Development Of Developmental Dysplasia Of The Hip Research Articles

Ultrasonography in the evaluation of various factors of developmental dysplasia of the hip in infants: Results from a retrospective study in a large hospital of northwest China

BackgroundThe occurrence and development of developmental dysplasia of the hip (DDH) are related to a variety of factors, which have been reported in the literature, but the literature does not mention factors related to the severity of DDH. The purpose of this study is to analyze the related factors of the occurrence and severity of DDH in combination with the Graf ultrasonic diagnostic classification. MethodsThis study was a monocentric retrospective study describing the factors associated with DDH in a large hospital of northwest China. A total of 3046 infants (6092 hips) within 6 months after birth using the Graf method were admitted to our department between 2014 and 2018. We analyzed data of DDH. After reviewing medical charts and diagnostic examination results, we assessed whether factors such as ethnicity, gender, gestational age, birth weight, diagnosis age, maternal age, mode of delivery, fetal presentation, amniotic fluid volume and birth order, had any effect on development of hip. Result① Analysis showed that DDH mostly occurs in female and left hip joint, related to intrauterine fetal presentation, amniotic fluid volume, gestational age, mode of delivery, prenatal weight, and diagnosis age after birth, and the occurrence of DDH is also related to maternal age (All P＜0.05). Ethnicity and first born showed have no obvious correlation with DDH incidence (p = 0.718, 0.147, respectively). ② The strongest correlation was found with amniotic fluid, followed by birth weight. ③ The severity of DDH was correlated with ethnicity, births, prenatal weight, gestational age, diagnosis age and maternal age (All P＜0.05, respectively). ④ There were significant differences in treatment methods, duration and prognosis among different types of DDH. ConclusionsThe occurrence and development of DDH are related to a variety of factors. Ultrasound examination can provide an early assessment of the hip development status of infants and may play an important role in establishing an early clinical diagnosis treatment and monitoring and prognosis.

Developmental dysplasia of the hip is common in patients undergoing total hip arthroplasty under 50years of age.

Developmental dysplasia of the hip (DDH) refers to congenital and/or developmental hip instability that can result in hip joint subluxation or dislocation. When detected neonatally, conservative treatment with hip bracing can restore normal hip anatomy. Missed detection of DDH in the neonatal period or late development of DDH often requires surgical intervention to correct the abnormal anatomy. Furthermore, despite surgical intervention, residual sequelae may persist leading to early osteoarthritis of the hip joint requiring joint replacement surgery. This study investigates the prevalence of hip dysplasia in patients undergoing total hip arthroplasty (THA) under 50years of age. The hip arthroplasty database at a national referral centre was investigated from January 2014 to December 2020. In patients under 50years of age, those with an adequate pre-operative anteroposterior pelvic radiograph without previous hip arthroplasty were included, while those with inadequate radiographs were excluded. The following measurements were made on the contralateral non-operated hip: (1) lateral centre-edge angle (LCEA), (2) Tönnis angle, (3) acetabular version, (4) acetabular depth, (5) femoral head lateralisation, (6) femoral head extrusion index, and (7) acetabular depth-to-width ratio. In total, 451 patients were included in this study. Twenty two percent of the patients had hip dysplasia, based on a LCEA of<25° and 42.6% of patients had hip dysplasia, based on a Tönnis angle of>10°. The mean LCEA and Tönnis angle were 31.47±9.64 and 9.82±6.79°, respectively. Hip dysplasia is common in patients undergoing THA under the age of 50years with over 40% having dysplasia according to the Tönnis angle. Classification of primary and secondary osteoarthritis in the joint registries will benefit our knowledge on the prevalence of DDH in the adult population.

Early Emergent and Progressive Aberrant Subchondral Bone Remodeling Coupled with Aggravated Cartilage Degeneration in Developmental Dysplasia of the Hip.

