An integrated benefit-risk assessment of cobalt-containing alloys used in medical devices: Implications for regulatory requirements in the European Union.

In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices. Assessments were performed on relevant preclinical and clinical carcinogenicity and reproductive toxicity data for Co and CoCA to meet the requirements under the EU Medical Device Regulation triggered by the ECHA re-classification (adopted in October 2019 under the 14th Adaptation to Technical Progress to CLP) and to address their relevance to patient safety. The objective of this review is to present an integrated overview of these assessments, a benefit-risk assessment and an examination of potential alternative materials. The data support the conclusion that the exposure to CoCA in medical devices via clinically relevant routes does not represent a hazard for carcinogenicity or reproductive toxicity. Additionally, the risk for the adverse effects that are known to occur with elevated Co concentrations (e.g., cardiomyopathy) are very low for CoCA implant devices (infrequent reports often reflecting a unique catastrophic failure event out of millions of patients) and negligible for CoCA non-implant devices (not measurable/no case reports). In conclusion, the favorable benefit-risk profile also in relation to possible alternatives presented herein strongly support continued use of CoCA in medical devices.

Range of Motion to Impingement Curves Create a New Patient-Specific Impingement-Free Zone for Acetabular Cup Placement.

INTRODUCTION: The acetabular "safe zone" has recently been questioned as a reliable reference for predicting total hip arthroplasty impingement and instability as many dislocations occur within the described parameters. Recently, an improved understanding of spino-pelvic mechanics has provided surgeons useful information to both identify those at a higher risk of dislocation and, in some cases, allows altering component positioning to accommodate the patient's individual "functional" range of motion. The purpose of this study was to create a new patient-specific impingement-free zone by considering range of motion (ROM) to prosthetic impingement for both high flexion and extension poses, thus demarcating a zone that avoids both anterior and posterior impingement, thereby creating an objective approach to identifying a patient's ideal functional safe zone. MATERIALS AND METHODS: A validated hip ROM three-dimensional simulator was utilized to create ROM-to-impingement curves for both high flexion as well as pivot and turn poses. The user imported a computerized tomography (CT) with a supine pelvic tilt (PT) value of zero and implant models (tapered wedge stem, 132° neck angle, 15° stem version, 36mm femoral head). Femur-to-pelvis relative motions were determined for three upright seated poses (femur flexed at 90° and 40° internal rotation, with 0°, 10°, and 20° posterior PT), one chair rise pose (femur flexed at 90° and 0° internal rotation, with the pelvis flexed anteriorly until the pelvis made contact with the femur), and three standing pivot and turn poses (femur set at 5° extension, and 35° external rotation, with 5° posterior PT, 0°, and 5° anterior PT). ROM-to-impingement curves for cup inclination versus anteversion were graphed and compared against the Lewinnek safe zone. RESULTS: The ROM-to-impingement curves provide an objective assessment of potential impingement sites as they relate to femoral rotation and pelvic tilt. The area between the stand and sit curves is the impingement-free area. A sitting erect pose with a simulated stiff spine (0° PT) yielded less impingement-free combinations of cup inclination and version than poses with greater than 0° posterior pelvic tilt. CONCLUSION: The results demonstrate that the acetabular target zone has a relatively small margin for error between the sitting and standing ROM curves to impingement. Importantly, anterior and posterior pelvic tilt can markedly increase the risk of impingement, potentially leading to posterior or anterior dislocations, respectively. This study highlights the importance of correctly identifying the patient-specific functional range of motion to execute optimal component positioning.

Effects of corrosion and cleaning method on taper dimensions: an in vitro investigation.

