Quantifying the tolerance of chick hip joint development to temporary paralysis and the potential for recovery.

BACKGROUND: Abnormal fetal movements are implicated in joint pathologies such as arthrogryposis and developmental dysplasia of the hip (DDH). Experimentally induced paralysis disrupts joint cavitation and morphogenesis leading to postnatal abnormalities. However, the developmental window(s) most sensitive to immobility-and therefore the best time for intervention-have never been identified. Here, we systematically vary the timing and duration of paralysis during early chick hip joint development. We then test whether external manipulation of immobilized limbs can mitigate the effects of immobility. RESULTS: Timing of paralysis affected the level of disruption to joints, with paralysis periods between embryonic days 4 and 7 most detrimental. Longer paralysis periods produced greater disruption in terms of failed cavitation and abnormal femoral and acetabular geometry. External manipulation of an immobilized limb led to more normal morphogenesis and cavitation compared to un-manipulated limbs. CONCLUSIONS: Temporary paralysis is detrimental to joint development, particularly during days 4 to 7. Developmental processes in the very early stages of joint development may be critical to DDH, arthrogryposis, and other joint pathologies. The developing limb has the potential to recover from periods of immobility, and external manipulation provides an innovative avenue for prevention and treatment of developmental joint pathologies.

Morphofunctional and ultrastructural evaluation of hip joint development in human fetuses / Evaluación morfofuncional y ultraestructural del desarrollo de la articulación de la cadera en fetos humanos

SUMMARY: The normal sequential development of the hip joint (HJ) was considered for the evaluation of the morphological and ultrastructural aspects of the joint cartilage of the proximal femoral head epiphysis in human fetuses between 16 to 31 weeks of intra uterine life (IUL). Twenty human fetuses were fixed in 10 % formalin solution. Fetuses were divided into 4 groups (n=5): Group 1 (G1): 16-19 weeks IUL; Group 2 (G2): 20-23 weeks IUL; Group 3 (G3): 24-27 weeks IUL and Group 4 (G4): 28-31 weeks IUL. The right moieties of the HJ were subjected to light microscopy to determine the chondrocyte area, volume, and density and the extracellular matrix (ECM) density. The collagen component in ECM was qualitatively evaluated using Safranin-O and picrosirius techniques under polarized light. The left portions were analyzed using scanning electron microscopy (SEM). The advance of age revealed a gradual increase in chondrocyte area and volume and in ECM density, and a decrease in chondrocyte density. The apparent prevalence of type II collagen fibers in G1 and type III collagen fibers in G4, as well as a balance between type I and III collagen fibers in G2 and G3 suggest a process of cartilaginous evolution and repair. The pantographic organization of the collagen fiber meshes from the depth to the cartilage surface of the femoral head suggests that the arcade collagen network architecture starts at the fetal stage, regardless of the compressive forces applied. The morphological data may contribute not only to a better understanding of the maturation and cartilage organization in this area but also to serve as a theoretical basis for aspects related to diseases and joint malformations.

RESUMEN: El desarrollo secuencial normal de la articulación de la cadera (AC) se consideró para la evaluación de los aspectos morfológicos y ultraestructurales del cartílago articular de la epífisis proximal y de la cabeza femoral en fetos humanos entre 16 y 31 semanas de vida intrauterina (SVIU). Veinte fetos humanos fueron fijados en solución de formalina al 10 %. Los fetos se dividieron en 4 grupos (n = 5): Grupo 1 (G1), 1619 semanas de IUL; Grupo 2 (G2), 20-23 semanas SVIU; Grupo 3 (G3), 24-27 semanas SVIU y Grupo 4 (G4), 28-31 semanas SVIU. Las muestras derechas de la AC se sometieron a microscopía óptica para determinar el área, el volumen y la densidad de los condrocitos y la densidad de la matriz extracelular (MEC). El componente de colágeno en la MEC se evaluó cualitativamente utilizando técnicas de safranina-O y picrosirius bajo luz polarizada. Las muestras de la AC izquierda se analizaron utilizando microscopía electrónica de barrido (MEB). El avance de la edad reveló un aumento gradual en el área y el volumen de los condrocitos y en la densidad de la MEB, y una disminución en la densidad de los condrocitos. La aparente prevalencia de las fibras de colágeno tipo II en G1 y tipo III en G4, así como el equilibrio entre las fibras de colágeno tipo I y III en G2 y G3 sugieren un proceso de evolución y reparación cartilaginosa. La organización pantográfica de las mallas de fibra de colágeno desde la profundidad a la superficie del cartílago de la cabeza femoral sugiere que la arquitectura de la red de colágeno comienza en la etapa fetal, independientemente de las fuerzas compresivas aplicadas. Los datos morfológicos pueden contribuir no solo a una mejor comprensión de la organización de la maduración y el cartílago en esta área, sino también servir de base teórica para los aspectos relacionados con enfermedades y malformaciones articulares.

