Brief communication: developmental dysplasia of the hip in medieval London

Developmental dysplasia of the hip (DDH) is a spectrum of disease starting in childhood and in many cases persisting into adulthood. The spectrum ranges from acetabular dysplasia, through hip subluxation to dislocation. The aim of this research was to determine the prevalence and pathoanatomy of acetabular dysplasia and subluxation in excavated human skeletal remains, to complement past research on dislocation in DDH. The material under study was the medieval cemetery of St. Mary Spital in London, in use from c.1100 to 1539 AD. A series of 572 adults with both hips preserved were analyzed. Acetabular dysplasia was indicated by a shallow acetabulum with upward sloping roof. Subluxation was suggested by degenerative change along the margin of the acetabulum suggestive of labral tears, and degenerative change in the outer part of the acetabular roof suggestive of osteoarthritis. The prevalence of DDH (acetabular dysplasia, subluxation, or dislocation) was 1.7%. Because this a congenital musculoskeletal disorder of relatively high frequency, with significant variation in prevalence between populations around the world, it is a topic that warrants targeted research from physical anthropologists studying past populations.     

Investigation of explanted hip and acetabulum hip prostheses]

Retrieved ceramic femoral heads and acetabular cups were investigated. On the basis of the case studies, the reasons for revision are discussed. Wear patterns and wear rates were found to differ from those observed in hip simulating testing. Monolithic ceramic cups showed a high wear rate. Owing to their limited range of motion, ceramic "mushroom heads" are associated with impingement that leads to a high risk of cup loosening, high wear rates and in vivo fractures. The combination of ceramic "mushroom heads" and cups is not recommended. An evaluation of complications shows that some can be explained by patient behaviour--e.g. Japanese sitting position, horse riding. Designers need to develop new concepts offering a larger range of motion, for example, with head diameters of 32 and 36 mm that reduce the risk of impingement, subluxation and dislocation, while increasing the range of motion. The potential of ceramic/ceramic coupling has been known since the 70s, and ceramic concepts for total hip replacement are currently experiencing a renaissance, although further developments are still possible.     

Ultrasonography in screening for developmental dysplasia of the hip in newborns: systematic review

Objective To assess the accuracy and effectiveness of the screening of all newborn infants for developmental dysplasia of the hip (DDH) using ultrasound imaging, as is standard practice in some European countries but not in the United Kingdom, the United States, or Scandinavia.Design Systematic review.Data sources Twenty three medical, economic, and grey literature databases (to March 2004), with no limitations of design or language; some references were provided by experts.Selection of studies Only diagnostic accuracy studies and comparative studies conducted in an unselected newborn population were eligible for the review. Two reviewers independently selected the studies and performed the quality assessment.Results The review identified one diagnostic accuracy study, and this was of limited quality. In this study the reference standard was treatment up to age of 8 months or an abnormal ultrasound finding at age 8 months. Ultrasound screening had a sensitivity of 88.5% (95% confidence interval 84.1% to 92.1%), specificity of 96.7% (96.4% to 97.4%), a positive predictive value of 61.6% and a negative predictive value of 99.4%. Ten studies evaluated the impact of ultrasound in screening, but these too had various methodological weaknesses, limiting the reliability of their findings. Compared with clinical screening, general ultrasound screening in newborns may increase overall treatment rates, but ultrasound screening seems to be associated with shorter and less intrusive treatment.Conclusions Clear evidence is lacking either for or against general ultrasound screening of newborn infants for DDH. Studies that investigate the natural course of the disorder, the optimal treatment for DDH, and the best strategy for ultrasound screening are needed.     

