Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calvé-Perthes Disease?

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a childhood hip disease characterized by osteonecrosis of the femoral head. Because severe deformity of the femoral head can cause secondary osteoarthritis in adulthood, progressive collapse should be prevented in children with a necrotic epiphysis. The prognosis of patients with LCPD generally worsens as the age at disease onset increases, and the appropriate treatment for late-onset LCPD remains unclear. Based on the limited effect of nonoperative treatment using a nonweightbearing brace, flexion varus osteotomy (FVO) was introduced in 2010 as an initial treatment for late-onset LCPD in place of brace treatment, which we used in our institution before that time. QUESTIONS/PURPOSES: We asked, (1) Which treatment, FVO or a nonweightbearing brace, is associated with a lower likelihood of progressive femoral head collapse in children whose diagnosis of LCPD was made at the age of ≥ 8 years and who were followed for a minimum of 3 years after their intervention? (2) What proportion of patients in the brace group had surgery despite the treatment, and what percentage of children in the FVO group had a second operation to remove hardware and/or additional operations? METHODS: The initial treatment was applied in 181 patients with LCPD between 1995 and 2018 in our institution. Patients whose disease onset was at ≥ 8 years old (late-onset LCPD) with complete clinical and radiologic data were considered potentially eligible. In 2010, treatment for these patients changed from brace treatment to FVO for all patients. A total of 35% (42 of 121) of patients who were treated with a nonweightbearing brace between 1995 and 2009 and 40% (24 of 60) of patients who were treated with FVO between 2010 and 2018 were eligible. Among patients treated with a brace, 21% (nine of 42 patients) were excluded because of hospital transfer (three patients), short-term follow-up (three), the period from onset to the first visit was ≥ 7 months (two), and inability to use the brace because of mental incapacity (one patient). In patients treated with FVO, 12% (three of 24 patients) were excluded (two patients with a period from onset to the first visit ≥ 7 months and one with a comorbidity and multiple-epiphyseal dysplasia). Among the remaining patients, 79% (33 of 42 patients) were classified into the brace group and 88% (21 of 24 patients) were classified into the FVO group for analyses. There were no overlapping patients at the timepoint when the treatment strategy for late-onset LCPD changed. In the FVO group, subtrochanteric osteotomy with 35° to 40° of flexion and 15° to 20° of varus was performed using a locking compression plate for pediatric use. Patient demographics, radiographic parameters, and the assessment of femoral head deformity using the Stulberg classification were compared between the two groups. There was a greater proportion of boys than girls in both groups (brace: 88% and FVO: 86%), and there were no differences in the distribution of genders between the groups (p = 0.82). The right side was more frequently treated in the brace group, but there was no difference in laterality between the groups (brace: 58% right and FVO: 62% left; p = 0.16). There was no difference between groups in the median age at disease onset (9.0 years [range 8.0 to 12.5 years] in the brace group and 9.6 years [range 8.0 to 12.4 years] in the FVO group; p = 0.26). There was no difference between the groups in the period of treatment from onset (1.7 ± 1.9 months in the brace group and 1.5 ± 1.5 months in the FVO group; p = 0.73) or the follow-up period (6.7 ± 2.1 years in the brace group and 6.2 ± 2.1 years in the FVO group; p = 0.41). The LCPD stage at the first visit was assessed using the modified Waldenström classification. The intraobserver and interobserver values of the modified Waldenström classification, evaluated using kappa statistics, were excellent (kappa value 0.89 [95% CI 0.75 to 0.97]; p < 0.01) and good (kappa value 0.65 [95% CI 0.43 to 0.87]; p < 0.01). The radiographic degree of collapse at the maximum fragmentation stage was assessed using the lateral pillar classification. The intraobserver and interobserver reliabilities of the lateral pillar classification were excellent (kappa value 0.84 [95% CI 0.73 to 0.94]; p < 0.01) and excellent (kappa value 0.83 [95% CI 0.71 to 0.94]; p < 0.01). The degree of femoral head deformity at the most recent follow-up examination was compared between the groups in terms of the Stulberg classification, in which Classes I and II were classified as good and Classes III through V were classified as poor. The intraobserver and interobserver reliabilities of the Stulberg classification were good (kappa value 0.74 [95% CI 0.55 to 0.92]; p < 0.01) and good (kappa value 0.69 [95% CI 0.50 to 0.89]; p < 0.01). The evaluators were involved in the patients' clinical care as part of the treating team. RESULTS: Good radiographic results (Stulberg Class I or II) were obtained more frequently in the FVO group (76% [16 of 21 patients]) than in the brace group (36% [12 of 33 patients]), with an odds ratio of 5.6 (95% CI 1.7 to 18.5; p < 0.01). In the brace group, a subsequent femoral varus osteotomy was performed in 18% (six of 33) of patients with progressive collapse and hinge abduction, and implant removal surgery was performed approximately 1 year after the first procedure. This traditional varus osteotomy was occasionally performed in patients who were considered for conversion from nonoperative treatment before 2009 because FVO had not yet been introduced. In the FVO group, all patients (n = 21) had a second procedure to remove the implant at a mean of 10.5 ± 1.2 months postoperatively. Additional procedures were performed in 24% (five of 21) of patients, including a second FVO for progressive collapse (one patient), guided growth for a limb length discrepancy (one patient), and flexion valgus osteotomy for coxa vara in patients with a limb length discrepancy (three patients). CONCLUSION: Our historical control study found that FVO may increase the possibility of obtaining good radiographic results (Stulberg Class I or II) compared with brace treatment for patients with late-onset LCPD, although surgical interventions after the first and second implant removal procedures may be indicated. Surgeons can consider FVO if they encounter patients with late-onset LCPD, which is a challenging condition. A larger study with long-term follow-up is needed to confirm the efficacy of FVO. LEVEL OF EVIDENCE: Level III, therapeutic study.