ObjectiveDevelopmental dysplasia of the hip (DDH) is the most common skeletal development in children and could result in secondary osteoarthritis. This study aims to clarify the alternations of subchondral trabecular bone remodeling and microstructural properties during the development of DDH, and the potential influence of these alternations on the overlying cartilage degeneration and DDH progression.DesignTraditional straight-leg swaddling method was adopted to establish DDH model in newborn Sprague Dawley rats. Hip joint specimens from normal or DDH rats were used. Typical features of DDH in radiological examination were observed by x-ray analysis. Micro–computed tomography analysis was applied to evaluate the microstructural properties of subchondral bone at postnatal weeks 2, 4, and 6. Histological and immunohistochemical analyses were adopted to appraise subchondral bone remodeling activity and cartilage degeneration. The associations among subchondral bone, articular cartilage, and DDH severity were analyzed via multiple linear regression analysis.ResultsCompared with control group, the subchondral bone in DDH group displayed a gradual trend of deteriorated microstructure and worsening biomechanical properties along with aberrant bone remodeling, which might be responsible for the inhibition of stress transmission from the articular cartilage to the subchondral bone and thus leading to the cartilage degeneration and accelerated DDH progression.ConclusionsOur findings indicate that alternations of subchondral trabecular bone in a time-dependent manner could contribute to the DDH progression and the amelioration on subchondral bone might be a favorable therapeutic candidate for DDH.

WISP-2, an upregulated gene in hip cartilage from the DDH model rats, induces chondrocyte apoptosis through PPARγ in vitro.

Chondrocyte apoptosis plays an important role in the developmental dysplasia of the hip (DDH) development. It has been found that WNT1 inducible signaling pathway protein 2 (WISP-2) and peroxisome proliferator-activated receptor γ (PPARγ) are involved in cell apoptosis. In this study, we performed the straight-leg swaddling DDH rat model and we found that cartilage degradation and chondrocyte apoptosis were remarkably increased in DDH rats in vivo. Moreover, we found that WISP-2 was upregulated in hip acetabular cartilage of DDH rats compared to control rats. Next, the effects of WISP-2 on chondrocyte apoptosis and its possible underlying mechanism were examined in vitro. The lentivirus-mediated gain- and loss-of-function experiments of WISP-2 and peroxisome proliferator-activated receptor γ (PPARγ) for cell viability and apoptosis were performed in primary rat chondrocytes. The results showed that the overexpression of WISP-2 induced chondrocyte apoptosis, and knockdown of WISP-2 could suppress the chondrocyte apoptosis induced by advanced glycation end products (AGE). Additionally, WISP-2 could negatively regulate the expression of PPARγ in chondrocytes. Moreover, the knockdown of PPARγ promoted chondrocyte apoptosis and overexpression of PPARγ abated the increased apoptosis and decreased cell viability of chondrocytes induced by WISP-2. This study demonstrated that WISP-2 might contribute to chondrocyte apoptosis of hip acetabular cartilage through regulating PPARγ expression and activation, which may play an important role in the development of DDH.

Developmental dysplasia of the hip: a systematic literature review of the genes related with its occurrence.

Developmental dysplasia of the hip (DDH) is one of the most prevalent congenital malformations. It has a wide spectrum of anatomical abnormalities of the hip joint and is characterized by mild or incomplete formation of the acetabulum leading to laxity of the joint capsule, secondary deformity of the proximal femur and irreducible hip dislocation. It is the leading cause of early hip osteoarthritis in young individuals.Both genetic and environmental factors have been proposed to play an important role in the pathogenesis of DDH. A high prevalence is present in Asian, Caucasian, Mediterranean and American populations, with females being more frequently affected. We evaluated a variety of genetic studies indexed in the PubMed database.Several susceptive genes, including WISP3, PAPPA2, HOXB9, HOXD9, GDF5, TGF Beta 1, CX3CR1, UQCC, COL1A1, TbX4 and ASPN have been identified as being associated with the development of DDH. Moreover, genetic association has also been reported between hip dysplasia and other comorbidities. Even though genetic components are a crucial part in the aetiology of DDH, several DDH susceptibility genes need further investigation.The purpose of this review is to present current literature evidence regarding genes responsible for DDH development.Cite this article: EFORT Open Rev 2019;4:595-601. DOI: 10.1302/2058-5241.4.190006

Associations between risk factors and developmental dysplasia of the hip and ultrasonographic hip type: a retrospective case control study.

