Medial unicompartmental knee arthroplasty in ACL-deficient knees is a viable treatment option: in vivo kinematic evaluation using a moving fluoroscope.

PURPOSE: Unicompartmental knee arthroplasty (UKA), resulting in similar kinematics to native knees, is functionally superior to total knee arthroplasty (TKA). However, ACL deficiency is generally considered to be a contraindication. The main purpose of this study was to investigate if UKA in ACL-deficient knees would result in similar kinematics to conventional UKA with an intact ACL. METHODS: Ten conventional UKA patients were compared to eight ACL-deficient patients with a reduced tibial slope to compensate for instability, resulting from the deficient ACL. Knee kinematics was evaluated with a moving fluoroscope, tracking the knee joint during daily activities. In a standing position (baseline), posterior shift of the femur was observed for ACL-deficient UKA patients, compared to conventional UKA patients. RESULTS: A significant posterior femoral shift in the ACL-deficient group was observed during the first 25% (near extension) of deep knee bend, while there was no difference in kinematic waveforms for all other activities. No significant range of motion differences across different activities between the two UKA groups were detected, except for an increase of medial AP translation in the ACL-deficient group, during deep knee bend and stair descent. CONCLUSION: Despite the posterior femoral shift due to ACL deficiency, both UKA groups showed similar kinematic waveforms, indicating that posterior tibial slope reduction can partially compensate for ACL function. This supported our hypothesis that fixed bearing UKA can be a viable treatment option for selected ACL-deficient patients, allowing patient-specific kinematics. While anteroposterior laxity can be compensated, rotational stability was a prerequisite for this approach. LEVEL OF EVIDENCE: III.

Skin crease 'bikini' incision for anterior approach total hip arthroplasty: surgical technique and preliminary results.

BACKGROUND: The direct anterior approach for THA allows implantation through an internervous plane without muscle detachment from bone. However, the classic longitudinal skin incision does not follow the anatomic skin creases and can result in scar widening. We therefore modified our incision technique to a short oblique skin incision following the anatomic skin crease of the groin. QUESTIONS/PURPOSES: We sought to determine whether (1) the oblique incision leads to improved scar results compared with the longitudinal incision, (2) functional and pain scores are similar between the two approaches, and (3) the new incision is safe with respect to complications, blood loss, implant position, and lateral femoral cutaneous nerve (LFCN) symptoms. METHODS: Fifty-nine patients underwent THAs using either the classic (n = 33) or the new oblique incision (n = 26). At 6 months after surgery, we compared objective and subjective scar results, WOMAC, Oxford Hip and UCLA scores, blood loss, cup inclination, and the presence of LFCN symptoms between both groups. RESULTS: Objectively, the modified incision resulted in significantly shorter and narrower scars. Subjectively, patients in the modified incision group were substantially more satisfied with the aesthetic appearance. Functional and pain scores were similar. No complications occurred in either group. Blood loss and cup inclination did not differ between the two groups. There were no differences in LFCN symptoms. CONCLUSIONS: In this series, which selected for thinner patients in the study group, the 'bikini' incision for an anterior approach THA led to improved scar cosmesis and was found to be safe in terms of blood loss, appropriate component placement, and risk for LFCN injury. LEVEL OF EVIDENCE: Level III, retrospective comparative study. See the Guidelines for Authors for a complete description of levels of evidence.

Retention treatment after periprosthetic total hip arthroplasty infection.

PURPOSE: The purpose of this study was to compare infection control rates between implant retention and two-stage revision and assess the effectiveness of retention treatment in THA. METHODS: Twenty-eight debridements with implant retention (retention group) and 65 staged revisions (removal group) were retrospectively analysed and risk factors that can contribute to failure of infection control were explored. RESULTS: For the retention and removal groups, infection control rates were 50% and 78% after initial treatment, and 68% and 82% at latest follow-up, respectively. There were no significant differences in the number of additional operative procedures, total length of hospital stay, and duration of treatment between groups. Infection of revision THA, polybacterial and S. aureus infection were identified as risk factors for infection control. CONCLUSIONS: Retention treatment can be considered an initial treatment option in selected cases of primary THA, with a single organism, non-S. aureus infection with 50% chance of infection control and no disadvantages in terms of additional procedure, hospital stay, and treatment duration.

Can implant retention be recommended for treatment of infected TKA?

