Hydrolysis reaction promotes changes in coordination mode of Ru(II)/acylthiourea organometallic complexes with cytotoxicity against human lung tumor cell lines.

RESEARCH ARTICLE Hip stress distribution - Predictor of dislocation in hip arthroplasties. A retrospective study of 149 arthroplasties Matevž Tomaževič ID1,2*, Tina Kaiba1, Urban Kurent2, Rihard Trebše3, Matej Cimerman2, Veronika Kralj-Iglič1 1 Laboratory of Clinical Biophysics, Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia, 2 Department of Traumatology, Division of Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia, 3 Orthopaedic Hospital Valdoltra, Ankaran, Slovenia a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Tomaževič M, Kaiba T, Kurent U, Trebše R, Cimerman M, Kralj-Iglič V (2019) Hip stress distribution - Predictor of dislocation in hip arthroplasties. A retrospective study of 149 arthroplasties. PLoS ONE 14(11): e0225459. https://doi.org/10.1371/journal.pone.0225459 Editor: Daniel Pérez-Prieto, Consorci Parc de Salut MAR de Barcelona, SPAIN Received: June 3, 2019 Accepted: November 5, 2019 Published: November 20, 2019 Copyright: © 2019 Tomaževič et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. * matevz.tomazevic@kclj.si Abstract Dislocation after hip arthroplasty is still a major concern. Recent study of the volumetric wear of the cup has suggested that stresses studied in a one-legged stance model could predispose arthroplasty dislocation. The aim of this work was to study whether biomechanical parameters of contact stress distribution in total hip arthroplasty during a neutral hip position can predict a higher possibility of the arthroplasty dislocating. Biomechanical parameters were determined using 3-dimensional mathematical models of the one-legged stance within the HIPSTRESS method. Geometrical parameters were measured from standard anteroposterior X-ray images of the pelvis and proximal femora. Fifty-five patients subjected to total hip arthroplasty that later suffered dislocation of the head and, for comparison, ninety-four total hip arthroplasties that were functional at least 10 years after the implantation, were included in the study. Arthroplasties that suffered dislocation had on average a 6% higher resultant hip force than the control group (p = 0.004), 11% higher peak stress on the load-bearing area (p = 0.001) and a 50% more laterally positioned stress pole (p = 0.026), all parameters being less favorable in the group of unstable arthroplasties. There was no statistically significant difference in the gradient index or in the functional angle of the weight bearing. Our study showed that arthroplasties that show a tendency to push the head out of the cup in the representative body position—the one-legged stance—are prone to dislocation. An unfavorable resultant hip force, peak stress on the load bearing and laterally positioned stress pole are predictors of arthroplasty dislocation. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: The study was funded by the Slovenian Research Agency grant P3-0388 to VK-I. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Introduction Based on patient reported outcome measures, hip arthroplasty is the most successful elective surgical procedure [1]. Thanks to efforts to design and produce an optimal prosthesis offering long-term functionality, more than 95% of arthroplasties survive more than 10 years [2,3]. Some total hip arthroplasties (THAs) nevertheless fail and revision surgery is needed. Hip PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 1 / 13 Hip stress arthroplasty dislocation predictor dislocation after THA is the second most common cause of revision surgery [2]. The reported rate of revision due to dislocation after primary THA is 2–4% in the first six months [4] and increases to 6% after 20 years [5]. After revision surgery, the dislocation rate levels at 5.4% in the first year after the operation [6]. Dislocation studies of THA have been performed based on component positioning, with an emphasis on cup orientation [7–10], the effect of artificial head size [5,11,12] and impingement as causes of a prosthesis head dislocation [13–15]. Still more than 50% of dislocations occur when the cup is in the so-called safe zone position [10]. One of the causative factors for instability after THA might be spino-pelvic imbalance [16], decreased mobility of the spine, decreased tilt of the pelvis that might cause impingement [17] and liner wearing [18]. According to latest review soft tissue insufficiency might be the cause for dislocations and not the approach used [19]. A larger femoral head diameter increases the range of motion before the prosthesis neck impinges on the acetabulum liner, which causes the prosthesis to dislocate [5,11,20]. Despite the careful positioning and selection of THA components, dislocations still occur. The question arises as to whether THA changes the geometry of the hip in such a way as to affect the biomechanical parameters in the joint, forcing the hip to dislocate at the edge of the motion range. The HIPSTRESS method was developed to calculate biomechanical parameters in the hip considering pelvis and femur anatomy [21,22]. Using this method, the hip stress distribution can be calculated in a neutral hip position during a one-legged stance, using a standard X-ray image of the hip and pelvis. It has been validated by clinical studies considering various pathologies in native hips [23,24] and in hips with total hip arthroplasties [25–27]. The HIPSTRESS method demonstrates that linear wear occurs in the direction of the stress pole [25,26] and that it is proportional to the peak stress on the weight bearing area [25]. Because of this effect, the volumetric wear on the cup is less for a larger abduction