PURPOSE: Taper corrosion related revisions have recently been reported in the orthopaedic literature. Cleaning procedure of the trunnions during hip revision is not standardised. The purpose of this bench top investigation was to understand the alterations in the trunnion dimensions and surface roughness characteristics as a result of corrosion product build-up. METHODS: 8 titanium alloy trunnions and CoCr femoral heads assemblies were cyclically tested in a mechanical simulator. Following disassembly of the tested constructs, the trunnions were cleaned using 2 methods. The trunnion dimensions were measured using coordinate measuring machine, and surface roughness was measured using white light interferometry. The trunnions were reassembled with ceramic femoral heads and titanium sleeves following cleaning. Head/sleeve pull-off testing was conducted to understand the effects of cleaning methods on the pull-off strength. RESULTS: Grade 4 corrosion was observed on all trunnions after mechanical testing. The aggressive cleaning methods had a larger impact on the surface roughness when compared to the light cleaning method. The aggressive cleaning method also decreased the taper cone angle. The pull-off strength was not affected by the cleaning method and the pull-off values were approximately 50% of the assembly loads. CONCLUSIONS: The study suggests that trunnion cleaning method may alter the surface roughness and taper cone angle of the existing trunnion. However, the effects of these changes on the pull-off strength did not reach statistical significance. Complex corrosion testing under cyclic loading conditions are warranted to understand the long-term effects of these changes.

Effect of the support systems' compliance on total hip modular taper seating stability.

Assembly of a femoral head onto the stem remains non-standardized. The literature shows altering mechanical conditions during seating affects taper strength and lower assembly load may increase fretting corrosion during cyclic tests. This suggests overall performance may be affected by head assembly method. The purpose of this test was to perform bench-top studies to determine influence of peak force magnitude, load rate, and compliance of the system's support structure on initial stability of the taper. Custom manufactured CoCrMo femoral heads and Ti-6Al-4V taper analog samples were assembled with varying peak force magnitudes (2-10.1 kN), load rates (quasi-static vs impaction), and system compliance (rigid vs compliant). A clinically-relevant system compliance design was based off of force data collected during a cadaver impaction study. Tensile loads were then applied to disassemble the taper and quantify initial taper stability. Results indicated that taper stability (assessed by disassembly forces) increased linearly with assembly force and load rate did not have a significant effect on taper stability. When considering system compliance, a 42%-50% larger input energy, dependent on assembly force, was required in the compliant group to achieve a comparable impaction force to the rigid group. Even when this impaction force was achieved, the correlation between the coefficient, defined as distraction force divided by assembly load, was significantly reduced for the compliant test group. The compliant setup was intended to simulate a surgical scenario where patient and surgical factors may influence the resulting compliance. Based on results, surgical procedure and patient variables may have a significant effect on initial taper stability.

The Effect of Pelvic Tilt and Femoral Head Size on Hip Range-of-Motion to Impingement.

BACKGROUND: About 50%-70% of dislocators have cups placed within so-called "safe zones." It has been postulated that factors such as femoral head size and pelvic tilt, obliquity, or rotation may influence postoperative stability. Therefore, we assessed varying degrees of pelvic tilt and head sizes on the range of motion (ROM) to impingement. METHODS: A hip simulator was used to import models of 10 subjects who performed object pickup, squatting, and low-chair rising. Parameters were set for pelvic tilt, stem version, and the specific motions as defined by the subjects. Femur-to-pelvis relative motions were determined for abduction/adduction, internal/external rotation, and flexion/extension. Varying tilt angles were tested. Thirty-two millimeter and 36-mm head with a standard cup and 42-mm dual mobility cup were tested. Cup orientations for abduction and anteversion combinations were chosen, and computations of minimum clearances or impingement between components were made. RESULTS: The ROM to impingement varied with the different pelvic tilts and femoral head sizes and with the different motions. The larger the head size, the larger the impingement-free ROM. Negative 10° of pelvic tilt led to the largest impingement-free zone, whereas 10° of forward tilt was associated with fewer impingement-free cup anteversion and abduction angle combinations. Variations in pelvic tilt had the greatest influence on object pickup and affected the impingement-free "safe zone." CONCLUSION: Targets for impingement-free motion may be smaller when considering varying pelvic tilts and femoral head sizes, particularly for certain activities, such as object pickup. These findings may indicate the need for more individualized patient planning.

