Peri-implant Osteolysis Research Articles

Treatment of trapeziometacarpal osteoarthritis with a pyrocarbon implant: Long-term results

ObjectiveTrapeziometacarpal osteoarthritis is the second most common degenerative articular disease. Although initial therapy should be conservative, surgical treatment is often required. Several surgical techniques have been described, but none has proved to be a gold-standard. The objective of this study was to evaluate the long-term clinical and radiological results of trapeziometacarpal interposition arthroplasty with the PyroDisk implant (Integra LifeSciences). MethodsA retrospective long-term study of all patients who underwent trapeziometacarpal interposition arthroplasty with a pyrocarbon implant at our institution was performed. ResultsTwenty-four patients who underwent PyroDisk (Integra LifeSciences). arthroplasty at our institution were identified; 7 were lost to follow-up; 17 patients were evaluated, for 20 arthroplasties. Mean follow-up was 13.5 years (range: 12–15 years). Disability in daily living activities was low (mean Disabilities of the Arm, Shoulder and Hand score, 29.6), with a mean pain score of 0.22. Mean Kapandji score at 13.5 years was 8.63. Mean grip strength was 18.5 kg and key-pinch strength 2.84 kg. Two patients had implant dislocation, needing revision surgery for implant removal. Implant survival rate was 88.9% at 13.5 years. ConclusionsOur study confirmed that good clinical results can be expected after interposition arthroplasty with PyroDisk (Integra LifeSciences). Regarding radiological findings, peri-implant osteolysis was present in 12 of the patients, but had no influence on the clinical outcome.

Caffeic acid phenethyl ester ameliorates titanium particle-induced bone loss and inflammatory reaction in a mouse acute model

With the increasing clinical application of dental and orthopedic implants, the problem of peri-implant osteolysis has attracted attention. The inflammatory response and osteoclast differentiation induced by wear particles play an important role in peri-implant bone loss. However, the treatment of peri-implant osteolysis is still lacking. In the present study, we investigated the effect of caffeic acid phenethyl ester (CAPE) on titanium particles induced bone loss in a mouse model. We found that CAPE significantly suppressed titanium particle-induced bone loss in vivo. CAPE treatment decreased ratio of nuclear factor kappa B receptor activator ligand (RANKL)/osteoprotegerin (OPG) and subsequently reduced osteoclastogenesis in the mouse model. In addition, CAPE downregulated the expression and secretion of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) stimulated by titanium particles in vivo. In summary, we conclude that CAPE prevent the titanium particles-induced bone loss.

The ceramic coated implant (CCI). Evolution total ankle replacements: a retrospective analysis of 40 ankles with 8 years follow-up.

Diminutive data is available on the outcome of several previously used total ankle replacement implants. The purpose of this study was to investigate the medium-term functional and radiological outcome and implant survival of the CCI Evolution implant. Consecutive series of 40 ankles operated in our hospital with primary TAR using the CCI Evolution implant in 2010-2013 were available for follow-up. The prospective clinical and radiographic data including the Kofoed score, subjective satisfaction and standard radiographs were collected preoperatively and at fixed time-points postoperatively. A CT was obtained in cases where osteolysis or loosening were suspected. The improvement of the Kofoed score and subjective satisfaction were statistically significant (p<0.0001). The implant survival was 97% (95% confidence interval (CI) 81%-100 %) at 5 years, and 81 % (95% confidence interval (CI) 60 %-92%) at 8 years. There were altogether 25 (64%) complications. Overall revision rate was 28% and failure rate 13%. The CCI implant outcome was not acceptable. The malposition of prosthetic components, subsidence, and peri-implant osteolysis were recorded often. Although the patient reported outcome measures improved, mostly due to positive changes in pain severity, overall revision and failure rates were high and comparable with previous findings of the CCI implant.

Total hip arthroplasty in the treatment of severe stages of osteonecrosis of the femoral head and osteoarthritis: results and complications

