Effect of meniscus replacement fixation technique on restoration of knee contact mechanics and stability.

The menisci are important biomechanical components of the knee. We developed and validated a finite element model of meniscal replacement to assess the effect of surgical fixation technique on contact behavior and knee stability. The geometry of femoral and tibial articular cartilage and menisci was segmented from magnetic resonance images of a normal cadaver knee using MIMICS (Materialise, Leuven, Belgium). A finite element mesh was generated using HyperWorks (Altair Inc, Santa Ana, CA). A finite element solver (Abaqus v6.9, Simulia, Providence, RI) was used to compute contact area and stresses under axial loading and to assess stability (reaction force generated during anteroposterior translation of the femur). The natural and surgical attachments of the meniscal horns and peripheral rim were simulated using springs. After total meniscectomy, femoral contact area decreased by 26% with a concomitant increase in average contact stresses (36%) and peak contact stresses (33%). Replacing the meniscus without suturing the horns did little to restore femoral contact area. Suturing the horns increased contact area and reduced peak contact stresses. Increasing suture stiffness correlated with increased meniscal contact stresses as a greater proportion of tibiofemoral load was transferred to the meniscus. A small incremental benefit was seen of simulated bone plug fixation over the suture construct with the highest stiffness (50 N/mm). Suturing the rim did little to change contact conditions. The nominal anteroposterior stiffness reduced by 3.1 N/mm after meniscectomy. In contrast to contact area and stress, stiffness of the horn fixation sutures had a smaller effect on anteroposterior stability. On the other hand suturing the rim of the meniscus affected anteroposterior stability to a much larger degree. This model emphasizes the importance of the meniscus in knee biomechanics. Appropriate meniscal replacement fixation techniques are likely to be critical to the clinical success of meniscal replacement. While contact conditions are mainly sensitive to meniscus horn fixation, the stability of the knee under anteroposterior shear loads appeared to be more sensitive to meniscal rim fixation. This model may also be useful in predicting the effect of biomaterial mechanical properties and meniscal replacement shape on knee contact conditions.

A nonlinear viscoelastic finite element model of polyethylene.

A nonlinear viscoelastic finite element model of ultra-high molecular weight polyethylene (UHMWPE) was developed in this study. Eight cylindrical specimens were machined from ram extruded UHMWPE bar stock (GUR 1020) and tested under constant compression at 7% strain for 100 sec. The stress strain data during the initial ramp up to 7% strain was utilized to model the "instantaneous" stress-strain response using a Mooney-Rivlin material model. The viscoelastic behavior was modeled using the time-dependent relaxation in stress seen after the initial maximum stress was achieved using a stored energy formulation. A cylindrical model of similar dimensions was created using a finite element analysis software program. The cylinder was made up of hexahedral elements, which were given the material properties utilizing the "instantaneous" stress-strain curve and the energy-relaxation curve obtained from the experimental data. The cylinder was compressed between two flat rigid bodies that simulated the fixtures of the testing machine. Experimental stress-relaxation, creep and dynamic testing data were then used to validate the model. The mean error for predicted versus experimental data for stress relaxation at different strain levels was 4.2%. The mean error for the creep test was 7% and for dynamic test was 5.4%. Finally, dynamic loading in a hip arthroplasty was modeled and validated experimentally with an error of 8%. This study establishes a working finite element material model of UHMWPE that can be utilized to simulate a variety of postoperative arthroplasty conditions.

Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use.

AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.

Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study.

BACKGROUND: Prophylaxis is recommended following total joint replacement because of the high risk of venous thromboembolism (VTE). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected deep vein thrombosis (DVT) to about 10-15% in total hip replacement (THR) patients. Ximelagatran is a novel, oral direct thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. We compared the efficacy and safety of ximelagatran with those of enoxaparin for the prevention of VTE in patients undergoing THR. METHODS: This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. Patients received fixed-dose oral ximelagatran 24 mg bid or subcutaneous enoxaparin 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of VTE (by postoperative day 12) included thrombosis determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven DVT or pulmonary embolism (PE). VTE and bleeding events were interpreted by an independent central adjudication committee for primary analysis. RESULTS: Of the 1838 patients randomized, 1557 had either adequate venography or symptomatic, proven VTE (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total VTE were 7.9% (62 of 782 patients) in the ximelagatran group and 4.6% (36 of 775 patients) in the enoxaparin group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal DVT and/or PE occurred in 3.6% (28 of 782 patients) in the ximelagatran group and 1.2% (nine of 774 patients) in the enoxaparin group. Major bleeding events were observed in 0.8% (seven of 906) of the ximelagatran-treated patients and in 0.9% (eight of 910) of the enoxaparin-treated patients (P > 0.95). Non-inferiority of ximelagatran 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the enoxaparin regimen. CONCLUSIONS: Both ximelagatran and enoxaparin decreased the overall rate of VTE compared with that reported historically. However, in this study, enoxaparin 30 mg bid was more effective than ximelagatran 24 mg bid for prevention of VTE in THR. Oral ximelagatran was used without coagulation monitoring, was well tolerated, and had bleeding rates comparable to those of enoxaparin. Further refinement by testing a higher dose of ximelagatran in the patients undergoing THR is warranted.

Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study.

BACKGROUND: Up to one third of patients who undergo total knee replacement develop deep vein thrombosis after surgery despite receiving low-molecular-weight heparin prophylaxis. Ximelagatran is a novel direct inhibitor of free and clot-bound thrombin. METHODS: We performed a randomized, parallel, dose-finding study of 600 adults undergoing elective total knee replacement at 68 North American hospitals to determine the optimum dose of ximelagatran to use as prophylaxis against venous thromboembolism after total knee replacement. Patients received either ximelagatran twice daily by mouth in blinded fixed doses of 8, 12, 18, or 24 mg or open-label enoxaparin sodium, 30 mg, subcutaneously twice daily, starting 12 to 24 hours after surgery and continuing for 6 to 12 days. We measured the 6- to 12-day cumulative incidence of symptomatic or venographic deep vein thrombosis, symptomatic pulmonary embolism, and bleeding. RESULTS: A total of 594 patients received at least 1 dose of the study drug; 443 patients were evaluable for efficacy. Rates of overall venous thromboembolism (and proximal deep vein thrombosis or pulmonary embolism) for the 8-, 12-, 18-, and 24-mg doses of ximelagatran were 27% (6.6%), 19.8% (2.0%), 28.7% (5.8%), and 15.8% (3.2%), respectively. Rates of overall venous thromboembolism (22.7%) and proximal deep vein thrombosis or pulmonary embolism (3.1%) for enoxaparin did not differ significantly compared with 24-mg ximelagatran (overall difference, -6.9%; 95% confidence interval, -18.0% to 4.2%; P=.3). There was no major bleeding with administration of 24 mg of ximelagatran twice daily. CONCLUSION: Fixed-dose, unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be safe and effective oral prophylaxis against venous thromboembolism after total knee replacement.

Polyethylene wear and variations in knee kinematics.

A six-station knee wear simulator was used to test a posterior cruciate-retaining total knee arthroplasty design. Six implants each were tested in three groups; low intensity, high intensity, and malalignment using kinematic inputs from normal gait data, more severe loading conditions, and 3 degrees varus malalignment, respectively. For each group, gravimetric wear of the polyethylene inserts was measured for 5,000,000 cycles. Knee wear testing showed significantly different results for the three groups. Low intensity group inserts had mean wear rates of 3.1 (+/- 1.2) mg per million cycles. High intensity group inserts had significantly higher mean wear rates of 7.4 (+/- 2.7) mg per million cycles. Malalignment group inserts had the highest wear rates of 9.2 (+/- 3.3) mg per million cycles. The wear generated in the knee simulator seems to be dependent on the relative motions and loads at the articulating surface. The high intensity groups were subjected to motions that included reciprocating anteroposterior translations and a higher peak axial load than the low intensity group. This resulted in increasing the amount of wear. Varus malalignment also increased the total wear significantly. These results may explain some of the wide variations in wear seen in retrieved knee implants.

Quadriceps moment arm and quadriceps forces after total knee arthroplasty.

Knee prosthetic designs that increase quadriceps moment arm can reduce quadriceps tension and patellofemoral compressive forces. Six knees from cadavers were tested on the Oxford knee rig, which simulates closed chain knee extension under load. Three conditions were tested sequentially for each knee: Normal, Control (implanted with the Osteonics 7000 knee design), and Scorpio (implanted with the Osteonics Scorpio design). The center of flexion-extension of the Scorpio design was 10 mm posterior to that of Control that served to lengthen the quadriceps moment arm. An electromagnetic tracking system measured dynamic knee kinematics, and a uniaxial load cell measured quadriceps tension. The Scorpio design reduced quadriceps tension when compared with the Normal or Control knee ranging from 5% to 20%. This was statistically significant at flexion angles greater than 50 degrees. In three knees, the patellar component was instrumented with a triaxial load cell that measured patellofemoral forces. Patellofemoral forces were lower with the Scorpio design compared with the Control. Increasing quadriceps lever arm reduces quadriceps forces and can facilitate activities of daily living and enhance patient rehabilitation. Reduced quadriceps forces may result in reduced patellofemoral forces that can have a beneficial effect on anterior knee pain, patellar component wear, and loosening.

Polyethylene contact stresses, articular congruity, and knee alignment.

Increased conformity at the tibiofemoral articulation increases contact area and reduces contact stresses in total knee arthroplasty. Malalignment, however, can increase polyethylene contact stresses. The effect of knee alignment and articular conformity on contact stresses was evaluated in a finite element model. The polyethylene insert and femoral component were modeled in high- and low-conformity conditions. An axial tibial load of 3000 N was applied across the tibiofemoral articulation at different knee positions ranging from 0 degrees, to 90 degrees, flexion, 0 to 10 mm anteroposterior translation, 0 degrees to 10 degrees axial rotation, and coronal plane angulation (liftoff). Increased conformity significantly reduced contact stresses in neutral alignment (by 44% at 0 degrees flexion and 36% at 60 degrees and 90 degrees flexion). Liftoff significantly increased contact stresses in low- and high-conformity conditions, but to a lesser degree in the high-conformity condition. Malalignment in rotation was most detrimental especially with the high-conformity insert design. Overall, increasing articular conformity reduced stresses when the knee was well-aligned. However, malalignment in axial rotation was detrimental. Mobile-bearing knee designs with increased articular congruity may result in lower contact stresses, especially the rotating-bearing designs that theoretically minimize rotational malalignment.