angle of the cup [27], since the head partly migrates out of the socket [27]. On the other hand, it has been shown that this could be unfavorable in terms of dislocation [27]. The aim of this work was to provide an answer to the question posed by the results of previous work [27]: whether arthroplasties that have suffered dislocation have a less favorable stress distribution. The hypothesis of this work was that biomechanical parameters (higher peak stress, more lateral stress pole and less negative stress gradient index) are predictors for dislocation of a THA. To test this hypothesis, we compared the biomechanical parameters of a population of THA that had suffered dislocation and a population of THA that were successful at least 10 years post-operatively. Methods The study was designed as a retrospective individual case control study, level of evidence 3B. It was approved by Slovene National Medical Ethics Committee letter No.: 110/04/15 which serves also as an institutional review board approval prior to performing the study. Since the study was retrograde and biomechanical analysis was done on the X-ray images that were coded and already taken before the beginning of the study no informed consent was needed. Anteroposterior (AP) X-ray images of the hip and pelvic skeleton of patients that had undergone THA were used to measure geometrical parameters relevant for a determination of biomechanical parameters within the HIPSTRESS method. X-ray images of patients that had suffered dislocation of hip arthroplasties were included in the study group. Patients were chosen from the emergency department database on the basis of a diagnosis of hip dislocation, ICD S73.0. Patients admitted to the Emergency Department, University Clinical Center Ljubljana from November 2012 until September 2015 were included. Images were downloaded from the Impax server and coded. Eighty-one patients with a diagnosis of dislocation of the PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 2 / 13 Hip stress arthroplasty dislocation predictor hip joint were gathered. Exclusion criteria were patients that had suffered hip dislocation due to high energy trauma (17 patients), patients with whom dislocation had occurred due to material breakage of the hip prosthesis (2 patients) and patients with whom the contours of the femur or pelvis were not clearly visible on the X-ray image (1 patient). X-ray images of the whole pelvis and hips after reduction of the dislocation were used for analysis. Images were taken in a supine position. The patients were awake when taking the image. After excluding all patients with the exclusion criteria, 61 patients remained in the study group. Forty-one of them were female and 20 male, and the average age was 64.4 years. There were 24 (39%) right hips and 37 (61%) left hips. Twenty-five (41%) of them had already undergone hip arthroplasty on the contralateral hip. The time from the operation to dislocation was on average 402,1 (SD 771,4) days. Dislocation occurred in 47 (77%) cases in less than one year after the THA procedure. The average time to dislocation in this group was 57,2 (SD 79,7) days. Dislocations occurred between 1 and 10 years in 14 (23%) cases after the THA procedure (average 4,27 years with SD 2.53 years). In the study group, the posterior approach was used in 9 patients, the anterolateral approach in 12 patients and the lateral approach in 40 patients. Patients with partial arthroplasty involving two artificial femoral heads (6 patients) were excluded from the study, since different biomechanics applies due to the double mobility of the partial arthroplasty joint [28]. Patients admitted with partial hip arthroplasties and three patients with THA (altogether 9 patients) were operated at the Clinical Department of Traumatology, University Medical Center Ljubljana. In these patients, the size of the femoral head could be retrieved from the archive. In the remaining 52 patients, the size of the femoral head was not known. Standard X-ray images of the hip and pelvis taken at the Emergency Department, University Medical Center Ljubljana were assumed to have an average magnification of 115% and the size of the prosthesis head was estimated by rounding to 28mm, 32mm or 36 mm using software developed for preoperative planning at the Department of Traumatology, University Medical Center Ljubljana. Twenty-six (47%) hips in the study group with THA had a femoral head diameter of 28 mm, 12 (22%) had a femoral head diameter of 32 mm and 17 (31%) had a femoral head diameter of 36 mm. On average, the radius of the prosthesis head was 15.67 mm ± 1.75 mm. In the study group, there were two cases where elevated liners were seen on the x ray pictures. The data on the inlay and the prosthesis head were available from the archive for three cases only. In these three cases we did not see any elevated liner. Stems were cemented in 26 cases and uncemented in 29 cases. None of the femoral stems were loosened. The acetabulum components were uncemented in 23 cases and cemented in 32 cases. There were signs of loosening of the cemented acetabulum component in one case. To define the control group, we examined X-ray images of 311 patients who had undergone total hip arthroplasty (THA) at the Orthopedic Hospital Valdoltra, Slovenia. The first available X-ray images or THA with whole pelvis (in terms of date) were taken from the Impax server at the hospital. Inclusion criteria were an X-ray image of the pelvis and proximal femora after implantation, no event of hip dislocation or septic or aseptic loosening and regular follow-up for at least 10 years. Patients who had undergone any revision procedure during that time were also excluded. Ninety-four hips (54 (63%) right and 35 (37%) left) of 77 