PurposeWe aimed to revisit the correlation between the previously defined risk factors and the occurrence of developmental dysplasia of the hip (DDH) and to assess the influence of these factors on the ultrasonographic type of hip dysplasia according to the Graf’s classification in patients with DDH.MethodsData of healthy infants (mean age 33 days) who had bilateral mature (normal) hips (Graf type I) were compared with the data of infants (mean age 105 days) who were treated by abduction brace due to unilateral or bilateral DDH (Graf type IIa- and worse hips).ResultsInfants with at least one risk factor had a significantly higher rate of DDH than those with no risk factors (p < 0.001). Likewise, infants with more than one risk factor had a significantly higher rate of DDH than those with only one risk factor (p = 0.008). Family history, breech presentation and swaddling were found to be the three significant risk factors related to the development of DDH. Family history, swaddling and oligohydramnios were found to be the three significant risk factors correlated with a higher rate of unstable/decentred hip(s) (Graf types D/III/IV) in patients with DDH.ConclusionThe risk of DDH significantly increases in infants who have more than one risk factor for DDH. Positive family history and postnatal traditional swaddling are the two main factors both in the aetiology of DDH and in development of a more severe hip dysplasia in patients with DDH. Besides, breech presentation increases the risk of development of DDH and oligohydramnios leads to development of a more severe hip dysplasia in patients with DDH. By introducing these four variables as ‘absolute risk factors for DDH’ to the selective newborn hip screening programmes, the sensitivity and specificity of these programmes may be optimized and the risk of delayed diagnosis may be lessened.Level of EvidenceLevel III prognostic study

Whole genome SNP genotyping in a family segregating developmental dysplasia of the hip detected runs of homozygosity on chromosomes 15q13.3 and 19p13.2.

Developmental dysplasia of the hip (DDH) is one of the most prevalent developmental orthopedic diseases worldwide. DDH is a spectrum of anatomical abnormalities of the hip joint and is characterized by premature arthritis in later life. Sporadic cases have been reported more frequently; however, some studies have reported families segregating DDH. Studies have suggested that the genetic factors play a significant role in the development of DDH. In order to detect genetic defect underlying DDH, we performed Sanger sequencing of all DDH associated genes, whole genome SNP genotyping and exome sequencing in a Saudi family with four individuals having DDH. Sanger sequencing of all known genes did not identify any pathogenic variant. Genotype data analysis using HomozygosityMapper identified shared homozygous regions on chromosome 15q13.3 and chromosome 19p13.2 flanked by rs17228178-rs1534200 and rs466123-rs2112461, respectively. These data were also analyzed by cnvpartition software for identification of DDH associated copy number variations (CNV). A shared copy number gain of approximately 15kb on chr6p21.32 (chr6:33053906-33069893) was discovered in all affected individuals. Partial gain of this region has also been found in unaffected sibling of this family. Exome data did not reveal any candidate sequence variant. Whole genome sequencing is required to identify deep intronic variants in the shared homozygous regions. Identification of genetic variants involved in pathogenesis of DDH may open up interesting perspectives into the function of the gene(s) in hip joint development.

Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip

Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner. Moreover, the mRNA level of Scinderin (Scin) considerably increased. We established lentivirus-SCIN(GV144-SCIN) to transfect hBMSCs, which were treated with different Ccs levels (0.25 Hz*5 cm, 0.5 Hz*5 cm, and 1 Hz*10 cm); the result showed that overexpression of Scin upregulated osteogenesis and osteoclastogenesis. By contrast, expression of chondrocyte-specific genes, including ACAN, COL-2A, and Sox9, decreased. Further molecular investigation demonstrated that Scin promoted osteogenesis and osteoclastogenesis through activation of the p-Smad1/5/8, NF-κB, and MAPK P38 signaling pathways, as well as stimulated the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Moreover, Scin-induced osteogenesis outweighed osteoclastogenesis in defective femur in vivo. The results of the analysis of Micro-CT confirmed these findings.Overall, Ccs influenced the development of DDH by promoting osteogenesis and cartilage degradation. In addition, Scin played a vital role in the development of DDH.