Acetabular Cup Anteversion and Inclination in Hip Range of Motion to Impingement.

BACKGROUND: It is advocated that to avoid complications associated with femoral stem impingement, acetabular positioning should be within a "safe zone." However, instability remains prevalent despite accurate cup positioning, with studies showing dislocations of cups despite positioning within safe zones. We assessed cup position angles associated with impingement in a group of subjects during (1) squatting; (2) object pick-up; and (3) low chair rise. METHODS: Ten subjects (mean age, 69 years; body mass index, 28.4 kg/m(2)) performed object pick up, squatting, and low-chair rising. Femur-to-pelvis relative motions were recorded for flexion/extension, abduction/adduction, and internal/external rotation. A previously reported custom-validated hip range-of-motion 3-dimensional simulator was used, set for neutral pelvic tilt and 15(°) of stem version. Acetabular cup abduction and anteversion combinations were chosen. The software computed minimum clearances between components for any hip position. An idealized tapered wedge stem with a 132° neck angle and a 36-mm femoral head was used. RESULTS: Eight subjects had impingement on squatting between 21(°) and 51(°) of inclination. During object pick-up, 9 subjects had impingement with inclination and anteversion angles within the "safe zone." In low-chair rise, 8 subjects had impingement at cup inclination angles between 14.5(°) and 49.5(°). CONCLUSION: The true acetabular target for impingement-avoidance motion is much smaller than previously believed and varies considerably between patients. Certain activities, such as picking up an object, low-chair rise, and squatting reduce the size of the safe zone. This study supports the need for better individualized preoperative patient-specific planning and intraoperative execution for placement of the components.

Evaluation of surgical impaction technique and how it affects locking strength of the head-stem taper junction.

Cases of fretting and corrosion at the taper junction have been reported in large metal-on-metal bearing combinations, and more recently, this concern has included metal-on-polyethylene bearing combinations. Many of these patients have been revised due to adverse local tissue reaction secondary to taper corrosion. This taper corrosion-related adverse local tissue reaction seems to be a multifactorial issue and difficult to assess. The aim of this study was to look at one potential variable, the impaction behavior (impaction force, number of blows, etc.) of orthopedic surgeons, and understand how this can affect the locking strength of tapers. A group of experienced orthopedic surgeons were asked to use their typical surgical approach to impact a femoral head onto a hip femoral stem using an Operating Room (OR)-simulated test setup. Impaction parameters such as impaction force, velocity, and energy, as well as the number of impacts, were characterized and applied in a bench-top study used to evaluate the effect of these parameters on the initial stability of the taper junction. High variation was found in the surgical impaction parameters, but overall it was determined that increased impaction force correlated to superior stability of the taper junction.

Friction in modern total hip arthroplasty bearings: Effect of material, design, and test methodology.

The purpose of this study was to characterize the effect of a group of variables on frictional torque generated by acetabular components as well as to understand the influence of test model. Three separate test models, which had been previously used in the literature, were used to understand the effect of polyethylene material, bearing design, head size, and material combinations. Each test model differed by the way it simulated rotation of the head, the type of frictional torque value it reported (static vs. dynamic), and the type of motion simulated (oscillating motion vs. continuous motion). It was determined that not only test model may impact product ranking of fictional torque generated but also static frictional torque may be significantly larger than a dynamic frictional torque. In addition to test model differences, it was discovered that the frictional torque values for conventional and highly cross-linked polyethylenes were not statistically significantly different in the more physiologically relevant test models. With respect to bearing design, the frictional torque values for mobile bearing designs were similar to the 28-mm diameter inner bearing rather than the large diameter outer liner. Testing with a more physiologically relevant rotation showed that frictional torque increased with bearing diameter for the metal on polyethylene and ceramic on polyethylene bearings but remained constant for ceramic on ceramic bearings. Finally, ceramic on ceramic bearings produced smaller frictional torque values when compared to metal on polyethylene and ceramic on polyethylene groups.