BACKGROUND: Nowadays total hip arthroplasty (THA) is the method of choice for the treatment of late stages osteonecrosis of the femoral head (OFH) and osteoarthritis (OA) of the hip joint.&#x0D; OBJECTIVE: To evaluate the efficacy and complication pattern of THA in late stages of OFH and OA.&#x0D; MATERIALS AND METHODS: The study included 74 patients who underwent primary THA for OA stages IIIIV (Kellgren and Lawrence classification) and for OFH stages IIIIV (ARCO classification). Group 1 included 34 patients with OFH stages IIIIV, and group 2 40 patients with OA stages IIIIV. The groups were comparable by gender and age. All patients underwent implantation of endoprosthesis components using press-fit fixation with a metalpolyethylene articulation. Treatment results were assessed with regard to the incidence of complications and functional results at 3, 6 months, 1 and 3 years after THA.&#x0D; RESULTS: In our study, the survival rate of components after THA within 3 years after implantation was 100%. No cases of periprosthetic fracture, periprosthetic infection, and aseptic instability of endoprosthesis components were observed in both groups. The surface inflammation of the postoperative wound was detected in 1 (2.9%) patient in the OFH group and in 1 (2.5%) patient in OA group. Dislocation of the endoprosthesis occurred in 1 patient with OFH; there were no such findings in the OA group. The frequency of peri-implant osteolysis was twice lower (2.5%) in patients with OA compared to OFH group (5.8%). There were no statistically significant differences in the functional results dynamics before and after surgery between the groups (Harris score). The average Harris scale score in patients with OFH was 63 and reached 94 after 3 years; in OA group 58 and 94, respectively.&#x0D; CONCLUSION: THA is an alternative method in the treatment of severe hip arthroplasty. Endoprosthetics using a cementless endoprosthesis with a metalpolyethylene articulation demonstrated high efficacy as well as a low number of complications among patients with OFH and OA. We found no significant difference in THA results in terms of survival, postoperative complications, and functional outcome in patients with OFH and OA. Longer postoperative follow-up is advisable, which may allow us to establish some differences in treatment outcomes.

The Role of the Innate Immune System in Wear Debris-Induced Inflammatory Peri-Implant Osteolysis in Total Joint Arthroplasty.

Periprosthetic osteolysis remains a leading complication of total hip and knee arthroplasty, often resulting in aseptic loosening of the implant and necessitating revision surgery. Wear-induced particulate debris is the main cause initiating this destructive process. The purpose of this article is to review recent advances in understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease. A strong activator of the peri-implant innate immune this debris-induced inflammatory cascade is dictated by macrophage secretion of TNF-α, IL-1, IL-6, and IL-8, and PGE2, leading to peri-implant bone resorption through activation of osteoclasts and inhibition of osteoblasts through several mechanisms, including the RANK/RANKL/OPG pathway. Therapeutic agents against proinflammatory mediators, such as those targeting tumor necrosis factor (TNF), osteoclasts, and sclerostin, have shown promise in reducing peri-implant osteolysis in vitro and in vivo; however, radiographic changes and clinical diagnosis often lag considerably behind the initiation of osteolysis, making timely treatment difficult. Considerable efforts are underway to develop such diagnostic tools, therapies, and identify novel targets for therapeutic intervention.

KNEE PERIPROSTHETIC FRACTURES IN THE ELDERLY: CURRENT CONCEPT.

Periprosthetic fractures around total knee arthroplasty in elderly represent an emerging cause of implant revision and their incidence seems destined to further increase in the upcoming years, considering the ever-increasing number of implanted prostheses. These are complex injuries with very high complication rates. It has been estimated that the incidence of femoral periprosthetic fractures after T.K.A. ranged between 0,3 to 2,5%, but increases up to 38% when considering revision T.K.A. Patient-related risk factors for T.K.A. periprosthetic fracture (T.K.A.P.F.) include osteoporosis, age, female sex, revision arthroplasty and peri-implant osteolysis. The grate debate concerns the choice of the most appropriate fixation device for T.K.A.P.F.: closed or open reduction with internal fixation with either locked plate or intramedullary nail is the most commonly used for treating these fractures. Success of these methods depends on the fracture pattern, the stability of implants, and the patient's bone quality which is often poor in elderly, thus resulting in high complication rates. Conversely, a revision of T.K.A. (R.T.K.A.) should be considered in case of prosthetic component instability, severe comminution or metaphyseal extension of the fracture (that precludes a good fixation), previous treatments failure and severe malalignment of T.K.A. Instead megaprosthesis and allograft-prosthesis composite are necessary in case of sever bone loss. Considering the variability of the clinical scenario of T.K.A.P.F., this complex injury requires and experienced and comprehensive approach based on both facture fixation and/or revision arthroplasty.

LIM Homeobox Transcription Factor 1-β Expression is Upregulated in Patients with Osteolysis after Total Ankle Arthroplasty and Inhibits Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Differentiation in Vitro.

