Int J Clin Exp Med 2014;7(12): /ISSN: /IJCEM

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1 Int J Clin Exp Med 2014;7(12): /ISSN: /IJCEM Original Article Spatial changes of the peri-acetabular pelvic in developmental dysplasia of the hip---a combined 3-dimentional computed tomography (3D-CT) study in patients and experimental study in rats Cong Shang 1, Tianjing Liu 1, Hengcui Xie 1, Jianjun Li 2, Sizhe Gao 3, Qun Zhao 1, Lijun Zhang 1, Enbo Wang 1 Departments of 1 Pediatric Orthopedics, 2 Orthopedics, 3 Radiology, Shengjing Hospital, China Medical University, Shenyang , Liaoning, P. R. China Received September 19, 2014; Accepted November 24, 2014; Epub December 15, 2014; Published December 30, 2014 Abstract: Few previous studies noticed the three bony structures that formed the acetabulum in developmental dysplasia of the hip (DDH). This study aimed at investigating the spatial changes of the peri-acetabular pelvis in developmental dysplasia of the hip through radiological evaluation of the patients and experimental observations in rat models. 115 unilateral DDH patients were studied through 3D-CT. In reconstruction workstation, the iliopubic inner plate angle, ilioischial inner plate angle and ischialpubic inner plate angle were measured and compared. 58 neonatal Wistar rats were divided into two groups and the rats in experiment group were swaddled to establish DDH models. The hips were sectioned, stained. The same three angles were measured and compared. The ilioischial inner plate angle of the affected hip decreased while the ischialpubic inner plate angle increased compared to those of the contralateral side. The iliopubic inner plate angle showed no difference between the affected and unaffected hips. In animal models we observed the same pathological pattern. The three angles measured on the sections showed similar tendency as those in the patients with DDH. The ischium rotates up and forwardly around the posterior and vertical limbs of the triradiate cartilage complex in DDH, just as a lifted piece of Pizza. Keywords: Developmental dysplasia of the hip, triradiate cartilage complex, 3D-CT, animal model, ischium Introduction The acetabulum of young children is mainly composed of the triradiate cartilage complex (TCC), a conjunct cartilage that lies among the three osseous components of the pelvis (the ilium, ischium, and pubis) [1, 2]. In the natural history of DDH, not only the shape but also the direction of the acetabulum changes in untreated dislocated hip in children [3-5]. Considering the osteogenesis role of the TCC, changes in the TCC or (and) relevant bony changes may contribute to this phenomenon. Relevant articles mainly focused on the acetabulum, through either radiological studies in patients or histological studies in experimental animals. Few of them noticed the three-dimensional relationship between the ilium, pubis and ischium in DDH, let alone the TCC in conjunction of them. In our previous study, we observed both in patients and rat models of DDH that excessive lateral rotation of the ischium resulted in increased acetabular anteversion [6-8]. So we hypothesized that the position of the ischium might display some changes within the hemipelvis of the dislocated hip in DDH. This study combines clinical evaluation of DDH patients through 3D-CT with experimental observation of rat DDH models, aiming at finding out the features of spatial change in ischium in DDH. We hope our study can provide further insight to the pathology of DDH. Materials and methods Radiologic study on clinical subjects We investigated all the patients who had been diagnosed unilateral DDH in our hospital from

2 cases were classified as Tönnis II, 43 cases as Tönnis III and 32 cases as Tönnis IV. The unaffected hips were used as control. Figure 1. Reconstruction images were completed in three section planes. The section plane were through the midpoint of the each branch of TCC and perpendicular to the inner plates of the both adjacent bones concurrently. : Indicates the section plane between the ilium and the ischium....: Indicates the section plane between the ilium and the pubis : Indicates the section plane between the ischium and the pubis. January 2007 to August The inclusion criteria were as follows: (1) the affected hip was diagnosed DDH and the unaffected hip presented no radiographic abnormalities; (2) no treatment before admission to our hospital and (3) complete 3D-CT image data of the patient can be obtained. Before September 2010, 3D-CT was used in our institution to evaluate the femoral neck anteversion (FNA) of the patients with DDH preoperatively. After that, MRI has been utilized instead of CT to evaluate FNA. Patients with neuromuscular diseases or hip dislocation complicated by other congenital malformations were excluded. A total of 115 cases met the criteria, including 76 left dislocations and 39 right dislocations; 16 were male and 99 were female. Age range was from 2 to 9 years, averaging 3 years and 6 months. 