Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence

In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.

Antibiotic-free antimicrobial poly (methyl methacrylate) bone cements:A state-of-the-art review

Prosthetic joint infection(PJI)is the most serious complication following total joint arthroplasty,this being because it is associated with,among other things,high morbidity and low quality of life,is difficult to prevent,and is very challenging to treat/manage.The many shortcomings of antibiotic-loaded poly(methyl methacrylate)(PMMA)bone cement(ALBC)as an agent for preventing and treating/managing PJI are well-known.One is that microorganisms responsible for most PJI cases,such as methicillin-resistant S.aureus,have developed or are developing resistance to gentamicin sulfate,which is the antibiotic in the vast majority of approved ALBC brands.This has led to many research efforts to develop cements that do not contain gentamicin(or,for that matter,any antibiotic)but demonstrate excellent antimicrobial efficacy.There is a sizeable body of literature on these socalled“antibiotic-free antimicrobial”PMMA bone cements(AFAMBCs).The present work is a comprehensive and critical review of this body.In addition to summaries of key trends in results of characterization studies of AFAMBCs,the attractive features and shortcomings of the literature are highlighted.Shortcomings provide motivation for future work,with some ideas being formulation of a new generation of AFAMBCs by,example,adding a nanostructured material and/or an extract from a natural product to the powder and/or liquid of the basis cement,respectively.

Influences of IL-6R Antibody on PMMA Bone Cement-mediated Expression of OPG and RANKL in Synovial Fibroblasts

Effect of interleukin-6 receptor （IL-6R） antibody on polymethyl methacrylate （PMMA） bone cement-mediated expression of osteoprotegerin （OPG） and ：receptor activator of nuclear fac- tor-kappaB ligand （RANKL） in synovial fibroblasts was investigated. Synovial tissue obtained from to- tal knee arthroplasty was digested and cultured. Inverted microscope was employed to observe the synovial cells and immunocytochemistry （SABC method） staining was used to identify synovial fibro- blasts. This experiment was divided into three groups according to different culture media： PMMA group （75μg/mL PMMA bone cement particles）, IL-6R antibody group （10 ng/mL IL-6R antibody＋75 μg/mL PMMA bone cement particles）, and control group （no IL-6R antibody or PMMA bone cement particles）. Influence of IL-6R antibody and PMMA on proliferation of synovial fibroblasts was meas- ured by cell counting kit-8 （CCK-8）. ELISA method was used to measure OPG and RANKL levels in culture solution. Fluorescence quantitative real-time PCR （FQ-PCR） was used to detect the expression of OPG and RANKL mRNA. After three consecutive passages, more than 95% of the primary synovial cells became long spindle fibroblast-like cells. SABC staining results showed that the fibroblast-like cells were negative for anti-CD68 antibody and positive for anti-vimentin antibody, with brown madder stained. CCK-8 test demonstrated that the absorbance （A） value at 450 nm was significantly lower in IL-6R antibody group than in PMMA group and control group （P〈0.01）, but there was no statistically significant difference in A value at 450 nm between the control group and PMMA group （P〉0.05）. Re- suits of ELISA indicated that the expression of OPG was significantly higher in IL-6R antibody group than in PMMA group and control group （P〈0.01）. The expression of RANKL was inhibited （P〈0.05）, and the ratio of OPG/RANKL was significantly increased in IL-6R antibody group as compared with PMMA group and control group. There was no significant difference in the expression of OPG between control group and PMMA group （P〉0.05）, but the expression of RANKL was higher in PMMA group than in control group （P〈0.05）, and there was a significant difference in the ratio of OPG/RANKL be- tween them （P〈0.05）. Results of FQ-PCR revealed the expression of RANKL mRNA was significantly inhibited （P〈0.01） and the expression of OPG mRNA was significantly increased （P〈0.01） in IL-6R an- tibody group as compared with PMMA group and control group. The expression of RANKL mRNA was higher in PMMA group than in control group （P〈0.05）, but the expression of OPG mRNA had no sig- nificant difference between them （P〉0.05）. IL-6R antibody could significantly increase the expression of OPC~ but inhibit the expression of RANKL, which might provide a theoretical basis of molecular bi- ology for the prevention and treatment of aseptic loosening of prosthesis.