patients that met the inclusion criteria (45 female and 32 male) were included in the analysis. Sixty-nine of them also had a prosthesis on the contralateral side. The average age of the patients included at the time of implantation was 59.6 years. There were 79 (84%) THA with a femoral head diameter of 28mm, 2 (2%) of them had a femoral head diameter of 32 mm and 13 (14%) had a femoral head diameter of 36mm. In the control group, acetabulum was cemented in 7 cases and uncemented in 87 cases. Inlay was ceramic–alumina in 20 cases and polyethylene in 60 cases (UHMWPE in 44 cases, crosslinked PE in 14 cases and Eduron PE in 2 cases). Head was PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 3 / 13 Hip stress arthroplasty dislocation predictor ceramic–alumina in 34 cases, CoCr alloy in 30 cases and Fe alloy in 30 cases. Femur stem was cemented in 5 cases and uncemented with diaphyseal fit in 89 cases. In the control group, lateral approach was used in all THA procedures. For biomechanical evaluation, three-dimensional mathematical models of an adult human hip within the HIPSTRESS method were used [22,24]. The models are described in detail elsewhere (see for example ref. [24]) so only a brief description will be given here. The method consists of two mathematical models: one for determination of the resultant hip force in the representative body position for everyday activities [29], i.e., the one-legged stance [30], and the other for determination of contact hip stress distribution [21]. The model for resultant hip force is based on force and torque equilibrium equations [22,30]. The model describes a system composed of two segments: the loaded leg and the rest of the body. It includes 9 effective muscle forces, the weight of the segments and the intersegment force (the resultant hip force). The reference muscle attachment points are obtained from measurements performed on a cadaver and then re-scaled for the individual hip considered. Since the X-ray image is two-dimensional, data in the third dimension are taken to be equal to the reference values. The model for force uses as input the geometrical parameters of pelvis and proximal femur: pelvic width (C) and height (H), inter-hip distance (l) and the position of the muscle attachment point on the greater trochanter (x,z) (Fig 1). Stress integrated over the load-bearing area yields the resultant hip force R = ʃ p dA, where p is stress and dA is the area element. The calculations and procedures have been explained previously [23–25,31]. HIPSTRESS models use hip and pelvis geometric parameters as input data: inter-hip distance (l), height of the pelvis (H), horizontal distance from the prosthesis head center to the lateral edge of the pelvis (C), position of the greater trochanter relative to the prosthesis head center in the coordinate system of the femur (distances z and x) and abduction angle. The geometrical parameters were determined using CorelDRAW Graphics Suite X7, 2015, Ottawa, Canada, by two blinded measurers. HIPSTRESS software [31] was used for calculation of the biomechanical parameters. (Fig 1) Previous studies [32–36] have indicated that the peak stress on the load-bearing area pmax is a useful biomechanical parameter. If the stress pole is located inside the load bearing area, pmax is equal to the value of the stress at the pole. If the stress pole lies outside the load-bearing area, contact stress is highest at the point of the load-bearing area that is closest to the pole (Eq 1), �p � Wabd Ypole ð1Þ pmax ¼ p0 cos 2 where p0 is the value of stress at its pole, ϑabd is the abduction angle of the prosthesis cup and Θpole is the angle of the stress pole (Fig 1). Another indicator of the stress distribution is the gradient of stress, represented by its value at the lateral rim of the cup Gp (Eq 2) [27,37], Gp ¼ p0 cosðp Wabd Ypole Þ=r ð2Þ where r is the radius of the articular surface. If the pole of stress distribution lies outside the load-bearing area (i.e., if Θpole > π/2 –ϑabd), then Gp is positive, stress attains its highest value at the lateral rim and falls off rapidly in the medial direction, while the corresponding weight bearing area is small [38]. Such a distribution represents dysplastic hips [38]. If, however, the pole of stress distribution lies inside the load–bearing area (if Θpole < π/2 –ϑabd), then stress reaches its peak within the weight bearing area, which is consequently larger and Gp is negative [38]. The functional angle of load bearing ϑf is defined as (Eq 3). Wf ¼ ðp PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 Wabd Ypole Þ ð3Þ 4 / 13 Hip stress arthroplasty dislocation predictor Fig 1. Geometric and biomechanical parameters within the HIPSTRESS models that are used for calculation of stress distribution in a right artificial hip. R resultant hip force; pmax peak stress on the load bearing area; θpole angle of the stress pole; ϑabd abduction angle; ϑR angle of the resultant hip force; C horizontal distance between the center of the prosthesis head and the most lateral point on the iliac crest; H vertical distance between the center of the prosthesis head and the highest point on the iliac crest; x vertical distance between the center of the prosthesis head and the point on the greater trochanter in the direction of the femur; z distance between the center of the prosthesis head and the point on the greater trochanter perpendicular to the femur axis; l distance between the centers of the femoral heads. https://doi.org/10.1371/journal.pone.0225459.g001 In relation to dislocation, high resultant hip force and high peak stress are unfavorable. However, a high gradient index and more laterally positioned pole are expected to represent an even greater risk of dislocation, since the head is