univariate Analysis P Value*
Age†(yr)	28.2 ± 10.4	32.3 ± 9.0	0.08‡
Sex (no. [%])
Female	63 (85)	18 (82)	0.71
Male	11 (15)	4 (18)
Radiographic measurements
Lateral center-edge angle§(deg)	7 (-36 to 15)	3 (-28 to 14)	0.09‡
Anterior center-edge angle§(deg)	4 (-47 to 38)	0 (-28 to 17)	0.04#
Tönnis angle§(deg)	25 (7 to 46)	27 (13 to 40)	0.54
Joint space width§(mm)	4 (2 to 7)	3 (0 to 7)	<0.001#
Subluxation (no. [%])	20 (27)	10 (45)	0.10‡
Magnetic resonance imaging
Presence of a labral tear (no. [%])	33 (45)	15 (68)	0.05#

Age was compared between groups with use of the Student t test. Radiographic center-edge and joint-space measurements were compared between groups with use of the Mann-Whitney U test. Categorical and binary variables were compared between groups with use of the Pearson chi-square test.The values are given as the mean and standard deviation.A statistical trend.The values are given as the median with the range in parentheses.A significant difference between the two groups.

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TABLE I Univariate Comparisons of Demographic Characteristics and Imaging Findings According to the Severity of Osteoarthritis

	Severity of Osteoarthritis
Variable	dGEMRIC Index =390 msec (N = 74)	dGEMRIC Index <390 msec (N = 22)	Univariate Analysis P Value*
Age†(yr)	28.2 ± 10.4	32.3 ± 9.0	0.08‡
Sex (no. [%])
Female	63 (85)	18 (82)	0.71
Male	11 (15)	4 (18)
Radiographic measurements
Lateral center-edge angle§(deg)	7 (-36 to 15)	3 (-28 to 14)	0.09‡
Anterior center-edge angle§(deg)	4 (-47 to 38)	0 (-28 to 17)	0.04#
Tönnis angle§(deg)	25 (7 to 46)	27 (13 to 40)	0.54
Joint space width§(mm)	4 (2 to 7)	3 (0 to 7)	<0.001#
Subluxation (no. [%])	20 (27)	10 (45)	0.10‡
Magnetic resonance imaging
Presence of a labral tear (no. [%])	33 (45)	15 (68)	0.05#

Twenty-two patients (forty-four hips) had bilateral dysplasia. Independent of the severity of the dysplasia of each hip, the dGEMRIC index did not differ significantly between the left and right hips in the same individual. Fourteen of the twenty-two patients had comparable severity in both hips; both hips were severely dysplastic in six of these patients, and both were moderately dysplastic in eight. Independent of the severity in the two hips (either moderate or severe), the dGEMRIC indices of the left and right hips were essentially equal (p = 0.97). For the eight individuals who had bilateral hip dysplasia of unequal severity, the mean difference in the dGEMRIC indices of the two hips was 52 msec; this difference was of a greater, but not a significantly greater, magnitude than that for the hips with comparable severity (p = 0.31).

Twenty-two (23%) of the ninety-six hips had a dGEMRIC index of <390 msec, indicative of osteoarthritis. In the univariate analysis, significant factors associated with a dGEMRIC index of <390 msec included the anterior center-edge angle (p = 0.04), joint space width (p < 0.001), and the presence of a labral tear (p = 0.05) (Table I).

With use of a dGEMRIC index of <390 msec as the cutoff value, multivariate logistic regression analysis was performed to identify significant independent risk factors of early osteoarthritis, and the results were compared with those derived with use of a generalized estimating equations approach to handle patients with bilateral disease (Table II). In Model I, the following six variables were tested: age, lateral center-edge angle, anterior center-edge angle, Tönnis angle, subluxation, and presence of a labral tear. The significant risk factors included age (p = 0.03), anterior center-edge angle (p < 0.01), and presence of a labral tear (p = 0.01). In Model II, the anterior center-edge angle was omitted as a candidate since that angle is highly correlated with the lateral center-edge angle (r = 0.76, p < 0.001). The significant variables in Model II were age (p = 0.03), lateral center-edge angle (p < 0.01), and the presence of a labral tear (p = 0.03).