Changes in Proximal Femoral Shape During Fetal Development.

BACKGROUND: Walker and Goldsmith's classic article on fetal hip joint development reported that neck/shaft angle did not change from 12 weeks of gestational age through term while version increased from 0 to 40 degrees. This suggests no change in coronal alignment during development, a conclusion we dispute. By re-examining their data, we found that the true neck/shaft angle (tNSA) decreased by 7.5 degrees as version increased by 40 degrees from 12 weeks of gestational age to term. METHODS: Four investigators measured both femoral version and neck-shaft angle from photographs published by the authors of femurs at multiple stages of maturation from 12 weeks of gestational age to term. The tNSAs and inclination angles were calculated for each femur illustrated using previously validated formula. Changes in the morphology of the femur over time were analyzed using a Student t test. Interobserver and intraobserver reliability were also determined by the Pearson R coefficient. RESULTS: As reported by Walker and Goldsmith, apparent neck/shaft angle (aNSA) did not significantly change during maturation, whereas version increased by 40 degrees. However, tNSA decreased by 7.5 degrees during maturation, while the inclination increased by 32 degrees over the same period. This paper demonstrates angular changes in both the coronal and transverse planes with a 4:1 ratio of angular change in the transverse and coronal planes respectively. Interobserver Pearson coefficient R=0.98 and an intraobserver Pearson coefficient R=0.99. CONCLUSIONS: Although Walker and Goldsmith reported angular changes only in the transverse plane, we conclude that they identified angular changes in both the coronal and transverse planes. Here we show it is mathematically necessary for tNSA to decrease, if aNSA remains constant as version increases. CLINICAL RELEVANCE: A reader who is not well versed in the difference between aNSA and tNSA or version and inclination cannot appreciate what Walker and Goldsmith presented. Surgeons operating on the proximal femur also benefit from understanding these distinctions.

Tensor fasciae latae muscle in human embryos and foetuses with special reference to its contribution to the development of the iliotibial tract.

BACKGROUND: The human tensor fasciae latae muscle (TFL) is inserted into the iliotibial tract and plays a critical role in lateral stabilisation of the hip joint. We previously described a candidate of the initial iliotibial tract that originated from the gluteus maximus muscle and extended distally. MATERIALS AND METHODS: This study extended our observations by examining 30 human embryos and foetuses of gestational age (GA) 7-14 weeks (crown-to-rump length 24-108 mm). At GA 7 weeks, the TFL appeared as a small muscle mass floating in the subcutaneous tissue near the origins of the gluteus medius and rectus femoris muscles. RESULTS: Subsequently, the TFL obtained an iliac origin adjacent to the rectus femoris tendon, but the distal end remained a tiny fibrous mass on the vastus lateralis muscle. Until GA 10 weeks, the TFL muscle fibres were inserted into a vastus lateralis fascia that joined the quadriceps tendon distally. The next stage consisted of the TFL muscle belly "connecting" the vastus fascia and the gluteus fascia, including our previous candidate of the initial iliotibial tract. Until GA 14 weeks, the TFL was sandwiched by two laminae of the connecting fascia. CONCLUSIONS: These findings suggested that, when the vastus lateralis fascia separated from the quadriceps tendon to attach to the tibia, possibly after birth, the resulting iliotibial tract would consist of a continuous longitudinal band from the gluteus maximus fascia, via the vastus fascia, to the tibia. Although it is a small muscle, the foetal TFL plays a critical role in the development of the iliotibial tract.