40 The patients were examined with the U. S. Marconi Company s Mx8000 type CT. The scan range was from the iliac crest to the lesser trochanter of the femur. Scan parameters: tube voltage ball 120 Kv, current MA, slice thickness 1.0 mm, the interlayer spacing 1.0 mm and pitch mm. Reconstruction and measurement were done in the spiral CT workstation applications (Extended Brilliance [Tm] Workspace) and Display image associated measurement systems (Figure 1). For the iliopubic inner plate angle, the measurement was performed on the plane through the midpoint of the anterior branch of TCC perpendicular to the inner plate of ilium and pubis concurrently. Tangent lines of the inner panel of the ilium and the pubis formed the iliopubic inner plate angle. Similarly, the measurement of the ilioischial inner plate angle and the ischialpubic inner plate angle (Figure 2) were performed and compared. Reconstruction and measurement were performed by two different experienced doctors of department of radiology in our hospital to assess the interobserver variation. One of the observers reconstructed and measured the data the second time a month after the first time to assess the intraobserver variation. And the average of the three results of measurement was used as the final data of each angle to be analyzed. Experimental animal study 58 neonatal Wistar rats from 6 litters were divided into control group (15 females, 10 males) and an experimental group (19 females, 14 males). The experimental group were swaddled with medical tape (3 M Durapore, St.Paul, Minnesota) to keep the hips and knees in extension and lower limbs together for the first ten days of life, as described by E. Wang [8]. The swaddling permitted minor hip and knee movement. The rats were released from the swaddles for thirty minutes per day and rewrapped in accommodation to the growth of their bodies. The rats all fed from their mothers, and care was taken to guarantee their normal intake. After ten days, the swaddles were removed and the rats were allowed unrestricted motion in the cage Int J Clin Exp Med 2014;7(12):

3 Figure 2. Within the reconstructed section plane mentioned in Figure 1, drew tangent lines along the inner panel of ilium, pubis and ischium to form the three inner plate angles. A-C. Showed the iliopubic inner plate angle, ilioischial inner plate angle and pubic-ischial inner plate angle respectively. Table 1. The inner plate angles from radiographic examination of 115 children with unilateral DDH Inner plate angle (n = 115) Affected hips Unaffected hips P-Value Iliopubic ± ± Ilioischial ± ± * Ischialpubic ± ± * All data were presented as mean ± standard deviation. *Indicates statistical significance compared to unaffected controls at P < At the age of 1 month, all rats were euthanized by 5% chloral hydrate. All hips were dissected en bloc, fixed in neutral formalin and decalcified in 10% EDTA (ethylenediaminetetraacetic acid). Rats from two groups were used to observe the iliopubic inner plate angle, the ilioischial inner plate angle and the ischialpubic inner plate angle respectively. Then the samples were embedded in paraffin and sectioned at 4 μm thickness on the same levels as described in 3DCT image data. All the sections were stained with Safranin O-Fast Green (Sigma). Then we measured the three angles on the corresponding sections. Statistical analysis Results Measurement of the radiological parameters listed in Table 1 were the average of three measurements. Difference between the affected and unaffected side of unilateral DDH was significant in the ilioischial inner plate angle and the ischi- alpubic inner plate angle. Gender difference were insignificant in all three parameters, with p = in the ilioischial inner plate angle, p = in the iliopubic inner plate angle