Developmental Dysplasia of the Hip

ImportanceUniversal ultrasonographic screening for developmental dysplasia of the hip (DDH) has gained increasing popularity despite the lack of benefit in terms of reducing the rates of late-detected cases (age ≥12 weeks) in randomized clinical trials.ObjectiveTo report the reported incidence of DDH in the English scientific literature and compare rates of late-detected cases in settings with different DDH screening strategies.Data sourcesPubMed, Scopus, and Web of Science databases were searched on November 25 and 27, 2021. No time filters were used in the search.Study selectionAll observational studies reporting the incidence of early-detected or late-detected (age ≥12 weeks) DDH were included. Non-English reports were excluded if the abstract did not include enough information to be included for analysis.Data extraction and synthesisThe number of newborns screened and the detection rates were extracted. Meta-analysis calculated the pooled incidence of DDH per 1000 newborns with 95% CIs using a random- or fixed-effects model. This study is reported according to the PRISMA and MOOSE guidelines.Main outcomes and measuresThe main outcome measures were early detection, early treatment, late detection, and operative treatment incidences.ResultsA total of 1899 studies were identified, 203 full texts were assessed, and 76 studies with 16 901 079 infants were included in final analyses. The early detection rate was 8.4 (95% CI, 4.8-14.8) infants with DDH per 1000 newborns with clinical screening, 4.4 (95% CI, 2.4-8.0) infants with DDH per 1000 newborns with selective ultrasonographic screening, and 23.0 (95% CI, 15.7-33.4) infants with DDH per 1000 newborns with universal ultrasonographic screening. Rates for nonoperative treatment were 5.5 (95% CI, 2.1-14) treatments per 1000 newborns with clinical screening, 3.1 (95% CI, 2.0-4.8) treatments per 1000 newborns with selective ultrasonographic screening, and 9.8 (95% CI, 6.7-14.4) treatments per 1000 newborns with universal ultrasonographic screening. The incidence of late-detected DDH was 0.5 (95% CI, 0.2-1.5) infants with DDH per 1000 newborns with clinical screening, 0.6 (95% CI, 0.3-1.3) infants with DDH per 1000 newborns with selective ultrasonographic screening, and 0.2 (95% CI, 0.0-0.8) infants with DDH per 1000 newborns with universal ultrasonographic screening. The corresponding incidences of operative treatment were 0.2 (95% CI, 0.0-0.9) operations per 1000 newborns with clinical screening, 0.5 (95% CI, 0.4-0.7) operations per 1000 newborns with selective ultrasonographic screening, and 0.4 (95% CI, 0.2-0.7) operations per 1000 newborns with universal ultrasonographic screening.Conclusions and relevanceThis meta-analysis found that early detection rates and nonoperative treatments were higher with universal screening. The late detection and operative treatment rates with universal screening were similar to those among selectively and clinically screened newborns. Based on these results, universal screening may cause initial overtreatment without reducing the rates of late detection and operative treatment.

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 β-catenin up-regulation and suppression of chondrocyte marker genes. The expression of chondrocyte markers was rescued by PNU-74654 (a β-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.

PurposeThis systematic review and meta-analysis aimed to compare the outcomes of total hip arthroplasty (THA) in patients with developmental dysplasia of the hip (DDH) and those with osteoarthritis (OA).MethodsFour databases were searched from inception till February 2023 for original studies that compared the outcomes of THA in DDH and OA. The primary outcome was the revision rate; the secondary outcomes were dislocation and failure modes (i.e. aseptic loosening, PJI, instability, and periprosthetic fractures), hospital stay and costs. This review was conducted as per PRISMA guidelines, and the risk of bias was assessed using the Newcastle-Ottawa scale.ResultsA total of 9 observational studies with 575,255 THA (469,224 hips) were included, with a mean age of 50.6 years and 62.1 years for DDH and OA groups, respectively. There was a statistically significant difference in revision rate between DDH and OA patients in favour of OA (OR, 1.66; 95% CI 1.11-2.48; p-value, 0.0251). However, dislocation rate (OR, 1.78, 95% CI 0.58-5.51; p-value, 0.200), aseptic loosening (OR, 1.69; 95% CI 0.26-10.84; p-value, 0.346) and PJI (OR, 0.76; 95% CI 0.56-1.03; p-value, 0.063) were comparable across both groups.ConclusionA higher revision rate following total hip arthroplasty was associated with DDH compared with osteoarthritis. However, both groups had similar dislocation rates, aseptic loosening and PJI. Consideration of confounding factors, such as patient age and activity level, is crucial when interpreting these findings. LEVEL OF EVIDENCE : III.Trial registrationPROSPERO registration: CRD42023396192.

Developmental dysplasia of the hip (DDH), a morphological abnormality of the hip joint, is a well-recognized risk factor for hip osteoarthritis (OA). Much remains unknown about the genetic factors of DDH and its subtypes. To further understand its genetic basis, we conducted genome-wide association studies (GWASs) using a total of 1 085 Japanese DDH cases (including 788 hip dysplasia cases without dislocation and 297 cases with dislocated hip) and 24 000 controls. Additionally, we meta-analyzed with United Kingdom (UK) DDH GWAS and the largest hip OA GWAS to date. We identified three genome-wide significant novel loci, COL11A2, CALN1 and TRPM7, associated with hip dysplasia without dislocation. None of these signals were significant in dislocated hips, and additionally two of the signals had an opposite direction of association, suggesting distinct genetic architectures between the subtypes. The Japanese DDH GWAS identified five associated loci (VEGF-C, FOXC1, SMC2, SLC38A4, and TRPM7), and the trans-ancestry meta-analysis with UK revealed two loci (COL11A1 and GDF5) supported by strong trans-ancestry genetic correlation (r = 1.0). In total, nine loci were identified for DDH and its subtypes, with hip dysplasia without dislocation showing distinct genetic signals from hip dislocation. The meta-analysis of DDH and hip OA identified five novel signals for hip OA. Susceptibility loci and heritability enrichment analyses implicated pathways involving bone formation, collagen type XI trimer, and chondrocyte development, as well as their gene regulation, in DDH. These findings enhance understanding of the genetic architecture and biological pathways underlying DDH, providing new insights into its relationship with OA.