Foetal development of the human gluteus maximus muscle with special reference to its fascial insertion.

The human gluteus maximus muscle (GMX) is characterised by its insertion to the iliotibial tract (a lateral thick fascia of the thigh beneath the fascia lata), which plays a critical role in lateral stabilisation of the hip joint during walking. In contrast, in non-human primates, the GMX and biceps femoris muscle provide a flexor complex. According to our observations of 15 human embryos and 11 foetuses at 7-10 weeks of gestation (21-55 mm), the GMX anlage was divided into 1) a superior part that developed earlier and 2) a small inferior part that developed later. The latter was adjacent to, or even continuous with, the biceps femoris. At 8 weeks, both parts inserted into the femur, possibly the future gluteal tuberosity. However, depending on traction by the developing inferior part as well as pressure from the developing major trochanter of the femur, most of the original femoral insertion of the GMX appeared to be detached from the femur. Therefore, at 9-10 weeks, the GMX had a digastric muscle-like appearance with an intermediate band connecting the major superior part to the small inferior mass. This band, most likely corresponding to the initial iliotibial tract, extended laterally and distally far from the muscle fibres. The fascia lata was still thin and the tensor fasciae latae seemed to develop much later. It seems likely that the evolutionary transition from quadripedality to bipedality and a permanently upright posture would require the development of a new GMX complex with the iliotibial tract that differs from that in non-human primates. (Folia Morphol 2018; 77, 1: 144-150).

Finite element analysis of mechanical behavior of human dysplastic hip joints: a systematic review.

Developmental dysplasia of the hip (DDH) is a common condition predisposing to osteoarthritis (OA). Especially since DDH is best identified and treated in infancy before bones ossify, there is surprisingly a near-complete absence of literature examining mechanical behavior of infant dysplastic hips. We sought to identify current practice in finite element modeling (FEM) of DDH, to inform future modeling of infant dysplastic hips. We performed multi-database systematic review using PRISMA criteria. Abstracts (n = 126) fulfilling inclusion criteria were screened for methodological quality, and results were analyzed and summarized for eligible articles (n = 12). The majority of the studies modeled human adult dysplastic hips. Two studies focused on etiology of DDH through simulating mechanobiological growth of prenatal hips; we found no FEM-based studies in infants or children. Finite element models used either patient-specific geometry or idealized average geometry. Diversities in choice of material properties, boundary conditions, and loading scenarios were found in the finite-element models. FEM of adult dysplastic hips demonstrated generally smaller cartilage contact area in dysplastic hips than in normal joints. Contact pressure (CP) may be higher or lower in dysplastic hips depending on joint geometry and mechanical contribution of labrum (Lb). FEM of mechanobiological growth of prenatal hip joints revealed evidence for effects of the joint mechanical environment on formation of coxa valga, asymmetrically shallow acetabulum and malformed femoral head associated with DDH. Future modeling informed by the results of this review may yield valuable insights into optimal treatment of DDH, and into how and why OA develops early in DDH.

Effects of normal and abnormal loading conditions on morphogenesis of the prenatal hip joint: application to hip dysplasia.

Joint morphogenesis is an important phase of prenatal joint development during which the opposing cartilaginous rudiments acquire their reciprocal and interlocking shapes. At an early stage of development, the prenatal hip joint is formed of a deep acetabular cavity that almost totally encloses the head. By the time of birth, the acetabulum has become shallower and the femoral head has lost substantial sphericity, reducing joint coverage and stability. In this study, we use a dynamic mechanobiological simulation to explore the effects of normal (symmetric), reduced and abnormal (asymmetric) prenatal movements on hip joint shape, to understand their importance for postnatal skeletal malformations such as developmental dysplasia of the hip (DDH). We successfully predict the physiological trends of decreasing sphericity and acetabular coverage of the femoral head during fetal development. We show that a full range of symmetric movements helps to maintain some of the acetabular depth and femoral head sphericity, while reduced or absent movements can lead to decreased sphericity and acetabular coverage of the femoral head. When an abnormal movement pattern was applied, a deformed joint shape was predicted, with an opened asymmetric acetabulum and the onset of a malformed femoral head. This study provides evidence for the importance of fetal movements in the prevention and manifestation of congenital musculoskeletal disorders such as DDH.