The advancement in the early diagnostics of developmental hip dysplasia in infants--the role of ultrasound screening

Developmental hip dysplasia (DDH) is a deformation of the locomotor system that can occur on previously normal bone structures in late fetal development. The study was undertaken to determine the value of continuous ultrasound screening in early diagnosis of DDH. In the area covered by the Labin Primary Health Center, clinical and ultrasound examination of the hips was performed in all children during the fourth month of life from 1989 to 2001. The incidence of DDH was 3.3%. The authors compared the obtained results with results of clinically examined hips in the period from 1968 to 1988 (incidence 1.7%), before the ultrasound diagnostics was introduced. The hip radiograms were performed only in children with clinically positive signs of higher degree of DHD. The ultrasound examination was performed with Hitachi EUB 410 real time linear transducer with a 5 MHz probe. The examiners used methods and criteria suggested by Graf. The most useful feature of the ultrasound method is that it allows the visualization of cartilaginous femoral head and its relationship to the acetabulum in infants. The method is non-invasive, repeatable, without risk of ionizing radiation or need for the contrast material administration. The results of the study revealed an important increase of DHD incidence after the introduction of ultrasound examination. US is highly sensitive in hip imaging and reveals the existence of a number of dislocated and subluxated hips that otherwise would be missed. The anomaly was discovered in the early period of life, which is very important for appropriate therapeutic effects.     

The computer-assisted spatial reconstruction of the hip acetabulum

Computer aided design is a useful method in presenting graphics. By 2 simple computer programs written in BASIC and running on most home computers very clear plots of the 3-dimensional (3D) structure of joints like the acetabulum can be drawn quickly. By orthogonal transformations the 3D-body may be easily regarded from every possible point of view. The surface of the acetabulum may be emphasized by an optional automatic hatching between adjacent cutting bows. Further methods of automatic data entering from given joints are discussed.     

Association analysis between four vitamin D receptor gene polymorphisms and developmental dysplasia of the hip

Developmental dysplasia of the hip (DDH) is a congenital condition characterized by abnormality in acetabulum size and/or shape. The incidence rate of DDH differs between different populations with risk factors including positive family history, breech presentation, sex, firstborn status, side of the hip, mode of delivery and oligohydramnios. It is recognized that DDH has a genetic component that exhibit autosomal dominant patterns. Many candidate genes have been studied and found to be associated with the disease; most of them are normally involved in cartilage development and joint metabolism. In this study, the association of four single-nucleotide polymorphisms (SNPs) (rs731236, rs1544410, rs7975232 and rs2228570) in the vitamin D receptor (VDR) gene was studied by a case–control analysis. The study sample involves 50 cases with confirmed DDH presentation and 50 nonDDH controls. SNPs were genotyped using conventional polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) techniques. Genotype and allele frequencies were analysed using SPSS software. No significant associations were found between the VDR polymorphisms analysed and DDH. Further work need to be performed using genomewide analysis to elucidate the genetic basis of DDH.     

Knee osteoarthritis,lumbar-disc degeneration and developmental dysplasia of the hip - an emerging genetic overlap

Genetics highlights relationships between biological systems, and as the number of defined osteoarthritis susceptibility alleles increases, there is the natural tendency to assess whether the alleles influence other musculoskeletal phenotypes. That has proven to be the case for the GDF5 polymorphism rs143383, a risk factor for knee osteoarthritis and several other common conditions, including lumbar-disc degeneration and developmental dysplasia of the hip. Another interesting example has recently emerged in the repeat polymorphism of the asporin gene, ASPN, which is also associated with these three phenotypes. Such discoveries increase our understanding of shared disease etiology but also emphasize the complexity of common genetic risk.     

Whole genome sequencing of pairwise human subjects reveals DNA mutations specific to developmental dysplasia of the hip

Developmental dysplasia of the hip (DDH) is a common congenital malformation characterized by mismatch in shape between the femoral head and acetabulum, and leads to hip dysplasia. To date, the pathogenesis of DDH is poorly understood and may involve multiple factors, including genetic predisposition. However, comprehensive genetic analysis has not been applied to investigate a genetic component of DDH. In the present study, 10 pairs of healthy fathers and DDH daughters were enrolled to identify genetic hallmarks of DDH using high throughput whole genome sequencing. The DDH-specific DNA mutations were found in each patient. Overall 1344 genes contained DDH-specific mutations. Functional enrichment analysis showed that these genes played important roles in the cytoskeleton, microtubule cytoskeleton, sarcoplasm and microtubule associated complex. These functions affected osteoblast and osteoclast development. Therefore, we proposed that the DDH-specific mutations might affect bone development, and caused DDH. Our pairwise high throughput sequencing results comprehensively delineated genetic hallmarks of DDH. Further research into the biological impact of these mutations may inform the development of DDH diagnostic tools and allow neonatal gene screening.     