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TABLE II Results of Multivariate Analyses to Determine Independent Predictors of Substantial Osteoarthritis

Variable	Likelihood Ratio Test	Odds Ratio	95% Confidence Interval	P Value*
Model I
Age	4.8	1.07	1.01-1.12	0.03†
Lateral center-edge angle				0.78
Anterior center-edge angle	7.9	0.94	0.91-0.98	<0.01†
Tönnis angle				0.31
Subluxation				0.52
Presence of a labral tear	6.3	4.22	1.54-11.55	0.01†
Model II
Age	4.6	1.07	1.01-1.12	0.03†
Lateral center-edge angle	6.7	0.94	0.89-0.98	<0.01†
Tönnis angle				0.45
Subluxation				0.40
Presence of a labral tear	4.5	3.28	1.25-8.62	0.03†

Based on multiple stepwise logistic regression analysis (backward selection).Significant independent predictor of osteoarthritis.

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TABLE II Results of Multivariate Analyses to Determine Independent Predictors of Substantial Osteoarthritis

Variable	Likelihood Ratio Test	Odds Ratio	95% Confidence Interval	P Value*
Model I
Age	4.8	1.07	1.01-1.12	0.03†
Lateral center-edge angle				0.78
Anterior center-edge angle	7.9	0.94	0.91-0.98	<0.01†
Tönnis angle				0.31
Subluxation				0.52
Presence of a labral tear	6.3	4.22	1.54-11.55	0.01†
Model II
Age	4.6	1.07	1.01-1.12	0.03†
Lateral center-edge angle	6.7	0.94	0.89-0.98	<0.01†
Tönnis angle				0.45
Subluxation				0.40
Presence of a labral tear	4.5	3.28	1.25-8.62	0.03†

Based on multiple stepwise logistic regression analysis (backward selection).Significant independent predictor of osteoarthritis.

Given the important association of age, the lateral center-edge angle, and the presence of a labral tear with a low dGEMRIC index, a maximum likelihood estimation in a logistic regression analysis was used to determine the probability of osteoarthritis (a dGEMRIC index of <390 msec) on the basis of age (a continuous variable), the severity of the dysplasia (based on a cutoff value, with a lateral center-edge angle of 5° to 15° indicating moderate dysplasia and a lateral center-edge angle of <5° indicating severe dysplasia), and the presence or absence of a labral tear. The curves in Figure 3 represent the probabilities of osteoarthritis for each risk group as a function of increasing age. A look-up table provides combinations of risk factors for patients fifteen to fifty years of age (Table III).

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Fig. 3: Probability of osteoarthritis (OA) developing as a function of age in moderately and severely dysplastic hips (as indicated by the lateral center-edge angle) with and without a labral tear.

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TABLE III Probability of Substantial Osteoarthritis Based on Multivariate Predictors*

	No Labral Tear			Labral Tear
Age (yr)	Lateral Center-Edge Angle 5°-15° (Moderate Dysplasia)	Lateral Center-Edge Angle <5° (Severe Dysplasia)	Lateral Center-Edge Angle 5°-15° (Moderate Dysplasia)	Lateral Center-Edge Angle <5° (Severe Dysplasia)
15	6	11	13	23
20	7	14	16	28
25	9	17	20	33
30	11	20	24	38
35	14	24	28	44
40	17	29	33	50
45	21	34	38	55
50	25	39	44	61

Substantial osteoarthritis was defined as a dGEMRIC index of <390 msec. The data in each column represent the predicted probability of substantial osteoarthritis and are expressed as percentages. Probabilities were derived from the final multivariate logistic regression analysis (Model II).