BackgroundOsteolysis is one of the most common problems that occurs after total hip and knee arthroplasty and has recently become a significant problem after total ankle arthroplasty (TAA). In this study, we investigated the role of LIM homeobox transcription factor 1-β (Lmx1b) in osteoclast differentiation. By evaluating the expression profiles associated with osteolysis following TAA treatment, Lmx1b was found to be differentially expressed in patients with osteolysis after TAA.MethodsTo identify the important genes associated with osteolysis after TAA, RNA sequencing was performed by analyzing 8 patient samples: 5 primary TAA samples (control group) and 3 TAA samples revised for flexion instability (osteolysis group). By analyzing the differentially expressed genes and gene ontologies, Lmx1b expression was found to be upregulated in the osteolysis group compared to that in the control group. Focusing on the role of Lmx1b in bone cells, Lmx1b was overexpressed by a retrovirus in osteoclast precursor cells. The cultured cells were stained with tartrate-resistant acid phosphatase, and the expression of osteoclast-related genes was analyzed using real-time polymerase chain reaction.ResultsLmx1b overexpression in osteoclast precursors suppresses osteoclast formation and resorptive activity. The expression of osteoclast marker genes was significantly reduced during osteoclast differentiation by Lmx1b overexpression. Furthermore, Lmx1b is associated with nuclear factor of activated T cells 1 (NFATc1) and inhibited NFATc1 translocation into the nucleus.ConclusionsThese results provide novel insights into the anti-bone resorptive effect of Lmx1b on osteolysis after TAA and may lead to the development of effective preventative and therapeutic strategies for peri-implant osteolysis.

Efficacy of Bisphosphonate-Conjugated Sitafloxacin in a Murine Model of S. aureus Osteomyelitis: Evidence of "Target & Release" Kinetics and Killing of Bacteria Within Canaliculi.

S. aureus infection of bone is difficult to eradicate due to its ability to colonize the osteocyte-lacuno-canalicular network (OLCN), rendering it resistant to standard-of-care (SOC) antibiotics. To overcome this, we proposed two bone-targeted bisphosphonate-conjugated antibiotics (BCA): bisphosphonate-conjugated sitafloxacin (BCS) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS). Initial studies demonstrated that the BCA kills S. aureus in vitro. Here we demonstrate the in vivo efficacy of BCS and HBCS versus bisphosphonate, sitafloxacin, and vancomycin in mice with implant-associated osteomyelitis. Longitudinal bioluminescent imaging (BLI) confirmed the hypothesized “target and release”-type kinetics of BCS and HBCS. Micro-CT of the infected tibiae demonstrated that HBCS significantly inhibited peri-implant osteolysis versus placebo and free sitafloxacin (p < 0.05), which was not seen with the corresponding non-antibiotic-conjugated bisphosphonate control. TRAP-stained histology confirmed that HBCS significantly reduced peri-implant osteoclast numbers versus placebo and free sitafloxacin controls (p < 0.05). To confirm S. aureus killing, we compared the morphology of S. aureus autolysis within in vitro biofilm and infected tibiae via transmission electron microscopy (TEM). Live bacteria in vitro and in vivo presented as dense cocci ~1 μm in diameter. In vitro evidence of autolysis presented remnant cell walls of dead bacteria or “ghosts” and degenerating (non-dense) bacteria. These features of autolyzed bacteria were also present among the colonizing S. aureus within OLCN of infected tibiae from placebo-, vancomycin-, and sitafloxacin-treated mice, similar to placebo. However, most of the bacteria within OLCN of infected tibiae from BCA-treated mice were less dense and contained small vacuoles and holes >100 nm. Histomorphometry of the bacteria within the OLCN demonstrated that BCA significantly increased their diameter versus placebo and free antibiotic controls (p < 0.05). As these abnormal features are consistent with antibiotic-induced vacuolization, bacterial swelling, and necrotic phenotype, we interpret these findings to be the initial evidence of BCA-induced killing of S. aureus within the OLCN of infected bone. Collectively, these results support the bone targeting strategy of BCA to overcome the biodistribution limits of SOC antibiotics and warrant future studies to confirm the novel TEM phenotypes of bacteria within OLCN of S. aureus-infected bone of animals treated with BCS and HBCS.

Involvement of NF-κB/NLRP3 axis in the progression of aseptic loosening of total joint arthroplasties: a review of molecular mechanisms.