and p = in the ischialpubic inner plate angle. Differences in the three angles between the affected and unaffected side were not correlated with age, nor the degrees of dislocation. The results of interobserver variation and intraobserver variation showed the difference between different observers and different time were small enough to be accepted. So the reconstruction and measurement from different observers and in different time were considered to be accordant and repetitive (Tables 2, 3). Statistical analysis was performed with Statistical Package for Social Science 17.0 (SPSS; Chicago, Illinois). Paired sample t-test and independent sample t-test were used to analyze differences between the control group and the experimental group. Independent sample t-test was used to analyze differences between genders. Bivariate correlate were used to study the difference among the degrees of dislocation as well as ages. P < 0.05 was regarded as statistically significant. The interobserver variation and intraobserver variation were analyzed with Bland-Altman by Medcalc (Ostend, Belgium). In the animal study, 3 female rats in the experimental group died during the experiment. Gross observation of the remaining 60 hips rats in the experimental group showed that 48 hips were completely dislocated, 4 hips (all from female rats) were subluxation and 8 hips were normal (6 hips from male rats and 2 hips from female rats). Only the 48 completely dislocated hips were further studied. In the control group, all hips were normal and included in further study. In histological study, we found the ischium of the rats in the experimental group turned forward and upward compared to those in the control group (Figure 3). By measuring the sec Int J Clin Exp Med 2014;7(12):

4 Table 2. The interobserver variation of 3D-CT tions, we also observed that the ilioischial inner plate angles became smaller and the ischialpubic inner plate angles became larger in the experimental group, while there was no statistical difference in the ischialpubic inner plate angle (Figure 4; Table 4). There was no statistic gender difference in these angles, with p = in the ilioischial inner plate angle, p = in the iliopubic inner plate angle and p = in the ischialpubic inner plate angle. Discussion Affected hips Most previous studies on hip morphology focused on the anatomic features of the acetabulum and the femoral head, while few reported on the spatial relationship of the three bones (the ilium, the pubis and the ischium) that form the acetabulum. Relevant researches had been done in clinical studies through X-ray, MRI or 3D-CT [9-12]. Albinana et al. found that the pelvis was asymmetric in anteropsterior radiographs in patients with unilateral DDH and suggested that it was a true pelvic deformity rather than a change in acetabular orientation [9]. Suzuki noticed medial twisting of the pelvis in the affected side of unilateral DDH in threedimension MRI [10]. In our previous radiological study with 3D-CT, we observed rotation of the lower pelvis but no deformity in the upper pelvis [6]. Another study manifested that increased acetabular anteversion might be attributed to excessive lateral rotation of the ischium [7]. Those studies had drawn our attention to the Unaffected hips Bias ± SD Limits of agreement Bias ± SD Limits of agreement Iliopubic -0.2 ± 3.37 (-6.9, 6.4) -0.6 ± 4.59 (-9.6, 8.4) Ilioischial -9.4 ± 8.67 (-26.3, 7.6) -9.8 ± 7.96 (-25.4, 5.8) Ischialpubic -1.5 ± 5.87 (-13.0, 10.0) -0.5 ± 5.77 (-11.7, 10.8) All data were presented as mean ± standard deviation. Bias-average difference, ideal bias = 0. Limits of Agreement describes the range for 95% of comparison points. Table 3. The intraobserver variation of 3D-CT Affected hips Unaffected hips Bias ± SD Limits of agreement Bias ± SD Limits of agreement Iliopubic 1.2 ± 4.85 (-8.3, 10.7) 1.5 ± 3.01 (-4.5, 7.4) Ilioischial -0.4 ± 3.27 (-6.7, 6.0) -0.5 ± 2.96 (-6.3, 5.3) Ischialpubic 0.5 ± 4.59 (-8.5, 9.5) 0.9 ± 4.49 (-8.0, 9.7) All data were presented as mean ± standard deviation. Bias-average difference, ideal bias = 0. Limits of Agreement describes the range for 95% of comparison points. three components of the acetabulum and their specific roles in acetabular deformities. In this study, we used three angles to depict the three-dimensional relationship among the three bones. The ilioischial inner plate angle of the affected hip