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TABLE III Probability of Substantial Osteoarthritis Based on Multivariate Predictors*

	No Labral Tear			Labral Tear
Age (yr)	Lateral Center-Edge Angle 5°-15° (Moderate Dysplasia)	Lateral Center-Edge Angle <5° (Severe Dysplasia)	Lateral Center-Edge Angle 5°-15° (Moderate Dysplasia)	Lateral Center-Edge Angle <5° (Severe Dysplasia)
15	6	11	13	23
20	7	14	16	28
25	9	17	20	33
30	11	20	24	38
35	14	24	28	44
40	17	29	33	50
45	21	34	38	55
50	25	39	44	61

The statistic that is most often used to judge model adequacy and the quality of prediction based on the logistic regression analysis is the Hosmer-Lemeshow goodness-of-fit chi-square statistic (C). Low R² values in logistic regression are the norm, and experts do not recommend reporting R² values with results from fitted logistic regression models²². We calculated the Hosmer-Lemeshow goodness-of-fit statistic for each of our final multivariate logistic regression models for identifying osteoarthritis. In Model I, the Hosmer-Lemeshow chi-square was 9.517 on eight degrees of freedom (p = 0.30). In Model II, it was 13.896 on eight degrees of freedom (p = 0.09). Thus, our fitted regression models, based on the three clinical risk factors (age, labral tear, and anterior center-edge angle/lateral center-edge angle), were judged to be high-quality models according to the Hosmer-Lemeshow measure of goodness-of-fit statistic.

To take into account the twenty-two patients with bilateral disease (both hips evaluated for each patient) and to verify the results of our multivariate logistic regression Models I and II, we applied a generalized estimating equations strategy with use of a binomial distribution and a logit link function. On the basis of Wald chi-square tests, Model I was verified with use of the generalized estimating equations approach, which yielded the same three risk factors: age (Wald test = 4.41, p = 0.036, odds ratio = 1.06, 95% confidence interval = 1.02 to 1.12), anterior center-edge angle (Wald test = 7.02, p < 0.01, odds ratio = 0.94, 95% confidence interval = 0.90 to 0.98), and the presence of a labral tear (Wald test = 6.95, p < 0.01, odds ratio = 4.94, 95% confidence interval = 1.51 to 16.22). Additionally, generalized estimating equations modeling confirmed the results of the multivariate logistic regression analysis for Model II with the following three risk factors for osteoarthritis: age (Wald test = 4.24, p = 0.039, odds ratio = 1.07, 95% confidence interval = 1.01 to 1.14), lateral center-edge angle (Wald test = 5.51, p = 0.019, odds ratio = 0.94, 95% confidence interval = 0.89 to 0.99), and the presence of a labral tear (Wald test = 5.30, p < 0.01, odds ratio = 3.63, 95% confidence interval = 1.23 to 10.90).

Discussion

Introduction | Materials and Methods | Results | Discussion | References

At present, the clinical definition of osteoarthritis is based on plain radiographic findings, which only become evident later in the disease process; there are no clear magnetic resonance imaging criteria for the diagnosis of osteoarthritis. The dGEMRIC index has been shown to correlate with patient symptoms and to be a good predictor of the outcome of osteotomy for the treatment of hip dysplasia, with both findings suggesting that the index is a valid measure of joint degeneration^17,21.

The results of the current study are consistent with the conclusion by Murphy et al.² that osteoarthritis will eventually develop in hips with a lateral center-edge angle of less than approximately 15°. All of our subjects had a lateral center-edge angle of <16°, and the average dGEMRIC index in the entire cohort was significantly lower than the normal range. Additionally, the severity of the dysplasia correlated with early osteoarthritis. Furthermore, early osteoarthritis appears to be more highly associated with anterior acetabular deficiency than it is with lateral acetabular deficiency (Table II). This finding is consistent with the observation, in patients with hip dysplasia, that the damage from undercoverage is often most severe in the anterior portion of the joint²⁵. These findings are also consistent with the results of a thirty-year-follow-up study of patients with hip dysplasia by Hadley et al.²⁶. Those authors found that a cumulative over-pressure index, which is a measure of the cumulative amount of time that a hip experiences abnormal mechanical stress, correlates with the development of hip osteoarthritis. Their finding is in agreement with our observations that patient age and the severity of the dysplasia were associated with early osteoarthritis.