Particulate wear debris can trigger pro-inflammatory bone resorption and result in aseptic loosening. This complication remains major postoperative discomforts and complications for patients who underwent total joint arthroplasty. Recent studies have indicated that wear debris-induced aseptic loosening is associated with the overproduction of pro-inflammatory cytokines. The activation of osteoclasts as a result of inflammatory responses is associated with osteolysis. Moreover, stimulation of inflammatory signaling pathways such as the NF-κB/NLRP3 axis results in the production of pro-inflammatory cytokines. In this review, we first summarized the potential inflammatory mechanisms of wear particle-induced peri-implant osteolysis. Then, the therapeutic approaches, e.g., biological inhibitors, herbal products, and stem cells or their derivatives, with the ability to suppress the inflammatory responses, mainly NF-κB/NLRP3 signaling pathways, were discussed. Based on the results, activation of macrophages following inflammatory stimuli, overproduction of pro-inflammatory cytokines, and subsequent differentiation of osteoclasts in the presence of wear particles lead to bone resorption. The activation of NF-κB/NLRP3 signaling pathways within the macrophages stimulates the production of pro-inflammatory cytokines, e.g., IL-1β, IL-6, and TNF-α. According to in vitro and in vivo studies, novel therapeutics significantly promoted osteogenesis, suppressed osteoclastogenesis, and diminished particle-mediated bone resorption. Conclusively, these findings offer that suppressing pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome represents a novel approach to attenuate wear-particle-related osteolytic diseases.

Enteropathogenic Escherichia coli Mediates CoCrMo Particle-Induced Peri-Implant Osteolysis by Increasing Peripheral 5-HT.

The human gut microbiota has been proven to have great effects on the regulation of bone health. However, the association between gut microbiota and particle-induced osteolysis, which is the primary cause of aseptic loosening, is still unknown. In this study, we used a combination of wide-spectrum antibiotics to eliminate the majority of gut microbiota and found that reduction of gut commensal bacteria significantly alleviated the progression of osteolysis, in which anaerobe was the biggest culprit in the exacerbation of osteolysis. Furthermore, colonization of enteropathogenic Escherichia coli (EPEC), a subspecies of anaerobe, could promote the development of particle-induced osteolysis by increasing the secretion of peripheral 5-hydroxytryptamine (5-HT) from the colon. Elevated 5-HT level decreased the phosphorylation of CREB and inhibited the proliferation of osteoblasts. Collectively, these results indicated EPEC colonization suppressed the bone formation and aggravated particle-induced osteolysis in vivo. Thus, clearance of EPEC is expected to become a potential preventive approach to treat debris-induced osteolysis and aseptic loosening.

Анализ вероятности возникновения периимплантной инфекции и ее последствия при внешней транспедикулярной фиксации позвоночника

The main purpose of spinal fixation is to provide conditions for vertebral fusion at the level of injury. Bone fusion is associated with many factors including stability of injured segment, restoration of the anterior support column, condition of the bone tissue and other aspects. The timing of bone formation can be affected by soft tissue inflammation at the site of the rods of the external fixation system. Peri-implant infection is reported to occur in 0.7-20 % of cases with external transpedicular fixation. The timing of the complication and the dependence of the frequency of the occurrence on the patient's treatment strategy are debatable. Another topical issue is the study of the consequences of peri-implant infection with the need to establish the validity of the assumption about the effect of peri-implant infection on the rate of bone formation using a clinical model. This would allow the findings to be used for new methods of treatment considering the risk of possible complications, giving preference to low-traumatic semi-closed methods of spine fixation. Nevertheless, external transpedicular fixation is practical for open spinal injury or significant vertebral displacement with the need of significant reduction efforts to be applied. The purpose was to explore the effect of soft tissue inflammation on the timing of bone formation with spinal fusion surgery using different surgical methods of treatment of uncomplicated spinal fractures. Material and methods The review included 111 patients with uncomplicated fractures of the lower thoracic and lumbar spine. Based on a retrospective analysis the participants were assigned to three groups depending on the presence/absence of peri-implant infection and the timing of the occurrence: 81 patients experienced no complications, 16 had serous-purulent inflammation of soft tissues at the site of the rods of the external fixation device that developed on average after 20 days with 14 patients seen with pin tract infection after 2 months of anterior fusion surgery and failed bone formation. Results Peri-implant infection rate was found to be higher with external fixation (14.4 %) than that with anterior fusion surgery (12.6 %). The complication rate was 1.85 times less with one-stage surgical treatment as compared to two-stage treatment. Peri-implant infection developed later (after 21‑63 days) with one-stage treatment as compared with two-stage procedure (after 12-24 days). Infection associated with the external fixation led to increase in timing of bone formation by 6-7 %, by 2-4 weeks on average. Bone formation failed in 35 % of cases (p &lt; 0.0002) due to peri-implant inflammation caused by Staphylococcus aureus, as the common pathogen and the bacteria detected resulted in ineffective antibacterial therapy. Immunological parameters (IgM and haptoglobin) were quantified to assess the risk of peri-implant infection. Discussion Peri-implant infection rate associated with external transpedicular fixation was shown to be comparable with the previously obtained data. Sharply defined notions were reported earlier to differentiate between infectious peri-implant osteolysis and mechanical loosening. We compared the data on the duration of bone formation and the timing of peri-implant infection and developed a model that with high sensitivity (73 %) and specificity (100 %) allowed description of cases with impaired osteogenesis. Changes in some immunological parameters (immunoglobulins, acute-phase proteins) were shown to affect both bone formation and stability of bone fixation.