Severe cartilage degeneration in patients with developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a developmental disorder that has long-term chronic pain and limited hip joint mobility as major pathological characteristics. This study aims to access the association between the development of DDH and cartilage metabolic disorders. Cartilage tissue samples were acquired from patients with DDH, osteoarthritis (OA) and femoral neck fracture. The proteoglycan level was evaluated by safranin O-fast green, toluidine blue and hematoxylin-eosin (HE) staining. The levels of collagen-II (Col-II), collagen-X (Col-X) and metal matrix proteinase-13 (MMP-13) were evaluated by immunohistochemistry (IHC) and Western blotting analysis. The morphologic evaluation of cartilage was conducted by transmission electron microscopy (TEM). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA level of aggrecan, Col-II, Col-X and MMP-13. The aggrecan level in the cartilage matrix was significantly decreased in DDH patients by safranin O-fast green and toluidine blue staining in comparison with that in the OA and control groups. In contrast with the OA group, the Col-II expression was reduced while the MMP-13 expression increased in DDH patients, as shown by IHC and Western blotting analysis. The collagenous fibrils in cartilage of DDH patients appeared significantly sparse and disordered in the TEM analysis. In DDH patients, the mRNA expression levels of Col-II and aggrecan were markedly reduced, while the mRNA expression of Col-X was markedly increased, compared with the OA patients. There is severe articular cartilage degeneration in DDH patients. This observation provides us with new insight into cartilage metabolic regulation in DDH. © 2017 IUBMB Life, 69(3):179-187, 2017.

A review of environmental factors implicated in human developmental dysplasia of the hip.

PurposeDevelopmental dysplasia of the hip (DDH) is common, and the term encompasses a spectrum of anatomical abnormalities of the hip in which the femoral head displaces from the acetabulum. These abnormalities may be congenital or develop during infancy and/or childhood. Neither the prenatal and postnatal factors that predispose to hip instability nor the determinants of its resolution or persistence are well characterised. A multifactorial pathogenesis of DDH is commonly accepted and identified risk factors include a family history, being first born, breech presentation, female gender, high birth weight and oligohydramnios 1. Further to genetic factors, a number of nutritional, hormonal and mechanical influences on ligament laxity have been hypothesised.MethodsA comprehensive search was conducted using NICE Healthcare Databases Advanced Search and Google Scholar engines, and the terms “nutrition”, “environmental”, “risk factors”, “CDH” and “DDH”. Wherever possible, evidence from randomised controlled trials, systematic reviews and expert review articles published in the medical and veterinary literature was considered.ResultsThe relationship between a number of hormones and biochemical markers of nutritional status and the development of DDH has been repeatedly hypothesised upon in the last 45 years. Of those most frequently cited are calcium, vitamins C and D, and relaxin hormone. The evidence for these potential risk factors is provided mainly by canine studies, with a paucity of consistent or strong evidence in humans.ConclusionsDDH is common and remains a leading cause of hip osteoarthritis in young adults. Neonatal clinical screening programmes for this condition have been in practice since the 1950s, albeit with varying levels of sensitivity. This review summarises current understanding of some of the most frequently cited nongenetic hypothesised risk factors, the significance of which remain to be determined.

To swaddle, or not to swaddle? paleoepidemiology of developmental dysplasia of the hip and the swaddling dilemma among the indigenous populations of North America

Clinical prevalence of developmental dysplasia of the hip (DDH) is high among modern indigenous populations of North America, yet no systematic study of the paleoepidemiology of this group exists. This study discusses the skeletal criteria, epidemiology, pathophysiology, and risk factors of DDH. A range of cases of DDH from an archaeological Native American population are described and the clinical and prehistoric prevalence of DDH among indigenous populations of North America are calculated and discussed within a biocultural perspective. Pelves of 390 adults from the Late Prehistoric (1490 B.P. ± 70) Buffalo site, West Virginia, were examined for DDH. Morphology of true and false acetabula was classified and other changes of the pelvis, lower limb, and spine were noted along with cranial deformation, providing evidence of infant restriction. Prevalence of DDH among living and archaeological indigenous peoples of North America were calculated and compared. Cranial deformation was assessed as evidence for swaddling. DDH was identified in 18 adults from Buffalo, resulting in a minimum prevalence of 46.15 per 1,000, within the range reported in modern indigenous groups in North America. Most, but not all, of the DDH cases were associated with cranial deformation, but not all cases of cranial deformation were associated with DDH. The etiology of DDH suggests that components of both genetic predisposition and swaddling practices have combined to create a high-risk environment for the development of DDH, contributing to high prevalence within archaeological populations, like Buffalo, and modern Indigenous groups of North America.