Hemiarthroplasty of hip joint: An experimental validation using porcine acetabulum

Biphasic properties of articular cartilage allow it to be an excellent bearing material and have been studied through several simplified experiments as well as finite element modelling. However, three-dimensional biphasic finite element (FE) models of the whole joint are rare. The current study was carried out to experimentally validate FE methodology for modelling hemiarthroplasty. Material properties such as equilibrium elastic modulus and permeability of porcine acetabular cartilage were initially derived by curve-fitting an experimental deformation curve with that obtained using FE. These properties were then used in the hemiarthroplasty hip joint modelling. Each porcine acetabular cup was loaded with 400N using a 34mm diameter CoCr femoral head. A specimen-specific FE model of each acetabular cup was created using μCT and a series of software processes. Each model was analysed under conditions similar to those tested experimentally. Contact stresses and contact areas predicted by the model, immediately after loading, were then compared with the corresponding experimentally measured values. Very high peak contact stresses (maximum experimental: 14.09MPa) were recorded. A maximum difference of 12.42% was found in peak contact stresses. The corresponding error for contact area was 20.69%. Due to a fairly good agreement in predicted and measured values of contact stresses and contact areas, the integrated methodology developed in this study can be used as a basis for future work. In addition, FE predicted total fluid load support was around 80% immediately after loading. This was lower than that observed in conforming contact problems involving biphasic cartilage and was due to a smaller local contact area and variable clearance making fluid exudation easier.     

Early x-ray diagnosis of hip dysplasia in children]

The author proposes a method of differential diagnosis of hip dislocations and hip joint dysplasia in infants aged 3 months. The alpha-angle of hip dislocation with relation to trochanteric space is determined on an anteroposterior radiogram of the hip joints; 64 degrees means hip dysplasia, 65-69 degrees and more mean dislocation. This method was tested in 75 children (150 joints) aged 3 months. A mean diagnostic accuracy was 90.1%.     

Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese

Introduction

Developmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-β1 and sequentially inhibit TGF-β/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritis-associated polymorphism. As TGF-β is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese.

Methods

The D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined.

Results

From D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined.

Conclusions

Our results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.     

Differential genetic regulation of canine hip dysplasia and osteoarthritis

Background

Canine hip dysplasia (HD) is a common polygenic trait characterized by hip malformation that results in osteoarthritis (OA). The condition in dogs is very similar to developmental dysplasia of the human hip which also leads to OA.

Methodology/Principal Findings

A total of 721 dogs, including both an association and linkage population, were genotyped. The association population included 8 pure breeds (Labrador retriever, Greyhounds, German Shepherd, Newfoundland, Golden retriever, Rottweiler, Border Collie and Bernese Mountain Dog). The linkage population included Labrador retrievers, Greyhounds, and their crosses. Of these, 366 dogs were genotyped at ∼22,000 single nucleotide polymorphism (SNP) loci and a targeted screen across 8 chromosomes with ∼3,300 SNPs was performed on 551 dogs (196 dogs were common to both sets). A mixed linear model approach was used to perform an association study on this combined association and linkage population. The study identified 4 susceptibility SNPs associated with HD and 2 SNPs associated with hip OA.

Conclusion/Significance

The identified SNPs included those near known genes (PTPRD, PARD3B, and COL15A1) reported to be associated with, or expressed in, OA in humans. This suggested that the canine model could provide a unique opportunity to identify genes underlying natural HD and hip OA, which are common and debilitating conditions in both dogs and humans.     

Complex segregation analysis of canine hip dysplasia in German shepherd dogs

Complex segregation analyses were carried out to clarify the mode of inheritance of canine hip dysplasia (CHD) in German shepherd dogs. Data were used from 8,567 animals examined for CHD from 20 families with three to four generations. The existence of a major gene in addition to polygenic gene effects was detected. In the present study, a mixed model with a dominant major gene effect seemed to be most probable for dichotomous encoding (0: dogs without signs of CHD; 1: dogs with borderline/slight to severe CHD). In addition, mixed major gene inheritance was shown for a binary trait where borderline was assigned to dogs scored free from CHD and for a trichotomously encoded trait (0: dogs without signs of CHD; 1: borderline CHD; 2: mild to severe CHD). Although only small frequencies were found for the unfavorable homozygotic genotype AA, the probability of the AB genotype was high in affected animals. Selection schemes to reduce the frequency of the allele A should therefore efficiently improve existing breeding programmes in German shepherd dogs.     