Synthesis of Chitosan-Hydroxyapatite Composites and Its Effect on the Properties of Bioglass Bone Cement

Chitosan-hydroxyapatite （CS-HA） composite powders were synthesized via in situ co-precipitation method, through the reaction of Ca（NO3）2 and H3PO4 in the simulated body fluid （SBF） containing appropri- ate amount of chitosan. The thermal evolution, microstructure and morphology were studied by TG-DTA （thermogravimetry-differential thermal analysis）, XRD （X-ray diffraction）, FTIR （Fourier transform infrared spectroscopy） and TEM （transmission electron microscopy）. The in vitro bioactivity test showed that the obtained CS-HA composites had higher capability of inducing calcium ions deposition. Effects of CS-HA com- posites on the bioactivity and compressive strength of bioglass bone cement were investigated. The results indicated that the bioactivity of bioglass bone cement could be improved further when CS-HA composite pow- ders were added into the cement, and appropriate amount of CS-HA additive was favorable for compressive strength improvement of bioglass bone cement.

Treatment of Kümmell’s disease with sequential infusion of bone cement:A retrospective study

BACKGROUND Percutaneous vertebroplasty(PVP)is an effective method for the treatment of neurologically intact Kümmell’s disease,but bone cement leakage during surgery is a problem that deserves attention.AIM To reduce bone cement leakage and evaluate the effect of the sequential infusion of bone cement during PVP for the treatment of stage I or II Kümmell’s disease.METHODS Patients with Kümmell’s disease treated in our hospital from September 2015 to September 2018 were retrospectively analyzed.Patients meeting the inclusion and exclusion criteria were divided into two groups:Traditional single infusion and sequential infusion(SI).The visual analog scale(VAS)and Oswestry disability index(ODI)were evaluated and compared,and duration of operation,bone cement content and complications were recorded.RESULTS Forty-five patients were included in this study;there were 24 in the traditional single infusion group and 21 in the SI group.The VAS and ODI were significantly different for both groups when compared pre-and postoperatively,whereas the differences between 1 wk postoperatively and at the final follow-up were not statistically.When the VAS and ODI of the two groups were compared,there were no significant differences at any time point.The leakage rate of bone cement was significantly lower in the SI group(14.3%,3 of 21)than that in the traditional single infusion group(41.7%,10 of 24).CONCLUSION SI in unipedicular PVP is a safe and effective procedure for neurologically intact Kümmell’s disease,and this technique could decrease the incidence of bone cement leakage.

Injectable bioactive polymethyl methacrylate-hydrogel hybrid bone cement loaded with BMP-2 to improve osteogenesis for percutaneous vertebroplasty and kyphoplasty

Poly methyl methacrylate(PMMA)bone cement is used in augmenting and stabilizing fractured vertebral bodies through percutaneous vertebroplasty(PVP)and percutaneous kyphoplasty(PKP).However,applications of PMMA bone cement are limited by the high elasticity modulus of PMMA,its low biodegradability,and its limited ability to regenerate bone.To improve PMMA bio activity and biodegradability and to modify its elasticity modulus,we mixed PMMA bone cement with oxidized hyaluronic acid and carboxymethyl chitosan in situ cross-linking hydrogel loaded with bone morphogenetic protein-2(BMP-2)to achieve novel hybrid cement.These fabric ated PMMA-hydrogel hybrid cements exhibited lower setting temperatures,a lower elasticity modulus,and better biodegradability and biocompatibility than that of pure PMMA cement,while retaining acceptable setting times,mechanical strength,and inj ectability.In addition,we detected release of BMP-2 from the PMMA-hydrogel hybrid cements,significantly enhancing in vitro osteogenesis of bone marrow mesenchymal stem cells by up-regulating the gene expression of Runx2,Coll,and OPN.Use of PMMA-hydrogel hybrid cements loaded with BMP-2 on rabbit femoral condyle bone-defect models revealed their biodegradability and enhanced bone formation.Our study demonstrated the favorable mechanical properties,biocompatibility,and biodegradability of fabricated PMMA-hydrogel hybrid cements loaded with BMP-2,as well as their ability to improve osteogenesis,making them a promising material for use in PKP and PVP.

Bone cement implantation syndrome during hip replacement in a patient with pemphigus and Parkinson’s disease: A case report

BACKGROUND Bone cement implantation syndrome(BCIS)is characterized by hypotension,arrhythmia,diffuse pulmonary microvascular embolism,shock,cardiac arrest,any combination of these factors,or even death following bone cement implantation.CASE SUMMARY An 80-year-old patient with pemphigus and Parkinson’s disease underwent total hip replacement under spinal subarachnoid block and developed acute pulmonary embolism after bone cement implantation.The patient received mask mechanical ventilation with a continuous intravenous infusion of adrenaline(2μg/mL)at a rate of 30 mL/h.Subsequently,the symptoms of BCIS were markedly alleviated,and the infusion rate of adrenaline was gradually reduced until the infusion was completely stopped 45 min later.The patient was then transferred to the Department of Orthopedics,and anticoagulation therapy began at 12 h postoperatively.No other complications were observed.CONCLUSION This is a rare case of BCIS in a high-risk patient with pemphigus and Parkinson’s disease.