Retracted: Joined at the hip? A paleoepidemiological study of developmental dysplasia of the hip and its relation to swaddling practices among indigenous peoples of North America

Clinical prevalence of developmental dysplasia of the hip (DDH) is the highest among modern indigenous populations of North America, yet no systematic study of the paleoepidemiology of this group exists. This study discusses the skeletal criteria, epidemiology, pathophysiology, and risk factors for DDH. A range of cases of DDH from an archaeological Native American population are described, and the clinical and prehistoric prevalence of DDH among indigenous populations of North America are calculated and discussed within a biocultural perspective. Pelves of 390 adults from the Late Prehistoric (1490 BP ± 70) Buffalo site, West Virginia were examined for DDH. Morphology of true and false acetabula was classified and other changes of the pelvis, lower limb, and spine were noted along with cranial deformation, providing evidence of infant restriction. Prevalence of DDH among living and archaeological indigenous peoples of North America were calculated and compared. DDH was identified in eighteen adults from Buffalo, resulting in a prevalence of 46.15, within the range reported in modern indigenous groups in North America. However, there is a significant difference between the DDH prevalence in prehistory and today in the target population. Indigenous peoples of North America have the highest reported global prevalence of DDH today and in prehistory. The etiology of DDH suggests that components of both genetic predisposition and swaddling practices have combined to create a high-risk environment for the development of DDH, contributing to its high prevalence within archaeological populations, like Buffalo, and modern Native American/Aboriginal groups within North America.

Variations of theCOL1A1Gene Promoter and the Relation to Developmental Dysplasia of the Hip

Developmental dysplasia of the hip (DDH) is one of the most common hip deformities in children. Since the COL1A1 gene is located in the DDH relating region, we investigated the COL1A1 promoter variations in the development of DDH. We collected 154 unrelated female patients and 180 matched healthy female children, and then sequenced the COL1A1 gene promoter for detection of variations. Three variations in the COL1A1 gene promoter were detected in ten patients (T-139C, C-106T, and C-35T [rs113647555]), but none of the 180 health controls. The chi-square test showed that the rate of total variations in COL1A1 gene contributed to DDH (p=0.0016). We detected three variations in the COL1A1 gene promoter in patients and first demonstrated that the higher rate of total variations of COL1A1 gene contributed to DDH in Chinese female children; thus, the COL1A1 gene is a new candidate gene for DDH disease.

Differences in risk factors between early and late diagnosed developmental dysplasia of the hip

Background: Developmental dysplasia of the hip (DDH) is common, affecting 7.3 per 1000 births in South Australia. Clinical screening programmes exist to identify the condition early to gain the maximum...

Mechanobiological predictions of growth front morphology in developmental hip dysplasia

Developmental dysplasia of the hip (DDH) is the most common orthopedic problem of newborn children. Most clinicians and researchers agree that the primary cause of DDH is abnormal mechanical forces on the head of the femur due to limb position, pressure from the womb, or ligament laxity. The abnormal mechanical forces result in altered growth and bony deformities, in particular large neck-shaft and anteversion angles in the proximal femur and a shallow acetabulum. Previous studies have suggested that intermittent octahedral shear stress promotes growth and ossification, while intermittent hydrostatic compressive stress inhibits growth and ossification. We implemented these mechanobiological principles into a finite element model to predict the rate of progression of the growth front and the formation of coxa valga (large neck-shaft angle) in DDH. Under the assumed normal fetal loading conditions the hydrostatic stress was even across the growth front, but the octahedral shear stress was higher in the center than at the edges. This stress profile promoted growth in the center and a produced a convex growth front shape. Under loading conditions of the dysplastic hip, the octahedral shear stress was much larger on the medial side than on the lateral side, which promoted growth on the medial side and resulted in coxa valga. These results indicate that abnormal forces on the prenatal hip might influence total bone morphology and the development of DDH. These findings might help in understanding the etiology and pathology of other developmental bone deformities.