Dual mobility bearings withstand loading from steeper cup-inclinations without substantial wear.

Steep cup abduction angles with adverse joint loading may increase traditional polyethylene bearing wear in total hip arthroplasties. However, there have been few reports evaluating the effect of cup inclination on the wear of dual-mobility devices. In a hip joint simulation, we compared the short-term wear of two-sizes of modular highly cross-linked dual-mobility bearings (28 mm femoral head diameter/42 mm polyethylene insert outer diameter/54 mm acetabular shell diameter; 22.2 mm femoral head diameter/36 mm polyethylene insert outer diameter/48 mm acetabular shell diameter) at 50 and 65° of cup inclination with modular 28 mm femoral head on 54 mm cup diameter metal-on-highly cross-linked polyethylene bearings. Increasing inclination from 50-65° had no changes in volumetric wear of 28/42/54 mm (mean, 1.7 vs. 1.2 mm3 /million cycles, respectively; p = 0.50) and 22.2/36/48 mm (mean, 1.7 vs. 1.2 mm3/million cycles, respectively; p = 0.48) dual mobility bearings. At 65°, 22.2/36/48 mm dual-mobility bearings had lower volumetric loss (mean, 2.2 vs. 6.3 mm(3) ; p = 0.03) and wear rates (mean, 1.2 vs. 2.7 mm3/million cycles; p = 0.02) compared to metal-on-highly cross-linked polyethylene bearings. Modern-generation dual-mobility designs with highly cross-linked polyethylenes may potentially withstand edge-loading from steeper cup-inclinations without substantial decreases in wear.

Development and verification of a cementless novel tapered wedge stem for total hip arthroplasty.

Most current tapered wedge hip stems were designed based upon the original Mueller straight stem design introduced in 1977. These stems were designed to have a single medial curvature and grew laterally to accommodate different sizes. In this preclinical study, the design and verification of a tapered wedge stem using computed tomography scans of 556 patients are presented. The computer simulation demonstrated that the novel stem, designed for proximal engagement, allowed for reduced distal fixation, particularly in the 40-60 year male population. Moreover, the physical micromotion testing and finite element analysis demonstrated that the novel stem allowed for reduced micromotion. In summary, preclinical data suggest that the computed tomography based stem design described here may offer enhanced implant fit and reduced micromotion.

Relative head size increase using an anatomic dual mobility hip prosthesis compared to traditional hip arthroplasty: impact on hip stability.

Smaller head sizes and head/cup ratios make cups smaller than 50mm and larger than 58mm, more prone to dislocation. Using computer modeling, we compared average head sizes and posterior horizontal dislocation distance (PHDD) in two 78-patient matched cohorts. Cup sizes were small (≤50mm) or large (≥58mm). The control cohort had conventional fixed bearing prostheses, while the experimental cohort had anatomical dual mobility (ADM) hip prostheses. ADM cups have larger average head sizes and PHDD than traditional fixed bearing prostheses by 11.5mm and 80% for cups ≤50mm, and 16.3mm and 90% for cups ≥58mm. Larger head sizes and increased head/cup ratio may allow the ADM prosthesis to reduce the incidence of dislocation.

Innovations in hip arthroplasty three-dimensional modeling and analytical technology (SOMA).