pushed more laterally each time the leg is loaded. PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 5 / 13 Hip stress arthroplasty dislocation predictor The peak stress pmax is proportional to r-2, while the hip stress gradient index Gp is proportional to r-3 [21,38]. Since different sizes of prosthesis heads were involved, the effect of the femoral head size on biomechanical parameters was eliminated by multiplying pmax by r2 and Gp by r3. The resultant hip force, peak stress and stress gradient index are also proportional to body weight Wb. Since the body weight was unknown, its effect was eliminated by normalizing the respective parameters by Wb. The normalized biomechanical parameters R/WB, pmaxr2/ Wb, Gpr3/Wb, ϑf and Θpole express the geometry of the pelvis and the proximal femur and the geometry and position of the arthroplasty’s elements (but not the size of the artificial head). Statistical analysis of the biomechanical parameters between the two groups was done using the Student T—test. If the p value was � 0.05, the difference between these two groups was significant. The statistical power (1-β) of the result was taken as sufficient when the power was >80%. Statistical analysis was done using Microsoft Excel 2010 (14.0.7188.5000, Microsoft Corporation, Santa Rosa, California, USA). The power of the statistics was calculated using a statistics power calculator on the internet: http://clincalc.com/Stats/Power.aspx Results Normalized resultant hip force R/Wb and normalized peak stress pmax.r2/Wb were considerably and statistically significantly less favorable in the study group than in the control group, with sufficient statistical power. The position of the stress pole was more lateral (less favorable) in the study group. The difference was statistically significant but with somewhat deficient statistical power (Table 1). The normalized stress gradient index Gp.r3/Wb and functional angle of load bearing showed no statistically significant difference, although it was less negative and smaller (which is unfavorable) in the study group. There was a considerable and statistically significant difference in parameters x (distance between the center of the prosthesis head and the point on the greater trochanter in the direction of the femur axis) and C (horizontal distance between the center of the prosthesis head and the most lateral point of the iliac crest) between the study and control groups (Table 2). Higher x and C indicate less favorable biomechanical parameters in the study group. The difference between the abduction angles in the study group and control group was minute, which explains the lack of statistical significance of the difference in the functional angle of weight bearing (Table 1). Table 1. Comparison of biomechanical parameters of the hips with THA in the study and control group. Average ± SD Study group (55 THA) Control group (94 THA) Difference (%) p Power (1-β) R/Wb mean 2.71 (SD 0.36)� mean 2.54 (SD 0.32) 6.3 0.004 89.9% pmax x r2/Wb mean 152.11 (SD 37.04)� mean 135.32 (SD 21.42) 11.0 0.001 92.7% Gp x r3/Wb mean -828287.70 (SD 413381.01)� mean -871926.04 (SD 220240.41) -5.27 0.400 10.9% ϑf (˚) mean 129.13 (SD 17.57) mean 132.90 (SD 13.60) -2.9 0.146 39.5% θpole (˚) mean 5.77 (SD 9.71)� mean 2.86 (SD6.08) 50.0 0.026 62.9% R/Wb, resultant hip force normalized by body weight; pmax x r2/Wb; effect of pelvis geometry on peak stress on the load bearing area normalized by body weight; Gp x r3/ Wb; effect of pelvic geometry on the peak hip gradient index; ϑf (˚), functional angle of the load bearing; θpole (˚), position of the stress pole. (� ) An asterisk denotes a value with higher risk for dislocation https://doi.org/10.1371/journal.pone.0225459.t001 PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 6 / 13 Hip stress arthroplasty dislocation predictor Table 2. Comparison of geometrical parameters of the hips with THA in the study group and control group. Average ± SD Study group (55 THA) Control group (94 THA) Difference (%) p Power (1-β) H (mm) mean 136.80 (SD 13.53) mean 133.78 (SD11.18) 2.2 0.144 40.6% z (mm) mean 56.73 (SD 8.71) mean 59.18 (SD 6.73) -4.3 0.057 56.3% x (mm) mean 14.77 (SD 8.69)� mean 7.81 (SD 5.34) 47.1 0.000 100% C (mm) mean 59.58 (SD 8.87)� mean 55.52 (SD 9.22) 6.8 0.010 84.8% l (mm) mean 179.61 (SD 11.15) mean 177.13 (SD 10.26) 1.38 0.169 10.9% ϑabd (˚) mean 45.10 (SD9.12) mean 44.24 (SD 7.97) 1.9 0.547 14.5% H (mm), vertical distance between the center of the prosthesis head and the highest point on the iliac crest; z (mm), distance between the center of the prosthesis head and the point on the greater trochanter perpendicular to the femur axis; x (mm), vertical distance between the center of the prosthesis head and the point on the greater trochanter in the direction of the femur; C (mm), horizontal distance between the center of the prosthesis head and the most lateral point on the iliac crest; l (mm), horizontal distance between the right and left center of the femoral head; ϑabd (˚), abduction angle. (� ) An asterisk denotes a value with a higher risk of dislocation. https://doi.org/10.1371/journal.pone.0225459.t002 To evaluate whether there were any significant differences in the geometry of the pelvis and hip biomechanics between the study and control groups, a comparison of the native hips contralateral to the arthroplasties between the study and control groups was performed. Since there were cases in both groups with bilateral arthroplasties, only subjects without contralateral hip arthroplasty were taken for comparison. There were no statistically significant differences between hips contralateral to arthroplasties that had suffered dislocation and arthroplasties that were functional at least 10 years postoperatively (Tables 