BACKGROUND: Retention treatment is reportedly associated with lower infection control rates than two-stage revision. However, the studies on which this presumption are based depend on comparisons of historical rather than concurrent controls. QUESTIONS/PURPOSES: We (1) asked whether the infection control rates, number of additional procedures, length of hospital stay, and treatment duration differed between implant retention and two-stage revision treatment; and (2) identified risk factors that can contribute to failure of infection control. METHODS: We reviewed the records of 60 patients treated for 64 infected TKA from 2002 to 2007. Twenty-eight patients (32 knees) underwent débridement with retention of component, and 32 patients (32 knees) were treated with component removal and two-stage revision surgery. We determined patients' demographics, type of infection, causative organisms, and outcome of treatment. Mean followup was 36 months (range, 12-84 months). RESULTS: Infection control rate was 31% in retention and 59% in the removal group after initial surgical treatment, and 81% and 91% at latest followup, respectively. Treatment duration was shorter in the retention group and there was no difference in number of additional surgeries and length of hospital stay. Type of treatment (retention versus removal) was the only factor associated with infection control; subgroup analysis in the retention group showed Staphylococcus aureus infection and polyethylene nonexchange as contributing factors for failure of infection control. CONCLUSIONS: Although initial infection control rate was substantially lower in the retention group than the removal group, final results were comparable at latest followup. We believe retention treatment can be selectively considered for non-S. aureus infection, and when applied in selected patients, polyethylene exchange should be performed. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Reliability and validity of the cross-culturally adapted German Oxford hip score.

UNLABELLED: There is currently no German version of the Oxford hip score. Therefore we sought to cross-culturally adapt and validate the Oxford hip score for use with German-speaking patients (OHS-D) with osteoarthritis of the hip using a forward-backward translation procedure. We then assessed the new score in 105 consecutive patients (mean age, 63.4 years; 48 women) undergoing THA. We specifically determined: the number of fully completed questionnaires, reliability, concurrent validity by correlation with the WOMAC, Harris hip score, and SF-12, and distribution of floor and ceiling effects. We received 96.6% fully completed questionnaires. An intraclass correlation coefficient of 0.90 and Cronbach's alpha of 0.87 suggested the OHS-D was reliable. Correlation coefficients between the OHS-D and the WOMAC total score, pain subscale, stiffness subscale, and physical function subscale were 0.82, 0.70, 0.68, and 0.82, respectively. OHS-D correlated with the Harris hip score (r = 0.63) and the physical component scale of the SF-12 (r = 0.58). We observed no ceiling or floor effects. The OHS-D appeared a reliable and valid measurement tool for assessing pain and disability with German-speaking patients with hip osteoarthritis. LEVEL OF EVIDENCE: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Patellar height before and after unicompartmental knee arthroplasty: association with early clinical outcome?

INTRODUCTION: There is paucity of information available concerning the role of patellar height in unicompartmental knee arthroplasty (UKA). The present study was conducted to determine the patellar height before and after UKA and to assess possible effects on the early clinical outcome. MATERIALS AND METHODS: We measured the patellar height before and after UKA in 83 consecutive knees using the Blackburne-Peel (BP) index and Insall-Salvati (IS) ratio and investigated the impact of the patellar height on the clinical outcome 2 years after surgery. RESULTS: BP values significantly decreased from 0.81 before surgery to 0.76 postoperatively (P < 0.001). IS ratios did not significantly decrease from 1.02 to 1.01 (P = 0.108). Lower preoperative BP values were negatively correlated with the postoperative knee extension (r = -0.357, P = 0.026), while higher preoperative BP values were negatively associated with the postoperative Knee Society Score (r = -0.302, P = 0.046). Lower preoperative IS values were negatively correlated with postoperative Knee Scores (r = -0.394, P = 0.019). CONCLUSION: After UKA, the patellar height decreased significantly according to the BP index, but not significantly according to the IS ratio. We found only weak and inconsistent correlations between the patellar height and clinical outcome parameters. Hence, based on the present results, the patellar height seems not to be a strict separate patient-selection criterion for UKA.