Secondary hip dysplasia increases risk for early coxarthritis after Legg-Calve-Perthes disease. A study of 255 hips

Abstract

The biomechanical parameters of the hip joint articular surface were analysed in 141 adult hips after Legg-Calve Perthes Disease, and 114 contralateral unaffected hips (controls), by using HIPSTRESS mathematical models. Geometrical parameters, assessed from anteroposterior and axial radiograms, were used as input to models for resultant hip force and contact hip stress. Results confirm previous indications that head enlargement after the Legg-Calve-Perthes Disease compensates the values of hip stress. Furthermore, it was found that an increased risk for coxarthritis development after the disease is secondary to concomitant hip dysplasia, with considerable and statistically significantly lower centre-edge angle and unfavourable distribution of stress.     

Simulator for migration processes and wear in the artificial hip acetabulum for radiologic measurement]

For assessing migration of cups, standard X-rays or stereo radiological images (SRI) are available. In addition, software is also available for measurements. The accuracies of the various systems are established statistically, in part combined with phantoms, and compared. To date, no known phantom is available for the simulation of acetabular cup migration with account being taken of the position of the pelvis in the X-ray beam. Such an appliance covering 8 different parameters has now been developed, the cup can be moved horizontally, vertically and in the loading direction. Angular accuracy is +/- 0.5 degree, and wear of a magnitude of 0.25 mm can be simulated. Two degree elevation of the pelvis, left or right, can be simulated. The position of the pelvis around the horizontal axis permits continuous variation. This appliance can simulate migratory movements of the acetabular cup within a pelvis, and wear within the cup. In addition, the spatial position of the pelvis can be varied. The X-ray images can be used to investigate the accuracy of evaluation strategies.     

Increasing expression of substance P and calcitonin gene-related peptide in synovial tissue and fluid contribute to the progress of arthritis in developmental dysplasia of the hip

IntroductionDevelopmental dysplasia of the hip (DDH) is a common musculoskeletal disorder that has pain and loss of joint function as major pathological features. In the present study, we explored the mechanisms of possible involvement and regulation of substance P (SP) and calcitonin gene-related peptide (CGRP) in the pathological and inflammatory processes of arthritis in DDH.MethodsBlood, synovial tissue and fluid samples were collected from patients diagnosed with different severities of DDH and from patients with femoral neck fracture. Levels of SP, CGRP and inflammatory cytokines in synovium and synovial fluid (SF) in the different groups were evaluated by immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assay (ELISA). Correlations between neuropeptides and inflammatory cytokines in SF were evaluated by partial correlation analysis. The proinflammatory effects of SP and CGRP on synoviocytes obtained from patients with moderate DDH were investigated in vitro by real-time PCR and ELISA. The mechanisms of those effects were evaluated by Western blot analysis and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) DNA binding assay.ResultsSignificantly increased levels of neuropeptides and inflammatory cytokines were observed in synovium and SF from patients in the severe DDH group compared with the moderate DDH and control groups. In moderate DDH samples, SP in SF correlated with tumor necrosis factor (TNF)-α, and CGRP in SF correlated with TNF-α and interleukin (IL)-10. In the severe DDH group, SP in SF correlated with interleukin (IL)-1β, TNF-α and IL-10. CGRP in SF correlated with TNF-α. Additionally, SP might have had obvious proinflammatory effects on synoviocytes through the activation of NF-κB.ConclusionsThe upregulation of SP and CGRP in synovium and SF might participate in the inflammatory process of arthritis in DDH. The activation of the NF-κB pathway seems indispensable in the proinflammatory effect of SP on synoviocytes. This original discovery may indicate a potential clinical drug target and the development of innovative therapies for DDH.