3 and 4). This indicates that the geometry of the pelvis and proximal femur of the patient before arthroplasty is not the cause of the difference between the study and control groups and that changes induced by arthroplasty surgery are connected to the difference in the biomechanical parameters of the study and control groups. Discussion Our study supports the hypothesis that contact stress distribution on the prosthesis head is a predictor of arthroplasty dislocation. The hypothesis of this study was formed following previous work by Rijavec et al. [27], in which the effect of cup inclination on predicted contact stress-induced volumetric wear in THA was considered. In that study, it was indicated that a larger abduction angle of the prosthesis cup is more favorable in terms of prosthesis wear, although it can represent a larger risk of its dislocation. It is shown above (Table 1) that THA that had suffered dislocation had a less favorable distribution of contact stress (given by its peak value and the position of the pole), which pushed the artificial head more laterally than in the case of prostheses that were functional at least 10 years post-operatively. A previous study had shown that the head migrates in the direction of the stress pole [25]. This process changes the shape of the interface between the head and the cup and contributes to the development of a lever that leads to dislocation. Comparison of native hips contralateral to dislocated and functional arthroplasties showed no statistically significant differences, in either biomechanical parameters or geometrical parameters (Tables 3 and 4), indicating that the initial geometry of the pelvis and proximal femur was on average the same in the two groups. It is the change in pelvic anatomy after the PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 7 / 13 Hip stress arthroplasty dislocation predictor Table 3. Comparison of biomechanical parameters of native hips contralateral to arthroplasties in the study and control group. Average ± SD Native hips contralateral to arthroplasties in the study group (36 hips) Native hips contralateral to arthroplasties in the control group (25 hips) Difference (%) p Power (1β) R/Wb mean 2.71 (SD 0.89) mean 2.66 (SD 0.42) 1.76 0.780 8.8% pmax x r2/Wb mean 168.77 (SD 65.97) mean 183.27 (SD 87.25) 8.59 0.485 17.3% Gp x r3/Wb mean -480308.69 (SD 730010.97) mean -561387.71 (SD 341552.74) 14.44 0.605 14.4% ϑf (˚) mean 113.69 (SD 15.86) mean 113.43 (SD1 9.16) 0.23 0.955 5.1% θpole (˚) mean 11.16 (SD7.44) mean 12.50 (SD 11.06) 11.96 0.601 13.2% R/Wb, resultant hip force normalized by body weight; pmax x r2/Wb; effect of pelvis geometry on peak stress on the load bearing area normalized by body weight; Gp x r3/ Wb; effect of pelvic geometry on the peak hip gradient index; ϑf (˚), functional angle of the load bearing; θpole (˚), position of the stress pole. https://doi.org/10.1371/journal.pone.0225459.t003 arthroplasty procedure that changes the biomechanics of the hip and these changes were less favorable in the group of prostheses that had suffered dislocation. Dislocation of the hip joint after THA is one of the major side complications (2% - 4% after primary total hip arthroplasty) [2,39] and its causes have been studied previously [5,7–20,39– 42]. Among patient related factors, the presence of neuromuscular conditions, such as cerebral palsy, muscle dystrophy, dementia and Parkinson’s disease, is one of the main risk factors [39,43]. More dislocations were found with patients older than 80 years [43], patients with a femoral neck fracture as the primary diagnosis [40,42] and patients with an ASA (American Society of Anesthesiologists) score of 3 or 4 [40]. Among procedure related factors, the measured parameters of component positions, a cup inclination out of the range of 40˚ ± 10˚, a Table 4. Comparison of geometrical parameters of native hips contralateral to arthroplasties in the study and control group. Average ± SD Native hips contralateral to arthroplasties in the study group (36 hips) Native hips contralateral to arthroplasties in the control group (25 hips) Difference (%) P Power (1β) H (mm) mean 139.19 (SD 10.65) mean 142.05 (SD 13.89) 2.06 0.389 21.8% z (mm) mean 60.25 (SD 5.62) mean 58.24 (SD 7.93) 3.34 0.279 29% x (mm) mean 6.33 (SD 5.09) mean 7.61 (SD 4.81) 20.17 0.324 25.9% C (mm) mean 52.88 (SD 9.83) mean 56.61 (SD 10.42) 7.07 0.164 40.6% x (mm) mean 6.33 (SD 5.09) mean 7.61 (SD 4.81) 20.17 0.324 25.9% l(mm) mean 181.28 (SD 14.07) mean 177.74 (SD 10.13) 2 0.279 20.7% ϑabd(˚) mean 55.15 (SD8.92) mean 54.07 (SD 9.70) -3.08 0.662 11.4% H (mm), vertical distance between the center of the prosthesis head and the highest point on the iliac crest; z (mm), distance between the center of the prosthesis head and the point on the greater trochanter perpendicular to the femur axis; x (mm), vertical distance between the center of the prosthesis head and the point on the greater trochanter in the direction of the femur; C (mm), horizontal distance between the center of the prosthesis head and the most lateral point on the iliac crest; l (mm), horizontal distance between the right and left center of the femoral head; ϑabd (˚), abduction angle. https://doi.org/10.1371/journal.pone.0225459.t004 PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 8 / 13 Hip stress arthroplasty dislocation predictor cup anteversion of less than 10˚ or more than 35˚, a stem anteversion out of the range of 14.8˚ ± 6,01˚ and a height of hip rotation center outside the range of 2.16 mm ± 9.11 mm, increased the risk of dislocation [8,9,40]. The artificial head size, leg length discrepancy and acetabular inclination were all studied in two separate studies and it was found that these are not statistically important