Human fetal topographical anatomy of the femoral triangle in relation with change in the hip joint position.

Fetal hip joint is characterized by its highly flexion and lateral rotation although adult anatomy of the femoral nerve and iliofemoral ligament suggested the medial rotation. To investigate topographical anatomy of the femoral nerve, artery and vein in the femoral triangle, we histologically examined 11 fetuses (15-37 weeks). The nerve-vessel topographical relation was basically similar to that in adults, but the fan-like nerve division was seen in the horizontal plane in the smaller specimens in contrast to that included in the sagittal plane in the larger specimens. The medial or internal rotation of the nerve division seemed to occur in late stage fetuses, at birth and at infancy. Blood supply to the head of the femur might be also accelerated by changes in the hip joint position.

Immobilized chicks as a model system for early-onset developmental dysplasia of the hip.

We have almost no understanding of how our joints take on their range of distinctive shapes, despite the clinical relevance of joint morphogenesis to postnatal skeletal malformations such as developmental dysplasia of the hip (DDH). In this study, we investigate the role of spontaneous prenatal movements in joint morphogenesis using pharmacological immobilization of developing chicks, and assess the system as a suitable model for early-onset hip dysplasia. We show that, prior to joint cavitation, the lack of dynamic muscle contractions has little impact on the shape of the hip joint. However, after the timepoint at which cavitation occurs, a dramatic effect on hip joint morphogenesis was observed. Effects in the immobilized chicks included flattening of the proximal femur, abnormal orientation of the pelvis relative to the femur and abnormal placement and coverage of the acetabulum. Although many clinical case studies have identified reduced or restricted movement as a risk factor for DDH, this study provides the first experimental evidence of the role of prenatal movements in early hip joint development. We propose that the immobilized chick embryo serves as a suitable model system for the type of early-onset DDH which arises due to neuromuscular conditions such as spinal muscular atrophy.

Joint shape morphogenesis precedes cavitation of the developing hip joint.

The biology and mechanobiology of joint cavitation have undergone extensive investigation, but we have almost no understanding of the development of joint shape. Joint morphogenesis, the development of shape, has been identified as the 'least understood aspect of joint formation' (2005, Birth Defects Res C Embryo Today 75, 237), despite the clinical relevance of shape morphogenesis to postnatal skeletal malformations such as developmental dysplasia of the hip. In this study, we characterise development of early hip joint shape in the embryonic chick using direct capture 3D imaging. Contrary to formerly held assumptions that cavitation precedes morphogenesis in joint development, we have found that the major anatomical features of the adult hip are present at Hamburger Hamilton (HH)32, a full day prior to cavitation of the joint at HH34. We also reveal that the pelvis undergoes significant changes in orientation with respect to the femur, despite the lack of a joint cavity between the rudiments. Furthermore, we have identified the appearance of the ischium and pubis several developmental stages earlier than was previously reported, illustrating the value and importance of direct capture 3D imaging.

Development of human hip joint in the second and the third trimester of pregnancy; a cadaveric study.

BACKGROUND: The purpose of the study was an evaluation of fetal hip joint morphology during the second and the third trimester of pregnancy. Serial sections were performed on 23 cadaver infants. RESULTS: The mean lunar age was 6.6 months. Femoral shaft length (FSL) and width of the proximal and distal epiphysis were x-rayed to determine fetal age. The neck shaft angle (NSA), the femoral antetorsion angle (FAA), the acetabulum anteversion angle (AAA) and the acetabulum slope angle (ASA) were measured. Hip development ratios were plotted for all cadaveric species and revealed: flat FSL/NSA slope pattern, upward FSL/FAA slope pattern and downward slope pattern for FSL/ASA and FSL/AAA ratios. The changes, observed during the developmental period, were not statistically significant. NSA did not change during the second or the third pregnancy trimester. FAA increased during pregnancy but the changes were not statistically significant. AA, as well as ASA, showed a decreasing trend during the second and the third pregnancy trimester, however, with no correlations to age. CONCLUSION: Despite an increasing depth and growing dimensions of the acetabulum in the uterus, its orientation does not change in any significant way.

Morphometric and ultrasonographic study of the human fetal hip joint during intrauterine development.