Titanium surface with nanospikes tunes macrophage polarization to produce inhibitory factors for osteoclastogenesis through nanotopographic cues

Definitive prevention of inflammatory osteolysis around peri-implant bone tissue remains unestablished. M1 macrophages play a key role in the host defense against inflammatory osteolysis, and their polarization depends on cell shape. Macrophage polarization is controlled by environmental stimuli, particularly physicochemical cues and hence titanium nanosurface might tune macrophage polarization and function. This study determined whether titanium nanosurfaces with anisotropically patterned nanospikes regulates macrophage polarization for inhibiting osteoclast differentiation of osteoclast precursors. Alkaline-etching treatment with different protocols created two types of titanium nanosurfaces that had anisotropically patterned nanospikes with high or low distribution density, together with superhydrophilicity and the presence of hydroxyl groups. J774A.1 cells (mouse macrophage-like cell line), cultured on both titanium nanosurfaces, exhibited truly circulated shapes and highly expressed M1, but less M2, markers, without loss of viability. M1-like polarization of macrophages on both titanium nanosurfaces was independent of protein-mediated ligand stimulation or titanium surface hydrophilic or chemical status. In contrast, other smooth or micro-roughened titanium surfaces with little or no nanospikes did not activate macrophages under any culture conditions. Macrophage culture supernatants on both titanium nanosurfaces inhibited osteoclast differentiation of RAW264.7 cells (mouse osteoclast precursor cell line), even when co-incubated with osteoclast differentiation factors. The inhibitory effects on osteoclast differentiation tended to be higher in macrophages cultured on titanium nanosurfaces with denser nanospikes. These results showed that titanium nanosurfaces with anisotropically patterned nanospikes tune macrophage polarization for inhibiting osteoclast differentiation of osteoclast precursors, with nanotopographic cues rather than other physicochemical properties. Statement of significancePeri-implant inflammatory osteolysis is one of the serious issues for dental and orthopedic implants. Macrophage polarization and function are key for prevention of peri-implant inflammatory osteolysis. Macrophage polarization can be regulated by the biomaterial's surface physicochemical properties such as hydrophilicity or topography. However, there was no titanium surface modification to prevent inflammatory osteolysis through immunomodulation. The present study showed for the first time that the titanium nanosurfaces with anisotropically patterned nanospikes, created by the simple alkali-etching treatment polarized macrophages into M1-like type producing the inhibitory factor on osteoclast differentiation. This phenomenon attributed to nanotopographic cues, but not hydrophilicity on the titanium nanosurfaces. This nanotechnology might pave the way to develop the smart implant surface preventing peri-implant inflammatory osteolysis through immunomodulation.

Short-Term Complications and Outcomes of the Cadence Total Ankle Arthroplasty.

Total ankle arthroplasty (TAA) is an increasingly popular option for the operative treatment of ankle arthritis. The Cadence TAA entered clinical use in 2016 and was designed to address common failure modes of prior systems. We report early complications and radiographic and clinical outcomes of this total ankle system at a minimum of 2 years of follow-up. We performed a retrospective review of a consecutive cohort of patients undergoing primary Cadence TAA by a single surgeon from 2016 to 2017. Complications and reoperations were documented using the American Orthopaedic Foot & Ankle Society (AOFAS) TAA reoperation coding system. Patients completed the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) and Sport subscales, SF-12 Mental (MCS) and Physical (PCS) Component Summaries, and visual analog scale (VAS) pain rating (0-100). Radiographic evaluation was performed to assess postoperative range of motion (ROM) of the sole of the foot relative to the long axis of the tibia, alignment, and implant complications. Fifty-eight patients with a mean age of 63.3 years and mean body mass index of 31.9 kg/m2 were included. Twelve of 58 patients (20.7%) underwent an additional procedure(s) within 2 years, including 3 (5.2%) who required removal of one or both components, 2 for infection and 1 for osteolysis. Forty-three patients were followed for a minimum of 2 years with radiographic imaging; 1 patient's (2.3%) radiographs had signs of peri-implant osteolysis, with no cases demonstrating loosening or subsidence. FAAM-ADL, FAAM-Sport, SF-12 PCS, and VAS pain scores all improved at a mean of 27.4 months postoperatively, with mean score changes (± SD) of 16.3 (± 22.0), 25.3 (± 24.5), 6.0 (± 11.1), and -32.3 (± 39.8), respectively. Radiographic analysis revealed that average coronal alignment improved from 6.9 degrees from neutral preoperatively to 2.3 degrees postoperatively. The average ROM of the foot relative to the tibia was 36.5 degrees total arc of motion based on lateral radiographs. Early experience with this 2-component total ankle replacement was associated with a high component retention rate, improved coronal plane alignment, good postoperative ROM, radiographically stable implants, and improved patient function. Level IV, case series.