The modern generations of cementless hip arthroplasty implant designs are based on precise fit and fill of components within the native bony geometry of the proximal femur and the acetabulum for enhanced implant longevity. Variations exist based on a number of population demographics such as age, gender, body mass index, and ethnicity. Recently, establishment of comprehensive electronic computerized tomographic databases from a diverse population worldwide have been key innovations in the field of implant development. This technology provides a potential improvement compared to historical techniques of implant design and manufacturing which involved limited trials on cadavers. Segmentation of the computerized data to generate three-dimensional models allows precise and accurate measurements of anatomical structures and may provide better understanding of anthropometric variations that occur among individuals. Evidence-and population-based computational analyses may provide a better tool for designing orthopaedic implants that deliver an enhanced fit for a more diverse patient population. Moreover, these population-based databases can also verify new designs by means of virtual implantation and analysis on specific or large groups of bones within the database. The aim of this paper is to describe a three dimensional modeling and analytical technology and to review the various applications of this technology in relation to hip arthroplasty.

Does dual-mobility cup geometry affect posterior horizontal dislocation distance?

BACKGROUND: Dual-mobility acetabular cups have been marketed with the purported advantages of reduced dislocation rates and improvements in ROM; however, the relative efficacies of these designs in terms of changing joint stability via ROM and dislocation distance have not been thoroughly evaluated. QUESTIONS/PURPOSES: In custom computer simulation studies, we addressed the following questions: (1) Do variations in component geometry across dual-mobility designs (anatomic, modular, and subhemispheric) affect the posterior horizontal dislocation distances? (2) How do these compare with the measurements obtained with standard hemispheric fixed bearings? (3) What is the effect of head size on posterior horizontal dislocation distances for dual-mobility and standard hemispheric fixed bearings? (4) What are the comparative differences in prosthetic impingement-free ROM between three modern dual-mobility components (anatomic, modular, and subhemispheric), and standard hemispheric fixed bearings? METHODS: CT scans of an adult pelvis were imported into computer-aided design software to generate a dynamic three-dimensional model of the pelvis. Using this software, computer-aided design models of three dual-mobility designs (anatomic, modular, and subhemispheric) and standard hemispheric fixed bearings were implanted in the pelvic model and the posterior horizontal dislocation distances measured. Hip ROM simulator software was used to compare the prosthetic impingement-free ROMs of dual-mobility bearings with standard hemispheric fixed-bearing designs. RESULTS: Variations in component design had greater effect on posterior horizontal dislocation distance values than increases in head size in a specific design (p < 0.001). Anatomic and modular dual-mobility designs were found to have greater posterior horizontal dislocation distances than the subhemispheric dual-mobility and standard hemispheric fixed-bearing designs (p < 0.001). Increasing head sizes increased posterior horizontal dislocation distances across all designs (p < 0.001). The subhemispheric dual-mobility implant was found to have the greatest prosthetic impingement-free ROM among all prosthetic designs (p < 0.001; R(2) = 0.86). CONCLUSIONS: The posterior horizontal dislocation distances differ with the individual component geometries of dual-mobility designs, with the anatomic and modular designs showing higher posterior horizontal dislocation distances compared with subhemispheric dual-mobility and standard hemispheric fixed-bearing designs. CLINICAL RELEVANCE: Static, three-dimensional computerized simulation studies suggest differences that may influence the risk of dislocation among components with varying geometries, favoring anatomic and modular dual-mobility designs. Clinical studies are needed to confirm these observations.

Radiographic fit and fill analysis of a new second-generation proximally coated cementless stem compared to its predicate design.

The purpose of this study was to compare in vivo fit and fill analysis of a new second-generation proximally coated cementless stem compared to its predicate design. This prospective trial of 100 total hip arthroplasties compared specific radiographic "Fit and Fill" parameters between the two designs. Fit type was assessed by comparing the type of canal fill. Post-operative fill parameters such as mean stem-to-canal ratios and mean minimum and maximum gaps between the stems to the cortical bone in different sections and areas were compared. A significantly higher proportion of the second-generation stems had Type I fit (82% vs. 54%), had better stem to canal fill ratio in the middle (90.6% vs. 85.3%) and distal sections (88.1% vs. 78.6%) compared to the older design. The new second-generation stem design had a significantly better canal fit and distal canal fill in the medial and lateral portions.