Association of body mass index and clinical outcome 2 years after unicompartmental knee arthroplasty.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has gained in popularity during the last years. However, the body mass index (BMI) of patients undergoing UKA is controversially discussed in the literature. There is, moreover, a paucity of information available concerning the association of BMI with early clinical outcomes after UKA. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 83 consecutive UKA, 2 years after surgery, and investigated the potential association of BMI and the outcome variables Knee Society Score (KSS), University of California at Los Angeles (UCLA) activity levels, anterior knee pain (AKP), range of motion, and implant failure. RESULTS: The KSS and UCLA significantly increased from 132 and 4.7 preoperatively to 187.5 and 7.1, respectively, after surgery. Knee flexion significantly improved from 123.7 to 128.4 degrees and the prevalence of extension deficiencies significantly decreased from 28.9 to 15.7%. Three knees (3.6%) failed and were converted to total knee arthroplasty. Failures were not associated with increased BMI (P = 0.387). The BMI had no significant association with KSS values, UCLA levels, and implant failure. We found a weak negative correlation between BMI and postoperative knee flexion (r = -0.285, P = 0.009) and a moderate positive correlation between BMI and the intensity of AKP (r = 0.525, P < 0.001). CONCLUSION: The results of the present study suggest that the BMI of patients undergoing UKA has no major impact on the early clinical outcome 2 years after surgery. There was, however, a definite correlation between the BMI and AKP. Longer follow-up is necessary to determine if overweight and obesity may increase revision rates after UKA.

Is ACL deficiency always a contraindication for medial UKA? Kinematic and kinetic analysis of implanted and contralateral knees.

BACKGROUND: Prevalence of knee osteoarthritis increases because life expectancy continues to rise with an active patient population. Hence, the concept of unicompartmental knee arthroplasty (UKA) has regained popularity as a treatment option for unicompartmental knee osteoarthritis. Anterior cruciate ligament (ACL) deficiency is widely considered as a contraindication for UKA, however, there are conflicting reports. If otherwise indicated, some surgeons consider UKA for ACL-deficient patients using a modified surgical technique, with a reduction of posterior tibial slope. RESEARCH QUESTION: The purpose of this study was to evaluate outcomes in UKA patients with ACL deficiency in comparison to a conventional UKA group (intact ACL) by the measurement of knee kinematics and kinetics. METHODS: Ten patients with conventional UKA and an intact ACL and eight patients with an ACL-deficient UKA and a reduced posterior tibial slope relative to the native knee were recruited. Three-dimensional joint kinematics of the knee were measured, using skin markers and an infrared optical motion capture system. Ground reaction forces (GRF) were measured with force plates in all three directions. Level walking, ramp descent and stair descent were analyzed, comparing implanted and contralateral native knees and the two UKA groups. RESULTS: No significant differences in kinetics and kinematics were observed between conventional UKA and ACL-deficient UKA groups for any of the activities. However, some asymmetries in GRF between the implanted and contralateral side were present for the ACL-deficient group, during level walking (unloading rate) and stair descent (stance time). SIGNIFICANCE: Promising outcomes of the ACL-deficient UKA group suggest that ACL deficiency may not always be a contraindication. Therefore, ACL-deficient UKA could be an alternative treatment option to total knee arthroplasty for an appropriate surgeon selected patient population.

Short-term functional advantages after medial unicompartmental versus total knee arthroplasty.

BACKGROUND: There are many uncertainties about the advantages and disadvantages of using unicompartmental (UKA) versus total knee arthroplasty (TKA) to treat patients with knee osteoarthritis. It is important to have sufficient early postoperative quadriceps strength for long-term, self-reported and gait-related outcomes after knee arthroplasty, but very limited comparative data exist regarding UKA and TKA patients. METHODS: This study assessed isometric quadriceps strength, spatio-temporal gait parameters (walking speed, step length, single-limb support phase) and self-reported outcomes (pain, function, stiffness) in 18 TKA and 18 UKA patients six months after surgery, as well as in 18 healthy controls. RESULTS: Quadriceps strength of TKA, but not of UKA patients, was lower than that of controls (P < 0.05). UKA patients demonstrated better gait function in terms of a longer single-limb support phase than TKA patients (P < 0.01), which agreed with better self-reported pain (P < 0.05), function (P < 0.01) and stiffness (P < 0.05) scores compared to TKA patients. CONCLUSIONS: Six months after surgery, UKA patients showed better short-term quadriceps strength and gait function compared to TKA patients, together with less self-reported knee pain and stiffness. Patients eligible for UKA may experience less functional impairments compared to those who require TKA.

Polyethylene particle-induced bone resorption in alpha-calcitonin gene-related peptide-deficient mice.