was significantly reduced compared to the unaffected side (P < 0.01), while the ischialpubic inner plate angle of the affected side was signifi- cantly larger than the unaffected side (P < 0.01). Spatially speaking, the ischium had rotated upward around the axis of the posterior flange of TCC and forward around the axis of the anterior flange of TCC, just as a lifted piece of Pizza (Figure 5). Acetabulum is a three-dimensional structure consisted of the acetabular TCC, articular cartilage and the three bones. These parts should develop proportionally to form a normal acetabulum. Portinaro found by measuring the thickness of epiphyseal plates that in TCC the epiphyseal plate of ischium grew the most quickly, followed by the pubis and the ilium. In other words, the ischium contributed the most to the development of acetabulum, while the ilium contributed less and the pubis the least. Changes in the three-dimensional features of the ischium will significantly influence the morphology of the acetabulum [13]. Harrison reported that the ischial epiphysis which constituted the posterior wall of the acetabulum became disturbed or even stopped growing after manual removal of the femoral head [14]. E. Delgado-Baeza et al. also found that the ilium would turn forward and outward after femoral head dislocation in an analogous animal experiment and hypothesized that it resulted from growth disorders of the triradiate cartilage [15]. But Smith et al. got different results when they investigated dogs and guinea pigs. They attributed this difference to different propor Int J Clin Exp Med 2014;7(12):

5 Figure 3. The gross anatomical observation of the experimental group (A) and the control group (B). Note the remarkably deviated ischium around the dislocated hips (arrows). Figure 4. Safranin O-fast green stained sections ( 20): (A, C, E) were from experimental group and (B, D, F) were from control group. (A, B) were the iliopubic inner plates angle, (C, D) were the ilioischial inner plate angle and (E, F) were the ischialpubic inner plate angle respectively. Note the difference of the ilioischial inner plate angle and the ischialpubic inner plate angle between the experimental and control groups. *Indicates ilium, #Indicates ischium, +Indicates pubis. tions of cartilage tissue in the hips and different susceptibility to deformation among spaces [16]. We designed an animal study to further clarify this issue. Instead of manual dislocation of the femoral head, as described in most previous 4987 Int J Clin Exp Med 2014;7(12):

6 Table 4. The inner plate angle measuring from the rats of the experimental and control group Inner plate angle Dislocated hips group (n = 48) Control group (n = 50) P-Value Iliopubic ± ± Ilioischial ± ± * Ischialpubic ± ± * All data represented as mean ± standard deviation. *Indicates statistical significance compared to untreated controls at P < Figure 5. Spatial change of the ischium. The ischium turns forward and upward slightly around the posterior and vertical limbs of the triradiate cartilage complex respectively in the hip of DDH, just as a lifted piece of Pizza. Normal hip (left) and dislocated hip (right). Our study verified this thesis, both in patients and in animals, and thus made periacetabular osteotomies (innominate osteotomy, triple osteotomy, etc.) that redirected the acetabulum more theoretically reasonable. The ilio-pubic inner plate angle showed no difference between the affected and unaffected hips, both in patients and in animals. We speculated that the sacroiliac joint and the pubic symphysis were firm enough to fix the ilium and pubis in their positions, while the ischium is relatively free and therefore prone to bending. Further investigation is needed to verify the mechanism of this phenomenon. In conclusion, of the three bony components of the acetabulum, the ischium shows the most obvious spatial change in DDH, which may contribute to the change of acetabular direction. The ischium rotates up and forwardly around the posterior and vertical limbs of the TCC respectively, just as a lifted piece of Pizza. reports [14, 15], we used straight-leg swaddling to establish the model in neonatal rats [8] in order to best simulate the pathological process of acetabular dysplasia. Changes in the three angles were similar, with significant decrease in the ilioischial inner plate angle and increase in ischialpubic inner plate