Does cranial bone ossification differ in children with developmental dysplasia of the hip?

OBJECTIVES: This study aims to compare cranial bone ossification between patients with developmental dysplasia of the hip (DDH) and healthy individuals. PATIENTS AND METHODS: Between September 2021 and April 2022, a total of 60 healthy female individuals (median age: 24.5 months; range, 18 to 36 months) and 56 female DDH patients (median age: 23 months; range, 18 to 35 months) were included. Age, head circumference, weight, height, and patency of the anterior fontanel were measured in groups. Percentiles were classified as very low, low, normal, high and very high. All patients were female and those with abnormal thyroid function test, vitamin D, calcium, phosphate and alkaline phosphatase values were not included in the study. For those diagnosed with DDH, they were included in the group regardless of the type of treatment. RESULTS: No statistically significant difference was found between the groups in terms of age and weight (p>0.05). The very low and very high head circumferences were more frequent, and the normal head circumferences were less frequent in the DDH group (p<0.05). There was no significant difference between groups in terms of fontanel closure (p>0.05). In open fontanels, no significant difference was found in both groups in terms of age (p>0.05). CONCLUSION: Our study results showed no significant difference between the fontanel ossifications of children with and without DDH; however, we found that the ossification of the skull bones of children with DDH was different compared to healthy children.

AP Radiographic Assessment of the Pediatric Pelvis for Developmental Dysplasia of the Hip.

Mastering the art of roentgenographic analysis of the pediatric AP pelvis is paramount in the evaluation of developmental dysplasia of the hip. Understanding the normal radiographic development and the age-dependent changes in normal values allows assessment for pathologic changes. The goal of improving the analysis of the AP pelvis is to increase early detection of disease, assess progress toward normal values, and precisely follow the effects of treatment to improve clinical outcomes.

Heterozygous LRP1 deficiency causes developmental dysplasia of the hip by impairing triradiate chondrocytes differentiation due to inhibition of autophagy.

Developmental dysplasia of the hip (DDH) is one of the most common congenital skeletal malformations; however, its etiology remains unclear. Here, we conducted whole-exome sequencing in eight DDH families followed by targeted sequencing of 68 sporadic DDH patients. We identified likely pathogenic variants in the LRP1 (low-density lipoprotein receptor-related protein 1) gene in two families and seven unrelated patients. All patients harboring the LRP1 variants presented a typical DDH phenotype. The heterozygous Lrp1 knockout (KO) mouse (Lrp1+/-) showed phenotypes recapitulating the human DDH phenotypes, indicating Lrp1 loss of function causes DDH. Lrp1 knockin mice with a missense variant corresponding to a human variant identified in DDH (Lrp1R1783W) also presented DDH phenotypes, which were milder in heterozygotes and severer in homozygotes than those of the Lrp1 KO mouse. The timing of triradiate cartilage development was brought forward 1 or 2 wk earlier in the LRP-deficient mice, which leads to malformation of the acetabulum and femoral head. Furthermore, Lrp1 deficiency caused a significant decrease of chondrogenic ability in vitro. During the chondrogenic induction of mice bone marrow stem cells and ATDC5 (an inducible chondrogenic cell line), Lrp1 deficiency caused decreased autophagy levels with significant ß-catenin up-regulation and suppression of chondrocyte marker genes. The expression of chondrocyte markers was rescued by PNU-74654 (a ß-catenin antagonist) in an shRNA-Lrp1-expressed ATDC5 cell. Our study reveals a critical role of LRP1 in the etiology and pathogenesis of DDH, opening an avenue for its treatment.

Accuracy of CT for measuring femoral neck anteversion in children with developmental dislocation of the hip verified using 3D printing technology.

BACKGROUND: Accurate femoral neck anteversion angle (FNA) measurement is of great significance in the diagnosis and treatment of developmental dysplasia of the hip (DDH) in children. The FNA measurement still remains a controversy. We aimed to verify the accuracy of our CT method by 3D printing technology and to evaluate its clinical value. METHODS: Sixty-eight children with unilateral DDH were enrolled, and their FNA was measured using 2D-CT and 3D-CT, respectively, by three observers. This procedure was repeated 3 months later. The above measurement outcomes were then compared with the results in the 3D-printed femur (3D-PF) model. The FNA in the 3D-PF model was measured by three observers (two radiologists and one orthopedist; all were professors) collectively through electronic angle instrument. RESULTS: The primary measurement of FNA at the affected hips by 2D-CT was 44.0 ± 6.1, 49.5 ± 8.9, and 52.8 ± 7.9°, respectively. On the 3D-CT, it was 47.6 ± 5.4, 49.3 ± 6.8, and 48.6 ± 6.2°. Three months later, the FNA on 2D-CT was 49.3 ± 10.5, 42.8 ± 7.4, and 45.1 ± 9.3°, and it was 48.0 ± 6.5, 48.9 ± 7.2, and 49.0 ± 5.7° on 3D-CT, respectively. The FNA in the 3D-PF model at the affected and unaffected hips was 48.5 ± 6.6 and 36.9 ± 13.1°. There were significant differences between 2D-CT and 3D-PF measurements, but no significant difference was found between 3D-CT and 3D-PF measurements. The results by 2D-CT showed significant differences among groups and between the groups. However, the results by 3D-CT had no significant differences among groups or between the groups. CONCLUSION: The results of our study showed that 3D-CT is a more precise, and reproducible method for FNA measurement in DDH. The FNA at the affected hips is 11.6° larger than the unaffected in DDH children aged 3-8 years.