UNLABELLED: This study investigates the impact of alpha-CGRP on bone metabolism after implantation of polyethylene particles. alpha-CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle-induced osteolysis. INTRODUCTION: Periprosthetic osteolysis is the major reason for aseptic loosening in joint arthroplasty. This study aimed to investigate the potential impact of alpha-calcitonin gene-related peptide (alpha-CGRP) deficiency on bone metabolism under conditions of polyethylene particle-induced osteolysis. MATERIALS AND METHODS: We used the murine calvarial osteolysis model based on polyethylene particles in 14 C57BL 6 mice and 14 alpha-CGRP-deficient mice divided into four groups of 7 mice each. Groups 1 (C57BL/J 6) and 3 (alpha-CGRP knockout) received sham surgery, and groups 2 (C57BL/J 6) and 4 (alpha-CGRP knockout) were treated with polyethylene particles. Qualitative and quantitative 3D analyses were performed using microCT. In addition, bone resorption was measured within the midline suture by histological examination. The number of osteoclasts was determined by counting the TRACP(+) cells. Calvarial bone was tested for RANKL expression by RT-PCR and immunocytochemistry. RESULTS: Bone resorption was significantly reduced in alpha-CGRP-deficient mice compared with their corresponding wildtype C57BL 6 mice as confirmed by histomorphometric data (p < 0.001) and microCT (p < 0.01). Osteoclast numbers were significantly reduced in group 3 and the particle subgroup compared with group 1 (p < 0.001). We observed a >3-fold increase of basal RANKL mRNA levels within group 1 compared with group 3. Additional low RANKL immunochemistry staining was noted in groups 3 and 4. CONCLUSIONS: In conclusion, alpha-CGRP knockout mice did not show the expected extended osteolysis compared with wildtype mice expressing alpha-CGRP. One of the most reasonable explanations for the observed decrease in osteolysis could be linked to the osteoprotegerin (OPG)/RANK/RANKL system in alpha-CGRP-deficient animals. As a consequence, the fine tuning of osteoclasts mediating resorption in alpha-CGRP-null mice may be deregulated.

Anabolic effects of bisphosphonates on peri-implant bone stock.

The long-term durability of total joint replacements is critically dependent on adequate peri-implant bone stock, which can be compromised by wear debris-mediated osteolysis. This study investigated the effects of bisphosphonates on enhancing peri-implant bone in the presence of clinically relevant ultra-high molecular weight polyethylene (UHMWPE) wear debris. Fiber-mesh coated titanium-alloy plugs were implanted bilaterally in the femoral condyles of 36 New Zealand white rabbits. Implants in the left femora were covered with submicron UHMWPE particles during surgery. Rabbits were administered either no drug, subcutaneous alendronate weekly (1.0mg/kg/week) or a single dose of intravenous zoledronate (0.015mg/kg). A total of 6/12 rabbits in each group were sacrificed at 6 weeks and the remainder at 12 weeks postoperatively. Peri-implant bone stock was analyzed radiographically and histomorphometrically. Radiographically, both bisphosphonates significantly increased periprosthetic cortical thickness at 6 weeks (p<0.0001; alendronate: +18%; zoledronate: +11%) and at 12 weeks (p=0.001; alendronate: +17%; zoledronate:+19%). Histomorphometrically, alendronate and zoledronate raised peri-implant bone volume (BV/TV) up to 2-fold after 6 weeks without added wear debris and more than 3-fold when wear debris was present. Furthermore a 6-week bisphosphonate treatment increased osteoid thickness in the absence of wear debris (alendronate: +132%, p=0.007; zoledronate: +67%, p=0.51) and in the presence of wear debris (alendronate: +134%, p=0.023; zoledronate: +138%, p=0.016). In summary, alendronate and zoledronate treatment increased periprosthetic bone stock in a rabbit femoral model, particularly in the presence of UHMWPE wear debris. These new findings suggest that bisphosphonates may more than compensate for the well-documented negative effects of wear debris on peri-implant bone stock. The combined antiresorptive and osteoanabolic effects of bisphosphonates on periprosthetic bone stock may have an important role for critically improving the biological fixation and ultimate durability of total joint arthroplasty.

Over-expression of p53/BAK in aseptic loosening after total hip replacement.

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The possible induction of apoptosis has not been addressed in great detail. Thus far, it has been shown that ceramic and polyethylene particles can induce apoptosis of macrophages in vitro. The purpose of this study was to test the hypothesis that wears debris generated from total hip arthroplasty could induce cellular damage and apoptosis in vivo. We therefore determined by immunohistochemical methods if increased expression of p53, an important transcription factor, and BAK and Bcl-2, two important regulators of apoptosis, can be found in interface membranes and capsules of hips with aseptically loose implants. Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (p < 0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris. In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.