UNLABELLED: The main method for the early screening of the developmental dysplasia of the hip (DDH) is the ultrasound imaging. There are several studies about the ultrasound imaging of newborns' hips, but only a few studies include the prenatal period of life. Our aim was to examine the prenatal development of the hip joint through the evolution of the α angle seen on the ultrasound, described in the Graf R method, combined with anatomical dissection. MATERIALS AND METHODS: Thirty-one post-mortem fetal hips were analyzed trough anatomical dissection, in 25 cases trough ultrasound imaging, in which the α angle was measured. Based on the morphometric examination, we applied the sine rule and we calculated the α1 angle, which also represents the coverage of the femoral head. RESULTS: Based on the morphometric examination, not only the diameters of the femoral head and of the acetabulum, but also the joint cavity (X) showed an increase during development. Both of the α angles (measured α, calculated α1) showed a decrease as the fetus developed. CONCLUSIONS: The decrease of the angles (α, α1) and the increase of the joint cavity during development correspond to the findings of the main research papers: the hip joint is less stable in the perinatal life. The α angle can be accurately determined only after the ossification of the acetabulum had started, in our case after the fetus is older than 18 weeks.

Vascularity and histology of fetal labrum and chondrolabral junction: its relevance to chondrolabral detachment tears.

PURPOSE: Recently, acetabular labral tears were recognized as a source of hip pain. Most of these tears were found to be localized at the chondrolabral junction. The purpose of this study was to evaluate the chondrolabral junction in reference to its collagen fiber orientation and its vascularity, which might be used to explain the preponderance of labral tears. METHODS: Eighteen formalinized fetuses with a mean gestational age of 17 weeks (range: 11-24 weeks) were examined. The acetabuli were removed en bloc with the proximal femur for ease of orientation. The acetabuli were prepared and examined in four quadrants, namely, anterior, superior, posterior, and inferior. RESULTS: The staining pattern of the posteroinferior labrum was more dense than the anterosuperior labrum, due to its high collagen content. Collagen fibers in the posteroinferior quadrants were oriented perpendicularly to the chondrolabral junction, while those in the anterosuperior quadrants had a parallel oriented. Perpendicular collagen orientation and high collagen content may explain the stronger anchorage of the labrum to the bony acetabulum in posteroinferior quadrants. All of the vessels supplying the labrum originate from the capsular connective tissue and traverse the body of the labrum to reach the articular side. None of these vessels traverse the chondrolabral junction to reach the bony acetabulum. The total number of blood vessels was significantly higher in the capsular zone than in the articular zones. The number of blood vessels did not differ between the acetabular quadrants. CONCLUSIONS: In an effort to understand the chondrolabral junction tears, we can conclude that collagen content and fiber orientation may represent the histological basis for the predominance of tears at the anterosuperior region.

An approach to comparative anatomy of the acetabulum from amphibians to primates.

The objective of this study was to investigate the anatomy, both macroscopic and microscopic, of the soft tissue internal structures of the hip joint in animal species and in three human hips (an adult and two fetuses). We dissected the hip joints of 16 species and compared the anatomical features of the soft tissue from the respective acetabula. In addition, a histological study was made of the specimens studied. In amphibians, we found a meniscus in the acetabulum, which was not observed in any of the other species studied. The isolated round ligament is observed from birds onwards. In the group of mammals analysed, including the human specimens, we found a meniscoid structure in the acetabular hip joint. Furthermore, we found that the meniscoid structure forms an anatomo-functional unit with the round ligament and the transverse ligament of the coxofemoral joint. These discoveries suggest the participation of the soft tissue anatomy in adaptative changes of species.

The labro-acetabular complex.

The human hip is subjected to several hundred million loading cycles during a lifetime. Hip instability and femoro-acetabular impingement cause damage to the rim of the acetabulum. The acetabular rim is a highly specialized structure known as the labro-acetabular complex. A unidirectional flow of synovial fluid has been identified in this region. The synovial fluid circulation is driven by the bellows-like movement of the zona orbicularis and depends on hip flexion and extension. Surgical repair of the damaged labro-acetabular complex should satisfy two goals. First, the labrum should be preserved or reconstructed when possible. Second, the precipitating cause of the labro-acetabular damage must be addressed.