Clinical evaluation of direct anterior approach total hip arthroplasty for severe developmental dysplasia of the hip.

It is challenging to treat developmental dysplasia of the hip (DDH) classified Crowe III-IV using direct anterior approach (DAA) total hip arthroplasty (THA), and very little is known on its outcome. This study aimed to investigate the clinical result in this defined disorder with DAA versus posterolateral approach. Twenty-three consecutive hips with Crowe III-IV DDH who underwent DAA were retrospectively evaluated from 2016 through 2018. Outcomes were primarily assessed by HHS, WOMAC, and SF-12 physical scales. The second evaluations included leg length discrepancy, hip muscle strength, radiographic review, complications, and limp recovery. Results were compared to a control cohort of 50 hips underwent posterolateral THA concurrently within the observational period. At last follow-up (DAA 28.5 months; PLA 39.0 months), the mean increase of the HHS for DAA was 48.2 and 30.3 for PLA (p = 0.003). The improvement in WOMAC score in DAA cohort was 15.89 higher that of the PLA cohort after adjusting preoperative difference [R2 = 0.532, P = 0.000, 95% CI (10.037, 21.735)]. DAA had more rapid recovery of hip abductor strength at 1-month (p = 0.03) and hip flexor strength at 3 months (p = 0.007) compared to PLA. No significant differences were found in the radiographic analysis with the exception of increased acetabular anteversion in the DAA cohort (p = 0.036). Satisfactory improvement in limp, indicated by the percentage of limp graded as none and mild to the total, was much higher in DAA cohort (97.6%), compared to that of PLA cohort (90.0%, p = 0.032). DAA for high-dislocated dysplasia demonstrate a significant improvement in clinical result comparable to posterolateral approach. Improved clinical outcome in terms of increased HHS and WOMAC scores, rapid recovery of hip abductor and flexor strength, and enhanced limp recovery without an increased risk in complications, could be acquired when the surgeons were specialized in this approach.

Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. METHODS: Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of FRZB was performed. FRZB expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of FRZB were conducted. Potential upstream miRNAs for FRZB were assayed in DDH. RESULTS: Significant difference in genotype distribution for rs3768842 (OR=1.46, P=0.0081) and rs2242040 (OR=0.65, P=0.0067) was found. DDH joint tissues showed significantly higher FRZB expression. FRZB demonstrated chondrogenic and anti-hypertrophic properties in vitro. FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. Upstream miRNAs regulating FRZB expression were identified in DDH synovial fluid. Experiments indicated that downregulated miRNA-454 caused FRZB upregulation in DDH joint. CONCLUSION: Dysregulated FRZB and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. FRZB in multiple DDH joint tissues might be mediated by the dysregulated miRNA expression profiles in the joint synovial fluid.

Correlation of the anatomical sacral slope with pelvic incidence in female patients with developmental hip dysplasia: a retrospective cross-sectional study.

BACKGROUND: The anatomical sacral slope is considered as an anatomical pelvic parameter independent of femoral head centers for measurement of anatomical sacral slope and was previously described to strongly correlate with pelvic incidence on a two-dimensional examination of healthy subjects. However, the correlation between anatomical sacral slope and pelvic incidence was unclear in patients with developmental dysplasia of the hip. This study aimed to examine the correlation between anatomical sacral slope and other spinopelvic parameters by analyzing plain radiographs of female patients with developmental dysplasia of the hip. METHODS: Eighty-four women with developmental dysplasia of the hip were examined. Lumbar lordosis, thoracic kyphosis, pelvic incidence, sacral slope, and anatomical sacral slope (the angle formed by the straight line of the S1 superior endplate and a line at a right angle to the anterior pelvic plane) were determined by analyzing plain radiographs. The correlations were examined by Pearson's correlation coefficients, and intra- and inter-rater intraclass correlation coefficients were evaluated for reliability. RESULTS: A strong correlation was observed between pelvic incidence and anatomical sacral slope (r = 0.725, p < 0.001). In addition, the correlation between anatomical sacral slope and lumbar lordosis was similar to that between pelvic incidence and lumbar lordosis (r = 0.661, p < 0.001, and r = 0.554, p < 0.001, respectively). The intra-rater intraclass correlation coefficient values were 0.869 and 0.824 for anatomical sacral slope and pelvic incidence, respectively. Furthermore, the inter-rater intraclass correlation coefficient values were 0.83 and 0.685 for anatomical sacral slope and pelvic incidence, respectively. CONCLUSIONS: We observed that the strong correlation between anatomical sacral slope and pelvic incidence in patients with developmental dysplasia of the hip was equal to that in normal healthy subjects. The correlation between anatomical sacral slope and lumbar lordosis was equal to that between pelvic incidence and lumbar lordosis. Additionally, the intraclass correlation coefficient values for the anatomical sacral slope were slightly higher than those for pelvic incidence. Thus, we conclude that anatomical sacral slope can be considered as a helpful anatomical pelvic parameter that is a substitute for pelvic incidence not only in normal healthy subjects, but also in patients with developmental dysplasia of the hip.