In addition to the osseous acetabulum, the labrum acts as a stabilizer of the femoral head in the acetabulum. The labrum plays a key role in providing supplemental support to dysplastic hips and in compensating for the stability lost as a result of the shallow acetabulum. Therefore, if the labrum tears, additional stress is placed on the adjacent articular cartilage. Our results support this hypothesis; more severe osteoarthritis was present in hips with a labral tear. Whether a labral tear is a direct contributing factor to osteoarthritis or is secondary to osteoarthritis is a question that has yet to be answered. However, given the already altered biochemical and mechanical environment in dysplastic hips, a labral tear seems to be a compounding factor in the progression of osteoarthritis.

Even at a young age, severely dysplastic hips (a lateral center-edge angle of <5°) become osteoarthritic, and the osteoarthritis will continue to worsen over time. As expected, the lowest dGEMRIC index was seen in older individuals with severe dysplasia in our series. Additionally, in concurrence with the findings reported by Cooperman et al.²⁷, joint subluxation was associated with increased osteoarthritis.

The mechanism leading to the onset of premature osteoarthritis in dysplastic hips is a function of increased joint stress and pressure. The dysplastic acetabulum leads to a reduced load-transferring area, which concentrates the impact of normal forces on the articular cartilage. The damage to the cartilage due to these excessive stresses accumulates with time. Eventually, signs of osteoarthritis will develop in any joint that has been subjected to such overloading and instability. Joint-preservation operations such as periacetabular osteotomy possess the potential to reverse the disease process of osteoarthritis²⁸. Cunningham et al. demonstrated that dGEMRIC is a useful tool with which to identify good candidates for surgery²¹. The best predictor of early failure after pelvic osteotomy for hip dysplasia was the dGEMRIC index, with the risk of early failure increasing steeply for hips with a dGEMRIC index of <390 msec. This technique also has the potential to demonstrate the disease-modifying potential of pelvic osteotomy for hip dysplasia by allowing the identification of hips with early osteoarthritis before permanent structural changes to cartilage have occurred and by making it possible to demonstrate the restoration of cartilage matrix components with improved mechanics after surgery.

The dGEMRIC technique is relatively straightforward to implement with the use of standard magnetic resonance imaging equipment, and patients tolerate the scan well. Magnevist is a commonly used, readily available, FDA-approved contrast agent employed in magnetic resonance imaging. Currently, its broader acceptance is limited by a long scan time and the need for post-processing to calculate the T1 maps. At present, fast T1-mapping sequences with in-line T1-mapping software allows this useful cartilage-imaging technique to be widely applicable in the clinical setting²⁹.

We identified patient age, the severity of the dysplasia as indicated by the anterior center-edge angle or the lateral center-edge angle, and the presence of a labral tear as factors associated with clinically relevant osteoarthritis. However, the analysis in this study was performed retrospectively on a cross-sectional cohort; hence, this is not a natural history study. Nevertheless, we believe that this report provides clinically meaningful information and also demonstrates that clinical studies of osteoarthritis can be performed with use of more sensitive metrics such as dGEMRIC, rather than radiographs. In the near future, we hope to develop a concrete prediction model by performing a prospective follow-up study. Image Not Available

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Introduction | Materials and Methods | Results | Discussion | References

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Topics

hip dislocation, congenital ; osteoarthritis ; dysplasia ; gadolinium-enhanced magnetic resonance imaging of cartilage

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Rebecca H. Jessel, David Zurakowski, Christoph Zilkens, Deborah Burstein, Martha L. Gray, Young-Jo Kim; Radiographic and Patient Factors Associated with Pre-Radiographic Osteoarthritis in Hip Dysplasia. The Journal of Bone & Joint Surgery. 2009 May;91(5):1120-1129.

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