Effect of coronal plane acetabular correction on joint contact pressure in Periacetabular osteotomy: a finite-element analysis.

BACKGROUND: The ideal acetabular position for optimizing hip joint biomechanics in periacetabular osteotomy (PAO) remains unclear. We aimed to determine the relationship between acetabular correction in the coronal plane and joint contact pressure (CP) and identify morphological factors associated with residual abnormal CP after correction. METHODS: Using CT images from 44 patients with hip dysplasia, we performed three patterns of virtual PAOs on patient-specific 3D hip models; the acetabulum was rotated laterally to the lateral center-edge angles (LCEA) of 30°, 35°, and 40°. Finite-element analysis was used to calculate the CP of the acetabular cartilage during a single-leg stance. RESULTS: Coronal correction to the LCEA of 30° decreased the median maximum CP 0.5-fold compared to preoperatively (p <  0.001). Additional correction to the LCEA of 40° further decreased CP in 15 hips (34%) but conversely increased CP in 29 hips (66%). The increase in CP was associated with greater preoperative extrusion index (p = 0.030) and roundness index (p = 0.038). Overall, virtual PAO failed to normalize CP in 11 hips (25%), and a small anterior wall index (p = 0.049) and a large roundness index (p = 0.003) were associated with residual abnormal CP. CONCLUSIONS: The degree of acetabular correction in the coronal plane where CP is minimized varied among patients. Coronal plane correction alone failed to normalize CP in 25% of patients in this study. In patients with an anterior acetabular deficiency (anterior wall index < 0.21) and an aspherical femoral head (roundness index > 53.2%), coronal plane correction alone may not normalize CP. Further studies are needed to clarify the effectiveness of multiplanar correction, including in the sagittal and axial planes, in optimizing the hip joint's contact mechanics.

Is Anterior Rotation of the Acetabulum Necessary to Normalize Joint Contact Pressure in Periacetabular Osteotomy? A Finite-element Analysis Study.