[Pressfit of equatorially roughened cementless acetabular components--a finite element analysis]. / Der acetabuläre Pressfit bei aquatorialer Beschichtung der zementfreien Hüftpfanne--eine finite-Elemente-Analyse.

AIM: Does the pressfit anchorage of cementless acetabular cups depend on the roughness of the pole? To answer this question the primary pressfit of two cementless acetabular cups which differ only with regard to the roughness of their poles were compared by means of finite elements analysis. MATERIALS AND METHODS: It was assumed that the material properties of bone are homogeneous, isotropic and linearly elastic. Material-specific values of cancellous bone with three different bone densities were used. Assumption of isotropy represents an approximation. RESULTS: Comparison of the two prosthesis designs revealed that both designs/shapes cause similar patterns of bone deformation and tension. CONCLUSIONS: It can therefore be concluded that with regard to pressfit anchorage the prosthesis with milled polar surface is according to FEA mechanically equivalent to the prosthesis with non-milled polar surface.

Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis.

The effects of statins on bone formation in periprosthetic osteolysis have not been determined to date. We investigated the effect of the HMG-CoA reductase inhibitor simvastatin on osteoblastic bone formation under conditions of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After 2 weeks, calvaria were processed for histomorphometry and stained with Giemsa dye. New bone formation was measured as osteoid tissue area within the midline suture. Bone thickness was quantified as indicator of net bone growth. Statistical analysis was performed using one-way ANOVA and a Student's t-test. New bone formation and bone thickness were significantly enhanced following simvastatin treatment. New bone formation was 0.008+/-0.008 mm2 in sham controls (group I), 0.015+/-0.012 mm2 after particle implantation without further intervention (group II), compared to 0.083+/-0.021 mm2 with particle implantation and simvastatin treatment (group III) (p=0.003). The bone thickness was 0.213+/-0.007 mm in group I, 0.183+/-0.005 mm in group II, and 0.238+/-0.009 mm in group III (p=0.00008). In conclusion, simvastatin treatment markedly promoted bone formation and net bone growth in UHMWPE particle-induced osteolysis in a murine calvarial model. These new findings indicate that simvastatin may have favorable osteoanabolic effects on wear debris-mediated osteolysis after total joint arthroplasty, involving local stimulation of osteoblastic bone formation.

Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells.

Bisphosphonates are well known potent inhibitors of osteoclast activity and are widely used to treat metabolic bone diseases. Recent evidence from in vitro and in vivo studies indicates that bisphosphonates may additionally promote osteoblastic bone formation. In this study, we evaluated the effects of three FDA-approved and clinically utilized bisphosphonates, on the proliferation and osteogenic differentiation of human bone marrow stromal cells (BMSC). BMSC were obtained from patients undergoing primary total hip arthroplasty for end-stage degenerative joint disease. Cells were treated with or without a bisphosphonate (alendronate, risedronate, or zoledronate) and analyzed over 21 days of culture. Cell proliferation was determined by direct cell counting. Osteogenic differentiation of BMSC was assessed with alkaline phosphatase bioassay and gene expression analyses using conventional RT-PCR as well as real-time quantitative RT-PCR. All bisphosphonates tested enhanced the proliferation of BMSC after 7 and 14 days of culture. Steady-state mRNA levels of key genes involved in osteogenic differentiation such as bone morphogenetic protein-2 (BMP-2), bone sialoprotein-II, core-binding factor alpha subunit 1 (cbfa1) and type 1 collagen, were generally increased by bisphosphonate treatment in a type- and time-dependent manner. Gene expression levels varied among the different donors. Enhancement of osteogenic differentiation was most pronounced after 14 days of culture, particularly following zoledronate treatment (p < 0.05 for BMP-2). In conclusion, using a clinically relevant in vitro model we have demonstrated that bisphosphonates enhance proliferation of BMSC and initiate osteoblastic differentiation. When administered around joint replacements, bisphosphonates may potentially compensate for the deleterious effects of particulate wear debris at the bone-implant interface, by encouraging increased numbers of cells committed to the osteoblastic phenotype, and thus improve the longevity of joint replacements.

The decrease of particle-induced osteolysis after a single dose of bisphosphonate.