factors predicting dislocation of the femoral head [7,44]. On the other hand, in a study by Berry [5], a smaller size of the prosthesis head was shown to be related to a higher dislocation rate of THA. In a study by Forde et al. [7], it was reported that if the femoral offset was at least 3 mm greater than on the contralateral side, the risk of dislocation was lower [7]. Offset is expressed in the HIPSTRESS model by parameter z. A larger z is biomechanically favorable, since it implies a lower resultant force and larger angle of inclination, which consequently means lower peak stress, a more medial location of the pole, a smaller gradient index and a larger functional angle of weight bearing[24]. Our results are therefore in agreement. In a study by Rijavec [27] that considered the effect of cup inclination on predicted contact stress-induced volumetric wear in THA, stress distribution was proposed as a relevant factor connected to the probability of dislocation of the artificial head. Our results show that normalized stress was indeed considerably and statistically significantly less favorable in the study group. The position of the pole was statistically significantly less favorable in the study group, while the difference in gradient index Gp.r3/Wb, albeit showing a less favorable configuration in the study group, was not statistically significant. Since three of the parameters were on average less favorable in the study group, our results support the proposed hypothesis. The most frequently considered measurements in prostheses are abduction angle and the lateral offset [7,44]. We found on average no statistically significant differences between abduction angles in the study and control groups, although the standard deviation was somewhat larger in the study group. The average values of the abduction angle were close to ideal (45 degrees) in both groups, so the differences in biomechanical parameters could not have been due to the abduction angle, which was also found in a study by Forde[7]. On the other hand, the offset is connected to the shape of the greater trochanter. We found that there was a considerable and statistically significant difference in the position of the characteristic point on the greater trochanter, which was less favorable in hips that had suffered dislocation. Our study and control groups had a different distribution of artificial head sizes and we focused on the effect of the geometry of the pelvis and the proximal femur and the inclination of the artificial cup. We therefore chose biomechanical parameters that were independent of the artificial head size. The effect of femoral head size was considered [45], who reported that a larger head diminishes the probability of impingement between the femoral neck and acetabular liner. Our analysis focused on the one-legged stance and did not consider events connected specifically to other body positions that could predispose the femoral head to dislocate. Preoperative planning is advised before implantation of an artificial hip and is usually done [46]. Optimization of the choice and position of prosthesis elements using simulation with a mathematical model could be included in preoperative planning. Simulation of postoperative biomechanical parameters would be useful in planning the configuration of prostheses, especially in demographic groups in which hips are more vulnerable to dislocation, or in revision cases. In cases in which preoperative planning predicted an arthroplasty prone to dislocation, the surgeon could decide on another implant configuration. The main limitation of the study is that biomechanical parameters are determined using mathematical 3D model on the two dimensional AP image of the pelvis and proximal femora. From this image spinopelvic alignment and anteversion of the cup cannot be accessed. In the recent studies [16,17] spinopelvic alignment was suggested as an important factor that could predispose late dislocation of the total hip endoprosthesis. PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 9 / 13 Hip stress arthroplasty dislocation predictor Other limitation is that the control X-rays of the pelvis and proximal femora after the dislocation were taken in a supine and not in a standing position. Conclusions Our results showed that the shape of the pelvis and proximal femur after total hip arthroplasty impacted on a less favorable stress distribution in the representative everyday activity, the onelegged stance, in prostheses that had suffered dislocation. Although the hip does not dislocate during the one-legged stance, these hips had higher stress, accumulated more laterally, than arthroplasties that were functional for at least 10 years. The more lateral position of the stress pole could remodel the joint and predispose dislocation during other activities. Supporting information S1 File. Microsoft Office Excel file with measurements and calculations of all the values. (XLSX) Acknowledgments The authors thank Martin Cregeen for language editing the paper. Author Contributions Conceptualization: Matevž Tomaževič, Urban Kurent, Matej Cimerman, Veronika KraljIglič. Data curation: Matevž Tomaževič, Tina Kaiba, Urban Kurent, Rihard Trebše, Veronika KraljIglič. Formal analysis: Matevž Tomaževič, Tina Kaiba, Urban Kurent. Funding acquisition: Veronika Kralj-Iglič. Investigation: Matevž Tomaževič, Urban Kurent, Veronika Kralj-Iglič. Methodology: Matevž Tomaževič, Matej Cimerman, Veronika Kralj-Iglič. Project administration: Veronika Kralj-Iglič. Resources: Veronika Kralj-Iglič. Software: Veronika Kralj-Iglič. Supervision: Rihard Trebše, Matej Cimerman, Veronika Kralj-Iglič. Validation: Matevž Tomaževič, Tina Kaiba, Rihard Trebše, Veronika Kralj-Iglič. Visualization: Matevž Tomaževič, Veronika Kralj-Iglič. Writing – original draft: Matevž Tomaževič, Urban Kurent. Writing – review & editing: Matevž Tomaževič, Rihard Trebše, Matej Cimerman, Veronika Kralj-Iglič. References 1. Finalised Patient Reported Outcome Measures (PROMs) in England for Hip and Knee Replacement Procedures (April 2017 to March 2018). In: NHS Digital [Internet]. [cited 16 Feb 2019]. Available: https:// digital.nhs.uk/data-and-information/publications/statistical/patient-reported-outcome-measures-proms/ hip-and-knee-replacement-procedures—april-2017-to-march-2018 PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 10 / 13 Hip stress arthroplasty dislocation predictor 2. Ferguson RJ, Palmer AJ, Taylor A, Porter ML, Malchau H, Glyn-Jones S. Hip replacement. The Lancet. 