Staphylococcus aureus Cell Wall Biosynthesis Modulates Bone Invasion and Osteomyelitis Pathogenesis.

Staphylococcus aureus invasion of the osteocyte lacuno-canalicular network (OLCN) is a novel mechanism of bacterial persistence and immune evasion in chronic osteomyelitis. Previous work highlighted S. aureus cell wall transpeptidase, penicillin binding protein 4 (PBP4), and surface adhesin, S. aureus surface protein C (SasC), as critical factors for bacterial deformation and propagation through nanopores in vitro, representative of the confined canaliculi in vivo. Given these findings, we hypothesized that cell wall synthesis machinery and surface adhesins enable durotaxis- and haptotaxis-guided invasion of the OLCN, respectively. Here, we investigated select S. aureus cell wall synthesis mutants (Δpbp3, Δatl, and ΔmreC) and surface adhesin mutants (ΔclfA and ΔsasC) for nanopore propagation in vitro and osteomyelitis pathogenesis in vivo. In vitro evaluation in the microfluidic silicon membrane-canalicular array (μSiM-CA) showed pbp3, atl, clfA, and sasC deletion reduced nanopore propagation. Using a murine model for implant-associated osteomyelitis, S. aureus cell wall synthesis proteins were found to be key modulators of S. aureus osteomyelitis pathogenesis, while surface adhesins had minimal effects. Specifically, deletion of pbp3 and atl decreased septic implant loosening and S. aureus abscess formation in the medullary cavity, while deletion of surface adhesins showed no significant differences. Further, peri-implant osteolysis, osteoclast activity, and receptor activator of nuclear factor kappa-B ligand (RANKL) production were decreased following pbp3 deletion. Most notably, transmission electron microscopy (TEM) imaging of infected bone showed that pbp3 was the only gene herein associated with decreased submicron invasion of canaliculi in vivo. Together, these results demonstrate that S. aureus cell wall synthesis enzymes are critical for OLCN invasion and osteomyelitis pathogenesis in vivo.

Low Rate of Peri-implant Osteolysis in Trabecular Metal Total Ankle Replacement on Short- to Midterm Follow-up.

Peri-implant osteolysis is one of the major complications related to total ankle replacement. The aim of this study was to investigate the short- to midterm incidence of peri-implant osteolysis using computed tomography (CT) as imaging method for the Trabecular Metal Total Ankle (TMTA) implant representing a novel total ankle replacement (TAR) implant design regarding material and surgical technique. In total, 104 consecutive patients who had a primary TMTA replacement between March 2013 and October 2017 were included in the study. The radiographic evaluation included weightbearing anteroposterior and lateral views at baseline and after 3, 6, and every 12 months postoperatively. A helical CT was undertaken preoperatively and of the 80 patients available to follow up at least 12 months postoperatively, with average time interval between the TAR operation and the latest CT of 39 (range, 12-85) months. Eight of 80 patients had altogether 11 osteolytic lesions around the components on CT images. Seven lesions were found in tibia, 3 in talus, and 1 in distal fibula. Four of the tibial lesions were situated in the medial malleolus and were not in contact with the prosthesis component. The sizes of the osteolytic lesions ranged between 7 and 20 mm, and the average volume of the lesions was 689 mm3. We conclude that the risk of peri-implant osteolysis with the TMTA implant is minimal in short to midterm. The anatomic configuration, unique material, and surgical technique may all contribute to the TMTA implant having a low rate of peri-implant osteolysis. Level IV, case series.

Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway.