The most common cause of implant failure in joint replacement is aseptic loosening due to particle-induced osteolysis. Bisphosphonates have been shown to be effective against particle-induced osteolysis when administered daily. We investigated the effect of a single subcutaneous dose of a more potent third generation bisphosphonate on particle-induced osteolysis. We utilized the murine calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Twenty-eight mice were used, seven per group. Seven animals were treated with a single dose of zoledronic acid (ZA) directly after surgery and seven animals were treated four days postoperatively. For statistical analysis one-way ANOVA and a Student's t-test were used. Bone resorption was 0.26+/-0.09 mm(2) in animals with particle implantation, 0.14+/-0.05 mm(2) in animals with particle implantation and ZA treatment directly after surgery (p = 0.0047), and 0.15+/-0.05 mm(2) in animals with particle implantation and ZA treatment on the fourth postoperative day (p = 0.006). In conclusion, particle-induced bone resorption was markedly decreased by a single s.c. dose of a third generation bisphosphonate. This important new finding holds great promise, because single dose treatment of particle-induced osteolysis may reduce side effects compared to repeated application of bisphosphonates.

The effect of simvastatin on polyethylene particle-induced osteolysis.

This study aimed to investigate the effects of the HMG-CoA reductase inhibitor simvastatin on ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was used in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After two weeks, calvaria were processed for histomorphometry. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Osteoclast numbers were determined per high-power field using TRAP-staining. Statistical analysis was performed using one-way ANOVA and Student's t-test. Bone resorption in midline suture was 0.094+/-0.007 mm(2) in sham controls (group I), 0.25+/-0.025 mm(2) after particle implantation without further intervention (group II), and 0.131+/-0.02 mm(2) with particle implantation and additional simvastatin treatment (group III) (p=0.00003). Osteoclast numbers were 15.3+/-3.6 in group I, 48.7+/-7.1 in group II and 6.2+/-3.1 in group III (p=0.00002). In conclusion, simvastatin treatment markedly decreased UHMWPE particle-induced osteolysis in a murine calvarial model. This finding suggests that simvastatin may have a role for noninvasive prevention and treatment of wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.

Stimulation of bone formation by zoledronic acid in particle-induced osteolysis.

We investigated the effect of a single subcutaneous dose of zoledronic acid on particle-induced osteolysis and observed excessive regional new bone formation. We utilized the murine calvarial osteolysis model and polyethylene particles in C57BL/J6 mice. Twenty-eight mice were used, seven per group. Specimens were stained with Giemsa dye. The osteoid tissue area was determined. Bone thickness was measured as an indicator of bone growth. Net bone growth was significantly increased in animals with zoledronic acid treatment: 0.02 mm(2)+/-0.03 mm(2) in animals with particle implantation only (group 2), 0.25 mm(2)+/-0.08 mm(2) with particle implantation and zoledronic acid treatment directly after surgery (group 3; p=0.0018), and 0.21 mm(2)+/-0.11 mm(2) with particle implantation and zoledronic acid treatment on the fourth postoperative day (group 4; p=0.0042). The mean bone thickness was 0.2 mm+/-0.04 mm (range 0.17 mm-0.31 mm) in group 1 (sham controls) and 0.16 mm+/-0.02 mm (range 0.14 mm-0.19 mm) in group 2, 0.31 mm+/-0.04 mm (range 0.28 mm-0.39 mm) in group 3, and 0.29 mm+/-0.02 mm (range 0.28 mm-0.34 mm) in group 4. Student's t-test revealed a statistically significant difference between groups 2 and 3 (p=0.00042), and groups 2 and 4 (p=0.0019). In conclusion, our observational study suggests that zoledronic acid may stimulate bone apposition locally in the process of particle-induced osteolysis.

Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin.

Alterations of the key regulators of osteoclastogenesis, receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been implicated in wear particle-induced osteolysis, the most common cause for implant failure in total joint replacements. This study investigated the effect of exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 28 C57BL/6J mice randomized to four groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III and IV particles and subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until sacrifice. After 2 weeks, calvaria were prepared for histology and histomorphometry. Bone resorption was measured within the midline suture using Giemsa staining and osteoclast numbers were determined using TRAP staining. UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis and bone resorption. Both immediate and delayed treatment with OPG counteracted these particle-induced effects significantly, suppressing osteoclast formation and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion, exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine calvarial model. This important finding underscores the crucial significance of the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG may prove an effective treatment modality for wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.