2018; 392: 1662–1671. https://doi.org/10.1016/S0140-6736(18)31777-X 3. Annual reports from The Swedish Hip Arthroplasty Register � Svenska höftprotesregistret. [cited 17 Jun 2018]. Available: https://shpr.registercentrum.se/shar-in-english/annual-reports-from-the-swedish-hiparthroplasty-register/p/rkeyyeElz 4. Goel A, Lau EC, Ong KL, Berry DJ, Malkani AL. Dislocation Rates Following Primary Total Hip Arthroplasty Have Plateaued in the Medicare Population. J Arthroplasty. 2015; 30: 743–746. https://doi.org/ 10.1016/j.arth.2014.11.012 PMID: 25573179 5. Berry DJ. Effect of Femoral Head Diameter and Operative Approach on Risk of Dislocation After Primary Total Hip Arthroplasty. J Bone Jt Surg Am. 2005; 87: 2456. https://doi.org/10.2106/JBJS.D.02860 PMID: 16264121 6. Badarudeen S, Shu AC, Ong KL, Baykal D, Lau EC, Malkani AL. Complications After Revision Total Hip Arthroplasty in the Medicare Population. J Arthroplasty. 2017; 32: 1954–1958. https://doi.org/10.1016/j. arth.2017.01.037 PMID: 28236550 7. Forde B, Engeln K, Bedair H, Bene N, Talmo C, Nandi S. Restoring femoral offset is the most important technical factor in preventing total hip arthroplasty dislocation. J Orthop. 2018; 15: 131–133. https://doi. org/10.1016/j.jor.2018.01.026 PMID: 29657456 8. Lewinnek GE, Lewis JL, Tarr R, Compere CL, Zimmerman JR. Dislocations after total hip-replacement arthroplasties. J Bone Jt Surg. 1978; 60: 217–220. 9. Yoon Y-S, Hodgson AJ, Tonetti J, Masri BA, Duncan CP. Resolving inconsistencies in defining the target orientation for the acetabular cup angles in total hip arthroplasty. Clin Biomech. 2008; 23: 253–259. https://doi.org/10.1016/j.clinbiomech.2007.10.014 PMID: 18069102 10. Abdel MP, von Roth P, Jennings MT, Hanssen AD, Pagnano MW. What Safe Zone? The Vast Majority of Dislocated THAs Are Within the Lewinnek Safe Zone for Acetabular Component Position. Clin Orthop. 2016; 474: 386–391. https://doi.org/10.1007/s11999-015-4432-5 PMID: 26150264 11. Kluess D, Martin H, Mittelmeier W, Schimtz K-P, Bader R. Influence of femoral head size on impingement, dislocation and stress distribution in total hip replacement. Med Eng Phys. 2007; 29: 465–471. https://doi.org/10.1016/j.medengphy.2006.07.001 PMID: 16901743 12. Bunn A, Colwell CW, D’Lima DD. Effect of head diameter on passive and active dynamic hip dislocation. J Orthop Res. 2014; 32: 1525–1531. https://doi.org/10.1002/jor.22659 PMID: 24961686 13. Nadzadi ME, Pedersen DR, Yack HJ, Callaghan JJ, Brown TD. Kinematics, kinetics, and finite element analysis of commonplace maneuvers at risk for total hip dislocation. J Biomech. 2003; 36: 577–591. https://doi.org/10.1016/s0021-9290(02)00232-4 PMID: 12600348 14. Elkins JM, Kruger KM, Pedersen DR, Callaghan JJ, Brown TD. Edge-Loading Severity as a Function of Cup Lip Radius in Metal-on-Metal Total Hips–A Finite Element Analysis. J Orthop Res Off Publ Orthop Res Soc. 2012; 30: 169–177. https://doi.org/10.1002/jor.21524 PMID: 21812025 15. Scifert CF, Brown TD, Lipman JD. Finite element analysis of a novel design approach to resisting total hip dislocation. Clin Biomech. 1999; 14: 697–703. https://doi.org/10.1016/S0268-0033(99)00054-6 16. Heckmann N, McKnight B, Stefl M, Trasolini N, Ike H, Dorr L. Late Dislocation Following Total Hip Arthroplasty: Spinopelvic Imbalance as a Causative Factor. J Bone Jt Surg. 2018; 100: 1845–1853. https://doi.org/10.2106/JBJS.18.00078 PMID: 30399079 17. Ike H, Dorr L, Trasolini N, Stefl M, McKnight B, Heckmann N. Spine-Pelvis-Hip Relationship in the Functioning of a Total Hip Replacement. J Bone Jt Surg. 2018; 100: 1606–1615. https://doi.org/10.2106/ JBJS.17.00403 PMID: 30234627 18. Parvizi J, Wade F, Rapuri V, Springer B, Berry D, Hozack W. Revision Hip Arthroplasty for Late Instability Secondary to Polyethylene Wear. Clin Orthop. 2006; 447: 66–69. https://doi.org/10.1097/01.blo. 0000218751.14989.a6 PMID: 16672896 19. Rowan FE, Benjamin B, Pietrak JR, Haddad FS. Prevention of Dislocation After Total Hip Arthroplasty. J Arthroplasty. 2018; 33: 1316–1324. https://doi.org/10.1016/j.arth.2018.01.047 PMID: 29525344 20. Tanino H, Harman MK, Banks SA, Hodge WA. Association between dislocation, impingement, and articular geometry in retrieved acetabular polyethylene cups. J Orthop Res. 2007; 25: 1401–1407. https://doi.org/10.1002/jor.20410 PMID: 17471491 21. Ipavec M, Brand RA, Pedersen DR, Mavčič B, Kralj-Iglič V, Iglič A. Mathematical modelling of stress in the hip during gait. J Biomech. 1999; 32: 1229–1235. https://doi.org/10.1016/s0021-9290(99)00119-0 PMID: 10541074 22. Iglič A, Srakar F, Antolic V. Influence of the pelvic shape on the biomechanical status of the hip. Clin Biomech. 