The long noncoding RNA H19 attenuates force-driven cartilage degeneration via miR-483-5p/Dusp5.

Developmental dysplasia of the hip (DDH) is a common hip disease characterized by abnormal development of the acetabulum and femoral head. In most cases, DDH ultimately leads to osteoarthritis. Anomalous biomechanical force plays an important role in cartilage degeneration in DDH. However, in addition to mechanical wear, the underlying molecular mechanisms in cartilage degeneration in DDH remain unclear. This study analyzed the effect of long noncoding RNA (lncRNA)-H19 on DDH cartilage degradation. To elucidate the specific role of lncRNA H19, we established an intermittent cyclic mechanical stress (ICMS) cell force model to simulate abnormal biomechanical environment in vitro. Then, the roles of lncRNA-H19 were also determined in vivo by establishing a model of swaddling DDH. We observed that patients with DDH possessed low levels of lncRNA-H19, COL2A1, and Aggrecan but high levels of MMP3 and Adamts5. The same results were also obtained in a DDH rat model. Furthermore, the data suggested that ICMS promoted cartilage degeneration and caused reorientation of the cytoskeleton, and lncRNA H19 helped inhibit cartilage degeneration. Bioinformatics analysis and lncRNA sequencing were performed, and luciferase assays showed that lncRNA H19 and Dusp5 are both direct targets of miR-483-5p. Moreover, Dups5 plays a negative role in ICMS-induced cartilage degradation by activating the Erk and p38 pathways. In vivo, lncRNA H19 had protective effects on the swaddling DDH model. These findings indicate that lncRNA-H19 played a positive role in cartilage degradation in DDH through the lncRNA H19/miR-483-5p/Dusp5 axis.

Genetics of developmental dysplasia of the hip.

In the last decade, the advances in the molecular analyses and sequencing techniques allowed researchers to study developmental dysplasia of the hip (DDH) more thoroughly. Certain chromosomes, genes, loci and polymorphisms are being associated with variable severity of this disorder. The wide range of signs and symptoms is dependent either on isolated or systemic manifestation. Phenotypes of isolated cases range from only a mild ligamental laxity, through subluxation, to a complete dislocation of the femoral head. Systemic manifestation is connected to various forms of skeletal dysplasia and other malformations characterized by significant genetic aberrations. To reveal the background of DDH heredity, multiple studies focused on large sample sizes with an emphasis on the correlation between genotype, phenotype and continuous clinical examination. Etiological risk factors that have been observed and documented in patients include genetic, environmental, and mechanical factors, which significantly contribute to the familial or nonfamilial occurrence and phenotypic variability of this disorder. Still, the multifactorial etiology and pathogenesis of DDH are not yet sufficiently clarified, explained, or understood. Formation of connective tissue, osteogenesis, chondrogenesis, and all other affected pathways and variations in the function of their individual elements contribute to the creation of the pathology in a developing human body. This review article presents an up-to-date list of known DDH associated genes, their products, and functional characteristics.

Biomechanical investigation of pelvic stability in developmental dysplasia of the hip: unilateral salter osteotomy versus one-stage bilateral salter osteotomy.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common disease in infants and children, and the treatment of bilateral DDH remains controversial. This study aimed to evaluate the stability of one-stage bilateral Salter pelvic osteotomy for bilateral DDH in patients of walking age. METHODS: In total, nine child cadavers aged 2-6 years were included. A universal mechanical testing machine was used for stability test. We performed two different surgical procedures on the specimens: nine child cadavers underwent unilateral Salter pelvic osteotomy, and six child cadavers were randomly selected to undergo Salter pelvic osteotomy again to simulate one-stage bilateral Salter pelvic osteotomy. The stability of the bilateral sacroiliac joints, local stability of the operation area, ultimate load test, and axial stiffness were evaluated. RESULTS: Both unilateral and bilateral Salter osteotomy could destroy the integrity of the pelvic ring and increase the risk of pelvic instability. In this study, compared with unilateral Salter osteotomy, bilateral Salter osteotomy had similar pelvic stability, and there was no significant difference between unilateral and bilateral Salter osteotomy in sacroiliac joint stability (p > 0.05), local stability (p = 0.763), ultimate load (p = 0.328), and axial stiffness (p = 0.480). CONCLUSIONS: One-stage bilateral Salter pelvic osteotomy as a potential surgical method is viable and stable for children with bilateral DDH.