angle in the experimental group. These indicated that the pelvic bones (Ilium-Ischium and Pubis-Ischium) bent around the hinge of each limb of the TCC, which was in correspondence with the findings in patients. From the aspect of animal experiment, our findings were somehow similar to those of Cannillas [17], who reported bending and rotation of the ischium in a hip-extension DDH model in rats. Since the days of Salter, it had been suggested that the acetabulum turned antero-laterally in acetabular dysplasia [3, 18, 19], but this finding has not been tested by subsequent studies. Acknowledgements National Natural Science Foundation of China, No ; Disclosure of conflict of interest None. Address correspondence to: Enbo Wang, Department of Pediatric Orthopedics, Shengjing Hospital, China Medical University, Shenyang , Liaoning, P. R. China. Tel: (86) ; wangeb@sj-hospital.org References [1] Ponseti IV. Morphology of the acetabulum in congenital dislocation of the hip: gross, histological and roentgenographic studies. J Bone Joint Surg Am 1978; 60: Int J Clin Exp Med 2014;7(12):

7 [2] Dunn PM. The anatomy and pathology of congenital dislocation of the hip. Clin Orthop 1976; 119: [3] Salter RB. Etiology, pathogenesis and possible prevention of congenital dislocation of the hip. Can Med Assoc J 1968; 98: [4] Sarban S, Ozturk A, Tabur H and Isikan UE. Anteversion of the acetabulum and femoral neck in early walking age patients with developmental dysplasia of the hip. J Pediatr Orthop B 2005; 14: [5] Aminian A, Mahar A, Yassir W, Newton P and Wenger D. Freedom of acetabular fragment rotation following three surgical techniques for correction of congenital deformities of the hip. J Pediatr Orthop B 2005; 25: [6] Jia J, Zhang L, Zhao Q, Li L and Liu X. Does medial rotational deformity of the whole pelvis universally exist in unilateral DDH? Arch Orthop Trauma Surg 2011; 131: [7] Jia J, Li L, Zhang L, Zhao Q, Wang E and Li Q. Can Excessive Lateral Rotation of the Ischium Result in Increased Acetabular Anteversion? A 3D-CT Quantitative Analysis of Acetabular Anteversion in Children With Unilateral Developmental Dysplasia of the Hip. J Pediatr Orthop 2011; 31: [8] Wang E, Liu T Li J, Edmonds Ew, Zhao Q, Zhang L, Zhao X and Wang K. Does swaddling influence developmental dysplasia of the hip? an experimental study of the traditional straightleg swaddling model in neonatal rats. J Bone Joint Surg Am 2012; 94: [9] Albiñana J, Morcuende JA, Delgado E and Weinstein SL. Radiologic pelvic asymmetry in unilateral late diagnosed developmental dysplasia of the hip. J Pediatr Orthop 1995; 15: [10] Suzuki S. Deformity of the pelvis in developmental dysplasia of the hip: three-dimensional evaluation by means of magnetic resonance image. J Pediatr Orthop 1995; 15: [11] Lin CJ, Romanus B, Sutherland DH, Kaufman K, Campbell K and Wenger DR. Three-Dimensional characteristics of cartilaginous and bony components of dysplastic hips in children: three-dimensional computed tomography quantitative analysis. J Pediatr Orthop 1997; 17: [12] Kim HT, Wenger DR. The morphology of residual acetabular deficiency in childhood hip dysplasia: three-dimensional computed tomographic analysis. J Pediatr Orthop 1997; 17: [13] Portinaro NM, Murray DW and Benson MK. Microanatomy of the acetabular cavity and its relation to growth. J Bone Joint Surg Br 2001; 83: [14] Harrison TJ. The influence of the femoral head on pelvic growth and acetabular from in the rat. Journal of anatomy. J Anat 1961; 95: [15] Delgado-Baeza E, Albiñana-Cilveti J and Miralles-Flores C. Why Does Pelvic Deformity Occur in experimental dislocation of the growing Hip? J Pediatr Orthop 1992; 12: [16] Smith WS, Ireton RJ and Coleman CR. Sequelae of experimental dislocation of a weightbearing ball- and socket joint in a young growing animal; gross alterations in bone and cartilage. J Bone Joint Surg Am 1958; 40: [17] Canillas F, Delgado-Martos MJ, Martos-Rodriguez A, Quintana-Villamandos B and Delgado- Baeza E. Contribution to the initial pathodynamics of Hip luxation in Young Rats. J Pediatr Orthop 2012; 32: [18] Salter RB. Innominate osteotomy in treatment of congenital dislocation of the hip. J Bone Joint Surg Br 1961; 43: 72. [19] Salter RB. Role of innominate osteotomy in the treatment of congenital dislocation and subluxation of the hip in the older child. J Bone Joint Surg Am 1966; 48: Int J Clin Exp Med 2014;7(12):