1993; 8: 223–224. https://doi.org/10.1016/0268-0033(93)90019-E 23. Kralj-Iglič V, Dolinar D, Ivanovski M, List I, Daniel M. Role of Biomechanical Parameters in Hip Osteoarthritis and Avascular Necrosis of Femoral Head. In: Naik GR, editor. Applied Biological Engineering— PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 11 / 13 Hip stress arthroplasty dislocation predictor Principles and Practice. InTech; 2012. Available: http://www.intechopen.com/books/applied-biologicalengineering-principles-and-practice/role-of-biomechanical-parameters-in-hip-osteoarthritis-andavascular-necrosis-of-femoral-head24. Kralj-Iglič V. Validation of Mechanical Hypothesis of hip Arthritis Development by HIPSTRESS Method. In: Chen Q, editor. Osteoarthritis—Progress in Basic Research and Treatment. InTech; 2015. Available: http://www.intechopen.com/books/osteoarthritis-progress-in-basic-research-and-treatment/ validation-of-mechanical-hypothesis-of-hip-arthritis-development-by-hipstress-method 25. Košak R, Kralj-Iglič V, Iglič A, Daniel M. Polyethylene wear is related to patient-specific contact stress in THA. Clin Orthop. 2011; 469: 3415–3422. https://doi.org/10.1007/s11999-011-2078-5 PMID: 21948311 26. Košak R, Antolič V, Pavlovčič V, Kralj-Iglič V, Milošev I, Vidmar G, et al. Polyethylene wear in total hip prostheses: the influence of direction of linear wear on volumetric wear determined from radiographic data. Skeletal Radiol. 2003; 32: 679–686. https://doi.org/10.1007/s00256-003-0685-2 PMID: 13680199 27. Rijavec B, Košak R, Daniel M, Kralj-IgliČ V, Dolinar D. Effect of cup inclination on predicted contact stress-induced volumetric wear in total hip replacement. Comput Methods Biomech Biomed Engin. 2015; 18: 1468–1473. https://doi.org/10.1080/10255842.2014.916700 PMID: 24830356 28. Krein SW, Chao EYS. Biomechanics of bipolar hip endoprostheses. J Orthop Res. 1984; 2: 356–368. https://doi.org/10.1002/jor.1100020408 PMID: 6527161 29. Debevec H, Pedersen DR, Iglicč A, Daniel M. One-Legged Stance as a Representative Static Body Position for Calculation of Hip Contact Stress Distribution in Clinical Studies. J Appl Biomech. 2010; 26: 522–525. https://doi.org/10.1123/jab.26.4.522 PMID: 21245514 30. Iglič A, Srakar F, Antolič V, Kralj-Iglič V, Batagelj V. Mathematical analysis of Chiari osteotomy. Acta Orthop Iugosl. 1990; 20: 35–39. 31. Iglič A, Kralj-Iglič V, Daniel M, Maček-Lebar A. Computer Determination of Contact Stress Distribution and Size of Weight Bearing Area in the Human Hip Joint. Comput Methods Biomech Biomed Engin. 2002; 5: 185–192. https://doi.org/10.1080/10255840290010300 PMID: 12186728 32. Mavčič B, Pompe B, Antolič V, Daniel M, Iglič A, Kralj-Iglič V. Mathematical estimation of stress distribution in normal and dysplastic human hips. J Orthop Res. 2002; 20: 1025–1030. https://doi.org/10.1016/ S0736-0266(02)00014-1 PMID: 12382969 33. Mavčič B, Iglič A, Kralj-Iglič V, Brand RA, Vengust R. Cumulative Hip Contact Stress Predicts Osteoarthritis in DDH. Clin Orthop. 2008; 466: 884–891. https://doi.org/10.1007/s11999-008-0145-3 PMID: 18288549 34. Kralj M, Mavčič B, Antolič V, Iglič A, Kralj-Iglič V. The Bernese periacetabular osteotomy: clinical, radiographic and mechanical 7–15-year follow-up of 26 hips. Acta Orthop. 2005; 76: 833–840. https://doi. org/10.1080/17453670510045453 PMID: 16470438 35. Recnik G, Kralj-Iglič V, Iglič A, Antolič V, Kramberger S, Vengust R. Higher peak contact hip stress predetermines the side of hip involved in idiopathic osteoarthritis. Clin Biomech. 2007; 22: 1119–1124. https://doi.org/10.1016/j.clinbiomech.2007.08.002 PMID: 17868960 36. Recnik G, Vengust R, Kralj-Iglič V, Vogrin M, Krajnc Z, Kramberger S. Association between Sub-Clinical Acetabular Dysplasia and a Younger Age at Hip Arthroplasty in Idiopathic Osteoarthritis. J Int Med Res. 2009 [cited 10 Mar 2017]. https://doi.org/10.1177/147323000903700541 PMID: 19930871 37. Pompe B, Daniel M, Sochor M, Vengust R, Kralj-Iglic V, Iglic A. Gradient of contact stress in normal and dysplastic human hips. Med Eng Phys. 2003; 25: 379–385. https://doi.org/10.1016/s1350-4533(03) 00014-6 PMID: 12711235 38. Pompe B, Antolic V, Iglic A, Jaklic A, Krajl-Iglic V, Mavcic B. How should dysplastic human hips be evaluated? Cell Mol Biol Lett. 2002; 7: 144–146. PMID: 11944071 39. Dargel J, Oppermann J, Brüggemann G-P, Eysel P. Dislocation Following Total Hip Replacement. Dtsch Ärztebl Int. 2014; 111: 884–890. https://doi.org/10.3238/arztebl.2014.0884 PMID: 25597367 40. Kim Y-H, Choi Y, Kim J-S. Influence of Patient-, Design-, and Surgery-Related Factors on Rate of Dislocation After Primary Cementless Total Hip Arthroplasty. J Arthroplasty. 2009; 24: 1258–1263. https:// doi.org/10.1016/j.arth.2009.03.017 PMID: 19896063 41. Sikes CV, Lai LP, Schreiber M, Mont MA, Jinnah RH, Seyler TM. Instability After Total Hip Arthroplasty. J Arthroplasty. 2008; 23: 59–63. https://doi.org/10.1016/j.arth.2008.06.032 PMID: 18922375 42. Soong M, Rubash HE, Macaulay W. Dislocation After Total Hip Arthroplasty. J Am Acad Orthop Surg. 2004; 12: 314–321. https://doi.org/10.5435/00124635-200409000-00006 PMID: 15469226 43. Moriarity A, Ellanti P, Talha S, McKenna J. Dislocation and dissociation of bipolar hip hemiarthroplasty. BMJ Case Rep. 2015; bcr2015210282. https://doi.org/10.1136/bcr-2015-210282 PMID: 26178002 44. Brennan MSA, Khan F, Kiernan C, Queally JM, McQuillan J, Gormley IC, et al. Dislocation of Primary Total Hip Arthroplasty and the Risk of Redislocation: HIP Int. 2018 [cited 23 Apr 2018]. https://doi.org/ 10.5301/HIP.2012.9747 PMID: 23100149 PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 12 / 13 Hip stress arthroplasty dislocation predictor 45. Brown TD, Elkins JM, Pedersen DR, Callaghan JJ. Impingement and Dislocation in Total HIP Arthroplasty: Mechanisms and Consequences. Iowa Orthop J. 2014; 34: 1. PMID: 25328453 46. Eggli S, Pisan M, Müller ME. The value of preoperative planning for total hip arthroplasty. J Bone Joint Surg Br. 1998; 80: 382–390. https://doi.org/10.1302/0301-620x.80b3.7764 PMID: 9619923 PLOS ONE | https://doi.org/10.1371/journal.pone.0225459 November 20, 2019 13 / 13