Wear performance evaluation of a contemporary dual mobility hip bearing using multiple hip simulator testing conditions.

The dual mobility hip bearing concept combines a small bearing with a large diameter bearing through a dual articulation system, potentially increasing the stability of the hip. Bearings with two articulations introduce concerns of whether or not wear might be increased compared to a conventional bearing. We therefore evaluated the wear performance of a dual mobility hip bearing using sequentially cross-linked and annealed polyethylene under the conditions of impingement, abrasion, and when the mobile liner becomes immobilized at either the inner or outer diameter. We found the wear performance of this dual mobility hip is dictated by the conditions experienced by the smaller inner articulation and by the polyethylene material. The highest wearing group wore 75% less than a single articulating conventional gamma/inert polyethylene bearing.

What factors affect posterior dislocation distance in THA?

BACKGROUND: Dislocation remains common after total hip arthroplasty. Efforts have been made to identify and minimize risk factors. One such factor, jump distance, or the distance the femoral head must travel before dislocating, has been poorly characterized with respect to three-dimensional kinematics. QUESTIONS/PURPOSES: We therefore determined: (1) the three-dimensional stability of four different component designs; (2) whether the degree of abduction and anteversion affects the stability; (3) whether pelvic inclination angles affected stability; and (4) which combination of these three factors had the greatest stability. METHODS: We created a positionable three-dimensional model of a THA. Acetabular components were modeled in various abduction and anteversion angles and in two different pelvic inclinations which simulate standing and chair-rising activities. RESULTS: The posterior horizontal dislocation distance increased as inclination angle and femoral head size increased. The 48-mm resurfacing typically had lower jump distances and was at risk of posterior edge loading at 30° inclination. The highest jump distance for all positions and activities occurred with the dual-mobility bearing. CONCLUSION: These findings suggest that monoblock cups require extremely accurate positioning for low dislocation risk and that pelvic orientation may increase dislocation risks. CLINICAL RELEVANCE: As a result of the dual-mobility designs having the greatest resistance to dislocation, these cups may be appropriate for patients who are at risk for dislocation in difficult primary situations and in revision hip arthroplasty procedures in which proper component orientation may be less likely to be achieved.

Comparing the accuracy of radiographic preoperative digital templating for a second- versus a first-generation THA stem.

This study assessed the accuracy of preoperative digital templating for a second-generation cementless stem compared with its first-generation design. A prospective cohort of 100 consecutive patients who had undergone a primary total hip arthroplasty using a new second-generation cementless stem was compared with the prior 100 hips that had received the first-generation stem. The authors believe that the second-generation stem may allow equal or more accurate digital templating compared with its predicate design.

Bearing surfaces for hip arthroplasty - is metal-on-metal a passing fancy?

Metal-on-metal bearings have had popularity that has waxed and waned over the years. The advantages realized relative to wear resistance and strength had been offset by early failures, manufacturing difficulty, and most recently by adverse soft tissue responses to the metallic debris. The bearing's history, evolution, advantages and disadvantages will be discussed in attempt to answer the question: is metal-on-metal a passing fancy?

Effect of ion implantation on the tribology of metal-on-metal hip prostheses.

Nitrogen ion implantation (which considerably hardens the surface of the bearing) may represent one possible method of reducing the wear of metal-on-metal (MOM) hip bearings. Currently there are no ion-implanted MOM bearings used clinically. Therefore a physiological hip simulator test was undertaken using standard test conditions, and the results compared to previous studies using the same methods. N2-ion implantation of high carbon cast Co-Cr-Mo-on-Co-Cr-Mo hip prostheses increased wear by 2-fold during the aggressive running-in phase compared to untreated bearing surfaces, plus showing no wear reductions during steady-state conditions. Although 2 specimens were considered in the current study, it would appear that ion implantation has no clinical benefit for MOM.