BACKGROUND: Inappropriate sagittal plane correction can result in an increased risk of osteoarthritis progression after periacetabular osteotomy (PAO). Individual and postural variations in sagittal pelvic tilt, along with acetabular deformity, affect joint contact mechanics in dysplastic hips and may impact the direction and degree of acetabular correction. Finite-element analyses that account for physiologic pelvic tilt may provide valuable insight into the effect of PAO on the contact mechanics of dysplastic hips, which may lead to improved acetabular correction during PAO. QUESTIONS/PURPOSES: We performed virtual PAO using finite-element models with reference to the standing pelvic position to clarify (1) whether lateral rotation of the acetabulum normalizes the joint contact pressure, (2) risk factors for abnormal contact pressure after lateral rotation of the acetabulum, and (3) whether additional anterior rotation of the acetabulum further reduces contact pressure. METHODS: Between 2016 and 2020, 85 patients (92 hips) underwent PAO to treat hip dysplasia. Eighty-two patients with hip dysplasia (lateral center-edge angle < 20°) were included. Patients with advanced osteoarthritis, femoral head deformity, prior hip or spine surgery, or poor-quality images were excluded. Thirty-eight patients (38 hips) were eligible to participate in this study. All patients were women, with a mean age of 39 ± 10 years. Thirty-three women volunteers without a history of hip disease were reviewed as control participants. Individuals with a lateral center-edge angle < 25° or poor-quality images were excluded. Sixteen individuals (16 hips) with a mean age of 36 ± 7 years were eligible as controls. Using CT images, we developed patient-specific three-dimensional surface hip models with the standing pelvic position as a reference. The loading scenario was based on single-leg stance. Four patterns of virtual PAO were performed in the models. First, the acetabular fragment was rotated laterally in the coronal plane so that the lateral center-edge angle was 30°; then, anterior rotation in the sagittal plane was added by 0°, 5°, 10°, and 15°. We developed finite-element models for each acetabular position and performed a nonlinear contact analysis to calculate the joint contact pressure of the acetabular cartilage. The normal range of the maximum joint contact pressure was calculated to be < 4.1 MPa using a receiver operating characteristic curve. A paired t-test or Wilcoxon signed rank test with Bonferroni correction was used to compare joint contact pressures among acetabular positions. We evaluated the association of joint contact pressure with the patient-specific sagittal pelvic tilt and acetabular version and coverage using Pearson or Spearman correlation coefficients. An exploratory univariate logistic regression analysis was performed to identify which of the preoperative factors (CT measurement parameters and sagittal pelvic tilt) were associated with abnormal contact pressure after lateral rotation of the acetabulum. Variables with p values < 0.05 (anterior center-edge angle and sagittal pelvic tilt) were included in a multivariable model to identify the independent influence of each factor. RESULTS: Lateral rotation of the acetabulum decreased the median maximum contact pressure compared with that before virtual PAO (3.7 MPa [range 2.2-6.7] versus 7.2 MPa [range 4.1-14 MPa], difference of medians 3.5 MPa; p < 0.001). The resulting maximum contact pressures were within the normal range (< 4.1 MPa) in 63% of the hips (24 of 38 hips). The maximum contact pressure after lateral acetabular rotation was negatively correlated with the standing pelvic tilt (anterior pelvic plane angle) (ρ = -0.52; p < 0.001) and anterior center-edge angle (ρ = -0.47; p = 0.003). After controlling for confounding variables such as the lateral center-edge angle and sagittal pelvic tilt, we found that a decreased preoperative anterior center-edge angle (per 1°; odds ratio 1.14 [95% CI 1.01-1.28]; p = 0.01) was independently associated with elevated contact pressure (≥ 4.1 MPa) after lateral rotation; a preoperative anterior center-edge angle < 32° in the standing pelvic position was associated with elevated contact pressure (sensitivity 57%, specificity 96%, area under the curve 0.77). Additional anterior rotation further decreased the joint contact pressure; the maximum contact pressures were within the normal range in 74% (28 of 38 hips), 76% (29 of 38 hips), and 84% (32 of 38 hips) of the hips when the acetabulum was rotated anteriorly by 5°, 10°, and 15°, respectively. CONCLUSION: Via virtual PAO, normal joint contact pressure was achieved in 63% of patients by normalizing the lateral acetabular coverage. However, lateral acetabular rotation was insufficient to normalize the joint contact pressure in patients with more posteriorly tilted pelvises and anterior acetabular deficiency. In patients with a preoperative anterior center-edge angle < 32° in the standing pelvic position, additional anterior rotation is expected to be a useful guide to normalize the joint contact pressure. CLINICAL RELEVANCE: This virtual PAO study suggests that biomechanics-based planning for PAO should incorporate not only the morphology of the hip but also the physiologic pelvic tilt in the weightbearing position in order to customize acetabular reorientation for each patient.