Peri-implant osteolysis (PIO) and the subsequent aseptic loosening are the main reasons for artificial joint implant failure. Existing methods for treating aseptic loosening are far from satisfactory, necessitating advanced drug exploration. This study is aimed at investigating the effect and underlying mechanism of tetrandrine (Tet) on inflammatory osteolysis. We established a Ti particle-induced inflammatory osteolysis mouse model and administered Tet or an equal volume of phosphate-buffered saline (PBS). Two weeks later, specimens were collected. Histological staining showed that Tet administration inhibited Ti-stimulated osteolysis. Tartrate-resistant acid phosphate (TRAP) staining and transmission electron microscopy (TEM) demonstrated that osteoclast formation was remarkably inhibited in the groups treated with Tet in a dose-dependent manner. In addition, relevant inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) were also significantly reduced in the calvaria of the Tet-treated groups. Exposure of receptor activator for nuclear factor-κB ligand- (RANKL-) induced bone marrow-derived macrophages (BMMs) and RAW264.7 cells to Tet significantly reduced osteoclast formation, F-actin ring formation, bone resorption, and the expression of relevant genes (matrix metallopeptidase 9 (MMP-9), TRAP, and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1)) during osteoclastogenesis in vitro. Mechanistic studies using Western blotting demonstrated that Tet inhibited the nuclear factor (NF)-κB signaling pathway by decreasing the phosphorylation of inhibitor of NF-κB α (IκBα) and p65, which play important roles in osteoclast formation. Collectively, our data indicate that Tet suppressed Ti-induced inflammatory osteolysis and osteoclast formation in mice, suggesting that Tet has the potential to be developed to treat and prevent wear particle-induced inflammatory osteolysis.

Periimplant osteolysis does not affect the outcome of rotator cuff repair: a systematic review and meta-analysis.

The goal of this study was to perform a systematic review and meta-analysis to compare the clinical and radiologic outcomes of rotator cuff repair, depending on the presence of developed periimplant osteolysis (PIO) after using suture anchors. The electronic databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for articles published up until October 2019 to find relevant articles comparing the outcomes of rotator cuff repair between the periimplant osteolysis group and non-periimplant osteolysis group. Data searching, extraction, analysis, and quality assessment were performed according to the Cochrane Collaboration guidelines. The results are presented as risk ratio (RR) for binary outcomes and standardised mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). Six clinical studies were included. No significant differences were found between the group with periimplant osteolysis and the group without periimplant osteolysis regarding retear rate (RR = 1.34; 95% CI 0.93-1.94; I2 = 28%), postoperative clinical scores (SMD = 0.29; 95% CI - 0.26 to 0.83; I2 = 80%) and range of motion (ROM); forward flexion (SMD = 0.39; 95% CI - 0.16 to 0.93; I2 = 0%), external rotation (SMD = - 0.10; 95% CI - 0.64 to 0.45; I2 = 0%) and internal rotation (SMD = - 0.37; 95% CI - 0.92 to 0.17; I2 = 0%). The presence of periimplant osteolysis after rotator cuff repair with suture anchor does not affect the clinical outcomes such as retear rate, clinical scoring, and ROM. However, as there was no standard consensus on the criteria for evaluating periimplant osteolysis, this result may not fully reflect the effect of periimplant osteolysis depending on its severity. Level IV.

A Retrospective Analysis of Results and Outcomes after Cadence Total Ankle Arthroplasty Implanted through the End of 2017