Low molecular weight heparin prophylaxis in total knee arthroplasty: the answer.

Venous thrombosis continues to be a major risk after total knee arthroplasty. Without prophylaxis, the prevalence of deep vein thrombosis is as high as 84%, with proximal occurrence as high as 20%. Of more concern is the occurrence of pulmonary embolism as high as 7%, with fatal pulmonary embolism as high as 0.7%. This high prevalence mandates that prophylaxis for thromboembolic disease be used for patients undergoing total knee arthroplasty. Low molecular weight heparin has been studied extensively and is safe and effective prophylaxis after total knee arthroplasty. Low molecular weight heparins have a predictable dose response, offer high bioavailability at low doses, and produce linear pharmacokinetics. It has a half-life of approximately 4.5 hours providing effective dosing every 12 to 24 hours with rapid antithrombotic action. Routine pharmacologic prophylaxis with low molecular weight heparin seems to be effective in decreasing the occurrence of venous thromboembolism. However, venographic prevalence of deep vein thrombosis among patients undergoing total knee arthroplasty and receiving prophylaxis remains substantial at 30.6%. Prophylaxis with low molecular weight heparin beyond hospitalization may be indicated with decreased hospital stays, although studies have not been convincing that extended outpatient prophylaxis for more then 7 to 10 days is necessary.

In vivo changes after mechanical injury.

Chondrocytes undergo apoptosis in response to mechanical injury in vitro. The current clinical study correlates arthroscopic and magnetic resonance imaging results with biopsy specimens of cartilage from patients with knee injury. Twenty patients were evaluated at a mean 2.7 months after acute knee injury. The mean age of the patients was 32 years and the mean weight was 83 kg. Cartilage lesions were graded separately on magnetic resonance images and arthroscopy in a blinded manner. During arthroscopy, a 1.8 mm diameter biopsy specimen was obtained from the edge of cartilage lesion. The biopsy specimen underwent histologic examination by safranin O staining and detection of chondrocyte apoptosis by the presence of deoxyribonucleic acid fragmentation. There was a positive correlation in 50% (10 of 20) when the presence or absence of cartilage lesions by magnetic resonance imaging was correlated with arthroscopy. All cases of partial thickness or full-thickness cartilage loss that were seen by arthroscopy also were detected by magnetic resonance images. Apoptotic cells were significantly more numerous in biopsy specimens from lesions compared with control biopsy specimens. The findings of reduced cell viability attributable to apoptosis may have profound implications for cartilage repair. This opens potential therapeutic avenues for the treatment of posttraumatic cartilage lesions through apoptosis prevention.

Impact of mechanical trauma on matrix and cells.

Posttraumatic arthritis is one of the most common causes of secondary osteoarthritis. The contribution of cell death to matrix degradation has not been characterized fully. The current study was designed to determine the effect of mechanical injury on chondrocyte viability and matrix degradation. Full-thickness bovine and human cartilage explants, 5 mm in diameter were subjected to mechanical loads representative of traumatic joint injury. Glycosaminoglycan release and percent apoptotic cells were measured. Unilateral patellas in eight anesthetized rabbits were subjected to an impact load. Rabbits were euthanized at 96 hours after injury and patellar cartilage was harvested for analysis. The effect of a pan-caspase inhibitor, z-VAD.fmk [benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone] in preventing chondrocyte apoptosis in human articular cartilage explants was determined. A significant increase in the number of apoptotic cells was observed in response to mechanical loading. The mean in vivo apoptotic rates were 1% in control rabbits and 15% in impacted patellas. Caspase inhibition reduced chondrocyte apoptosis from 34% to 25% after mechanical injury and was associated with reduction in glycosaminoglycan release. Mechanical injury induces chondrocyte apoptosis that is sensitive to pharmacologic inhibition. This identifies a new approach to limit traumatic cartilage injury and the subsequent development of secondary osteoarthritis.

Patellar tracking in total knee arthroplasty: inset versus onset design.

Patellar components come in onset and inset designs. Kinematic differences between these designs were studied in a cadaver model of closed kinetic chain knee extension. Seven frozen knees were implanted with a standard posterior cruciate-retaining design. Each knee first was tested with the inset design, followed by the onset design in the Oxford Knee Rig. Three-dimensional tracking of the femur, tibia, and patella was performed using an electromagnetic system during active knee extension under load. No statistically significant differences were seen in knee kinematics between the 2 designs. The inset patella tended to shift laterally and tilt laterally more than the onset patella. This difference may be clinically significant.