Effect of sagittal pelvic tilt on joint stress distribution in hip dysplasia: A finite element analysis.

BACKGROUND: Physiologic pelvic tilt can change acetabular orientation and coverage in patients with hip dysplasia. In this study, we aimed to clarify the impact of change in sagittal pelvic tilt on joint stress distribution in dysplastic hips. METHODS: We developed patient-specific finite element models of 21 dysplastic hips and 21 normal hips. The joint contact area, contact pressure, and equivalent stress of the acetabular cartilage were assessed at three pelvic tilt positions relative to the functional pelvic plane: 10° anterior tilt, no tilt, and 10° posterior tilt. FINDINGS: The mean contact area was 0.6-0.7 times smaller, the mean maximum contact pressure was 1.8-1.9 times higher, and the mean maximum equivalent stress was 1.3-2.8 times higher in dysplastic hips than in normal hips at all three pelvic positions. As the pelvis tilted from 10° anterior to 10° posterior, the mean contact area decreased, and the mean maximum contact pressure and median maximum equivalent stress increased. The latter two changes were more significant in dysplastic hips than in normal hips (total increment was 1.3 MPa vs. 0.4 MPa, P = 0.001, and 3.6 MPa vs. 0.4 MPa, P < 0.001, respectively). The mean equivalent stress increased in the anterosuperior acetabulum during posterior pelvic tilt in dysplastic and normal hips, while the change was not significant in the superior and posterosuperior acetabulum in both groups. INTERPRETATION: Sagittal pelvic tilt alters the loading environment and joint stress distribution of the hip joint and may impact the degeneration process in dysplastic hips.

Is lateral acetabular rotation sufficient to correct anterolateral deficiency in periacetabular reorientation osteotomy? A CT-Based simulation study.

BACKGROUND: Residual acetabular deficiency after periacetabular reorientation osteotomy can result in suboptimal outcome. The optimal algorithm of acetabular fragment correction to achieve normal anterolateral acetabular coverage is not well characterized. The aim of this study was to determine the prevalence of residual anterolateral deficiency after lateral acetabular rotation and to evaluate the ability of additional sagittal and axial rotation of the acetabulum to normalize the acetabular coverage in periacetabular osteotomy. METHODS: We performed computed tomography-based simulated periacetabular osteotomy on 85 patients (85 hips) with hip dysplasia. The acetabular fragment was rotated laterally to achieve a lateral center-edge angle (CEA) of 30°. For hips with residual anterolateral deficiency, which were identified based on the reference interval of the anterior CEA, the acetabulum was further rotated in the sagittal or axial direction in 5-degree increments from 5° to 20°, and the ability of these two manoeuvres to restore a normal anterior CEA was assessed. RESULTS: After lateral acetabular rotation, 16 hips (19%) had residual anterolateral deficiency, 67 hips (79%) had normal acetabular coverage, and 2 hips (2.4%) had acetabular overcoverage. A preoperative anterior CEA <37° predicted residual deficiency (sensitivity, 94%; specificity, 81%). Additional anterior sagittal rotation was more effective than posterior axial rotation in normalizing the anterior CEA, while minimizing the decrease in posterior CEA. The highest number of hips with normal anterior and posterior CEA was noted at 10° sagittal rotation (81%), which was followed by 15° sagittal rotation (63%). CONCLUSIONS: Normal anterolateral coverage was achieved in 79% of patients after rotating the acetabulum laterally. However, lateral rotation of the acetabulum may be insufficient to correct the anterolateral deficiency in patients with an anterior CEA of <37°. In them, additional 10°-15° anterior sagittal rotation may be appropriate to achieve sufficient anterolateral coverage while retaining posterolateral coverage.