Category:Ankle; Ankle ArthritisIntroduction/Purpose:Total ankle arthroplasty (TAA) is an increasingly popular operative treatment of ankle arthritis, due to its ability to decrease adjacent joint degeneration and preserve gait mechanics compared to ankle arthrodesis. However, ankle arthroplasty components have a shorter mean longevity then their hip, knee, or shoulder counterparts. The Cadence TAA entered clinical use in 2016 and was designed to address common failure modes of prior systems. We report here on radiographic and clinical outcomes and early complications of the Cadence TAA system at a minimum of 2 years follow-up.Methods:Patients who underwent primary Cadence TAA from 2016 through 2017 by one fellowship-trained foot and ankle surgeon were eligible. Exclusion criteria included prior ipsilateral ankle arthrodesis or arthroplasty and lack of followup. Chart review was performed for eligible patients to identify complications and reoperations. Patients were contacted to obtain Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) and Sport subscores, SF-12 Mental (MCS) and Physical Health (PCS) subscores, and Visual Analog Scale (VAS) pain levels (rated 0-100). Scores were analyzed with 2-sided repeated measures T- tests, with P<0.05 as significant. A second, blinded, fellowship-trained foot and ankle surgeon evaluated followup 5-view radiographs of each ankle to measure range of motion (ROM), alignment, peri-implant osteolysis, and component loosening or subsidence. Subsidence or loosening were defined, respectively, as >2mm or >2⁰ change in position for the tibial component and>5mm or >5⁰ change for the talar component.Results:Sixty patients were included with mean age 64 and mean BMI 32.0. Thirty patients (50%) had concurrent other procedure(s). FAAM-ADL, FAAM-Sports, SF-12 PCS, and VAS pain scores all improved significantly at mean 2.24 years post-op (Table 1). Ten patients (6.7%) had operative complications requiring 15 surgeries (mean 265 days to first reoperation). Three patients (5%) required removal of one or both components, for 2-year implant survival of 95.0%. Two revisions were for infection and one for osteolysis. This produced a mechanical failure rate of 1/60 (1.7%). Radiographic analysis revealed average coronal alignment improved from 7.4⁰ from neutral preoperatively to 2.2⁰ postoperatively. Average ROM was 36.5⁰ total arc of motion.One of 38 (2.6%) had signs of peri-implant osteolysis, with no cases demonstrating loosening or subsidence.Conclusion:Two-year follow-up of the Cadence TAA system demonstrates mechanically stable implants resulting in improved patient function and preserved ankle range of motion. Outcomes compare favorably to those of other TAA systems at 2-year follow-up. Further radiographic and clinical follow-up are needed to evaluate implant longevity and long-term patient functional outcomes.

Dual directions to address the problem of aseptic loosening via electrospun PLGA @ aspirin nanofiber coatings on titanium

Peri-implant aseptic inflammation and osteolysis can cause aseptic loosening, leading to the failure of implants. Therefore, aseptic loosening of orthopedic implants remains an imminent problem for the development of durable and effective implants. In this work, a common anti-inflammatory drug (aspirin, ASA) was loaded in poly(lactic-co-glycolic acid) (PLGA) to construct nanofiber coatings on titanium (Ti) via electrospinning. The adhesion of the nanofiber coatings to Ti was ensured by polydopamine (PDA) modification. A stable and sustainable release of aspirin from the nanofiber coatings could last up to 60 days. Such electrospun PLGA@ASA nanofiber coatings could promote proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) as well as inhibit M1 polarization and RANKL-induced osteoclast differentiation of macrophages in vitro. These results indicated that this facile formulation of the PLGA@ASA nanofiber coatings for long-term drug release could be expected to address the problem of aseptic loosening effectively in dual directions of both anti-inflammation and improving osseointegration simultaneously. Notably, the in vivo experiments demonstrated that PLGA@ASA nanofiber coatings did promote osseointegration ability of Ti implants significantly, even in challenging condition with wear particles, and also effectively inhibited Ti particle induced osteolysis around the implants. This work indicates a promising way for the development of durable and effective implants by using PLGA@ASA-PDA-Ti to address the problem of aseptic loosening in dual directions.

Magnoflorine Suppresses MAPK and NF-κB Signaling to Prevent Inflammatory Osteolysis Induced by Titanium Particles In Vivo and Osteoclastogenesis via RANKL In Vitro.

Wear particles that detach from the surface of prostheses induce excessive activation of osteoclast and immoderate release of inflammatory cytokines that lead to peri-implant osteolysis and aseptic loosening. In this work, we investigated whether magnoflorine, a quaternary aporphine alkaloid extracted from the Chinese herb Magnolia or Aristolochia, could effectively inhibit inflammatory calvarial osteolysis caused by titanium particles in mouse models, inflammatory response as well as osteoclastogenesis in vitro mediated via receptor activator of NF-κB ligand (RANKL). Micro-computed tomography and histological examination of mice treated with magnoflorine revealed fewer resorption pits, less osteoclasts formation and inflammatory cytokine expression. Moreover, in vitro differentiation of osteoclasts and bone resorption as well as titanium particle-induced inflammatory response were dose-dependently inhibited by magnoflorine. These were accompanied by reduced transcription of osteoclast-specific genes encoding tartrate-resistant acid phosphatase (TRAP), V-ATPase d2, c-Fos, cathepsin K, nuclear factor of activated T cells (NFAT) c1, and calcitonin receptor (CTR). Further research on mechanism showed that the inhibition of phosphorylation of TAK1 and subsequent activation of MAPK and NF-κB signaling pathways were found to mediate the suppressive effects of magnoflorine. Collectively, these results suggested that magnoflorine treatment could effectively prevent peri-implant osteolysis due to wear debris as well as other diseases caused by chronic inflammation and excessive osteoclast activation.