Vascularity of the hip labrum during the foetal period.

Tears of the hip labrum have been recognized as a cause of hip pain and clicking. It has been reported that labrum tears are associated with increased microvessel formation. The purpose of this study was to identify the regional vascularity of the acetabular labrum during late foetal development. The acetabular labrum was examined from 21 formalinized foetuses of the age 5th to 10th months of gestation (mean 6.4±0.99). The acetabulum of each specimen was anatomically prepared and divided into four quadrants. The number of blood vessels in labrum quadrants was counted during microscopic examination. A total of 599 of blood vessels were found in all specimens: 159 in quadrant I, 150 in quadrant II, 127 in quadrant III and 163 in quadrant IV. The capsular part of the labrum contained 357 vessels and the articular part contained 242. The total number of blood vessels within the capsular parts of all specimens (357) was significantly greater than the number within the articular parts (242) (p<0.028). There was some evidence to suggest that with increasing foetal age, the number of blood vessels in the labrum decreased. However, taking into consideration the number of vessels in particular quadrants of the labrum, the great frequency of labral tears in the anterosuperior part of the labrum could not be explained.

Measuring hip development using magnetic resonance imaging.

BACKGROUND: Abnormal hip development can have severe consequences if not detected and treated early. Previous studies have shown that if the abnormality is detected early, the outcome is good. Much is known about embryological hip development (weeks 1-10 after conception) from postmortem examination. For ethical reasons, information about hip development in the fetal stage of pregnancy (10 weeks to term) is less certain as it is largely gained from animal studies and from early radiograph studies. A few autopsy-based studies have been reported looking at hip development, but no one has shown, to our knowledge, that postmortem magnetic resonance is able to provide the same and possibly more information. The aim of this study was to assess the value of magnetic resonance imaging in providing information on fetal hip development. METHODS: Measurements of 30 patients (gestation, 17-42 weeks) were made regarding the width and depth of the acetabulum and the radius and diameter of the femoral head; volume and area were calculated. RESULTS: With the exception of the acetabular width, each dimension showed little development until week 20 when growth rose exponentially. The acetabular width showed a slow rate of growth, despite changes in the femoral head. Levels of observer agreement were high for all but depth (intraclass correlation coefficients, 0.90). CONCLUSIONS: The measurements were in line with previous postmortem studies. Magnetic resonance imaging is a valid alternative to postmortem in the assessment of hip development. Magnetic resonance imaging has the potential to alert clinicians to the possible abnormal development, allowing early intervention. STUDY DESIGN: Cross-sectional study with purposive sampling.

Digital-image analysis of the femoral shaft/neck angle in human foetuses.

Measurements were made of the femoral shaft/neck angle (CCD angle) in 106 human foetuses, aged from 16 to 38 hbd, using a "FEM-GEO_03" computer program. The values of the CCD angle in the group under examination were: mean = 140.48 degrees, SD = 6.95 degrees, max = 157.90 degrees, min = 113.93 degrees. No significant differences were found in CCD angle size between male and female foetuses or between left and right bones. Dispersion analysis showed a decrease in the CCD angle during foetal development, which suggests that adaptation to a vertical position and bipedal gait starts during pregnancy and is manifest as an inborn feature.

A sonographic study of perinatal hip development: from 34 weeks of gestation to 6 weeks of age.

A sonographic study of perinatal hip development was performed by consecutive measurement of Graf's alpha and beta angles in fetal and newborn hips. The study group consisted of infants with sonographically normal hip findings at birth. Forty fetuses were examined by fetal hip sonography at 34, 36 and 38 weeks of gestation. Postnatally, hip sonography was performed in the first and sixth week of age. Maturation curves of the bony (alpha-angle) and cartilaginous (beta-angle) acetabular roof from 34 weeks of gestation to 6 weeks of age were established. Prenatally, the mean alpha-angles were above the level that corresponds to a mature hip joint. A significantly higher value of the mean alpha-angles was found after birth. The mean beta-angles of the fetuses did not differ from those of the newborns. Our results revealed that the fetal hip joint is sonographically mature at 34 weeks of gestation. Further progression of hip development occurs around term.