Acetabular retroversion in dysplastic hips is associated with decreased 3D femoral head coverage independently from lateral center-edge angle.

INTRODUCTION: The clinical significance of acetabular retroversion in non-dysplastic hips can be explained as pincer-type femoroacetabular impingement (FAI), whereas that in dysplastic hips is not clarified because FAI normally poses little problems for dysplastic hips. We aimed to evaluate three-dimensional (3D) femoral head coverage in dysplastic hips with and without acetabular retroversion and to elucidate the role of acetabular retroversion on the 3D femoral head coverage. MATERIALS AND METHODS: We retrospectively investigated 93 hips in 93 patients (9 males and 84 females) that underwent periacetabular osteotomy for hip dysplasia. Dysplastic hips were divided into anteversion and retroversion groups according to their cranial anteversion, which was measured on the axial section 5 mm caudal to the acetabular roof. The 3D femoral head coverage was provided as a percentage of the acetabulum-covered surface area of the upper femoral hemisphere using a 3D preoperative planning software for total hip arthroplasty. RESULTS: Of the 93 dysplastic hips, 15 hips (16%) were assigned to the retroversion group, which had significantly younger age at surgery (31.9 years versus 39.2 years; p = 0.033). The lateral center-edge angles were comparable between the groups (13.8° versus 12.9°; p = 0.68); however, the hips in the retroversion group had a trend of smaller 3D femoral head coverage than those in the anteversion group (59% versus 63%; p = 0.058). Multivariate analysis using two-way analysis of covariance showed that lateral center-edge angle (partial regression coefficient = 0.83; t value = 17.3; p < 0.001) and acetabular retroversion (partial regression coefficient = - 2.3; t value = - 4.9; p < 0.001) were independent factors that contributed to the 3D femoral head coverage. CONCLUSIONS: Acetabular retroversion in dysplastic hips was associated with decreased 3D femoral head coverage independently from lateral center-edge angle. The age at surgery in the retroversion group was significantly younger, suggesting a relationship between decreased 3D coverage and potentially earlier symptom onset.

How does anteroposterior cup placement affect bone coverage and range of motion in primary total hip arthroplasty for hip dysplasia?

BACKGROUND: Due to anterior bone defects, high and/or posterior placement of an acetabular cup is often required to achieve sufficient coverage in patients with hip dysplasia. We examined whether posterior cup placement affected the postoperative range of motion (ROM) in primary total hip arthroplasty (THA). METHODS: Using computer software, bone coverage and ROM were examined in 32 patients with unilateral osteoarthritis of the hip with Crowe type II or III hip dysplasia. We determined the cup position to satisfy cup center-edge (Cup-CE) angle ≥0° and the required ROM. The cup was placed at the anatomic hip center and moved in 2-mm increments anteroposteriorly and 10-mm increments vertically. RESULTS: At vertical anatomic hip center, less than 68.8% hips fulfilled Cup-CE ≥0° regardless of anteroposterior position. Significantly more hips at higher hip center with posterior cup placement achieved Cup-CE ≥0° than hips at vertical anatomic hip center, and 10 mm higher hip center was the most suitable for achieving bone coverage. However, posterior and superior cup placement significantly decreased the flexion and IR due to early bone impingement, whereas ER and extension were not affected. A smoothing spline curve demonstrated that more posterior cup placement than 4.8 mm and 3.6 mm did not satisfy the required ROM at 10 mm and 20 mm higher hip center, respectively. CONCLUSIONS: Posterosuperior cup placement gained more bone coverage but decreased the range of hip flexion and internal rotation. Consequently, posterosuperior cup placement did not satisfy the required ROM.

Clinical outcomes of conservative treatment with a non-weight-bearing abduction brace for Legg-Calvé-Perthes disease.

BACKGROUND: Treatment with a brace is the first choice as conservative treatment via the containment method for Legg-Calvé-Perthes disease (LCPD). The purpose of this study is to evaluate clinical outcomes and influential factors of conservative treatment with the non-weight-bearing abduction brace for LCPD. METHODS: One hundred thirty hips in 130 patients were examined in this study. The mean age at onset was 7.0 years (3.3-12.4 years) and the mean follow-up period was 8.4 years (4.1-17.6 years). The extent of necrosis and lateral collapse of the femoral head were evaluated using the Catterall classification and the lateral pillar classification, respectively. Radiological outcome was assessed as good (classes I and II), fair (III), and poor (IV), according to the modified Stulberg classification. RESULTS: Radiographic outcome at final follow-up was good in 82 hips (63%), fair in 40 hips (31%), and poor in 8 hips (6%). Multinomial logistic regression analysis showed that major influential factors for good outcomes were as follows: age at onset, lateral pillar classification, and Catterall classification. From the receiver operating characteristic curve, the cut-off value for age at onset was 8.4 years old to obtain good outcomes. Hips with Catterall group I and II and lateral pillar group A and B had significantly better results. CONCLUSION: Patients younger than 8.4 years old at onset with lateral pillar group A or B or Catterall group I or II showed good outcomes with a non-weight-bearing abduction brace for LCPD. These results show that alternative treatment, such as surgery, may be another option for patients who are not included in the above groups.

Long-Term Stability of a Cellulose-Based Glucose Oxidase Membrane.

A cellulose-based glucose oxidase membrane was prepared on a glassy carbon (GC) electrode. The current response of the electrode to glucose was measured by applying a potential of 1.0 V vs. Ag/AgCl on the base GC and was proportional to the concentration of glucose up to 1 mM. The long-term stability of the electrode was examined by measuring the daily glucose response. Over four months, the response magnitude was maintained and then gradually decreased. After 11 months, though the response magnitude decreased to 50% of the initial value, the linear response range did not change. Therefore, the electrode could be used as a glucose biosensor even after 11 months of use. The entrapment of the enzyme in the cellulose matrix promoted the stability of the enzyme, as revealed by data on the enzyme activity after the enzyme electrode was immersed in urea. Therefore, the cellulose matrix may be used to improve the performance of biosensors, bioreactors and bio-fuel cells.

Constitutive expression of cytochrome p450 genes in newly established rat hepatic cell lines.

Two cultured cell lines, called Kan-R1 and Kan-R2, were established from rat hepatic cells by in vitro culture with a hepatocarcinogen, 3-methoxy-4-aminoazobenzene, and examined for the gene expression of cytochrome p450 (p450) isoforms, CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP3A1 and CYP3A2, by the RT-PCR method. It was revealed that all the p450 genes examined were expressed in both cell lines, although the two cell lines differed in cell size and colony-forming ability on a soft agar. The expression levels of the CYP1A2, CYP2B1, CYP2B2, CYP3A1, and CYP3A2 genes were lower than those in liver tissues, while that of CYP1A1 was higher in the cell lines. In both cell lines, cycloheximide, an inhibitor of protein synthesis, augmented the gene expression of the p450s except CYP2B1. These findings indicate that the newly established hepatic cell lines substantially express the p450 genes for CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP3A1, and CYP3A2, and that the constitutive gene expression of these p450s, with the exception of CYP2B1, may be inhibited by negative transcription factors.