Drug Release Characteristics of Hydroxyapatite Bone Cement

To discuss the feasibility of bydroxyapatite bone cement （HAC） used as a drug delivery carrier and observe the bacteriostatic activity of HAC/ Norvancomycin（ HAC/ NVCM ） composite in vitro and its release characteristics in vivo. Bacteriostatic zone and cycle of composite containing 1.5wt% of NVCM were measured in vitro studies. In vivo stndies , the composite was implanted into the top of rabbit＇ s tibia as the local medication group, HAC without NVCM being composed was also implanted and NVCM was injected into auricular vein as the systemic medication group. Cnncentrations of NVCM in blood and local bone were measured in both groups at different time points. The experimental results showed that HAC did not influence the bacteriostatic activity of NVCM otviously, and NVCM exist in the porosities of HAC in the pattern of amorphism. The blood coueemrations of NVCM in local medication group were always lower than those in systemic medication group at any time point, while the bone concentrations of NVCM in local medication group were much higher than those of systemic medication group,which remained to be 3.96μg/mg/mL after 2 weeks. And HAC has good release characteristics as a drug delivery earricr.

The Behavior of New Hydrophilic Composite Bone Cements for Immediate Loading of Dental Implant

We introduced the hydrophilic groups to acrylic bone cement to improve compliance and achieve more interdigitation between the bone and the acrylic bone cement in order to create better substrates for immediate loading. FTIR-ATR, contact angle, and maximum breach torque were employed for measurement. The results reveal that the introduction of hydrophilic functional groups has increased PMMA＇s surface hydrophilicity after contact angle test. FTIR-ATR results suggest the hydrophilic groups participate in the polymerization reactions, and maximum breach torque of the hydrophilic acrylic bone cements is near 110 Ncm torque. Those effects make it possible for conventional acrylic bone cement application in immediate loading of dental implant.

Formation and Characterization of Bone-like Nanoscale Hydroxyapatite in Glass Bone Cement

Glass based bone cement (GBC) was synthesized by mixing CaO-SiO2-P2O5 based glass powder with ammonium phosphate liquid medium. Bone-like hydroxyapatite (HAP, Ca10(PO4)6(OH)2) was found to form after GBC was immersed in simulated body fluid (SBF). HAP crystal grew with an increasing time along c axle and reached about 200 nm in length after 30 days, however, the end plane granularity remained 30-50 nm. The chemical composition, crystal structure and morphology of HAP formed from GBC were proved to have great resemblance with living HAP. It is believed that GBC was a desirabie biomedicai material with high bioactivity. Furthermore, the high compressive strength guaranteed the possibility of GBC in clinical application.

Biological Evaluation of α-TCP/TTCP Composite Bone Cement

tricalcium phosphate(α TCP)/tetracalcium phosphate(TTCP) composite bone cement had good hydration characteristic.In our system,α TCP/TTCP powder mixture was mixed with water at a powder/liquid (P/L) ratio of 1.50g·mL -1 .The setting time could be adjusted,the maximum compressive strength was 45.36MPa,and the hydration product was hydroxyapatite (HAP).In vitro biological simulated experiments indicate that α TCP/TTCP bone cement has α certain dissolubility.The hardened product is mainly HAP after soaking in simulated body fluid (SBF) for 10 weeks.The results of in vitro test and animal experiments and SEM analyses show that no local or general toxicity response,no muscle stimulation,no haemolysis,no cruor,no inflammatory reaction and no exclusion response are caused by α TCP/TTCP cement, which can be contributed to bone tissue spreading and impinging.α TCP/TTCP cement hydrated and hardened continually in vivo.The materials fused with host bone together with implanting time prolonging.Therefore,it is believed that α TCP/TTCP composite bone cement has a high biocompatibility and bioactivity,a certain biodegradation and good osteogenesis as well.

Mechanical Behaviour of Composite Bioactive Bone Cements Consisting of Two Different Types of Surface Treated Hydroxyapatite as Filler

Bioactive bone cements based on a paste-paste system for orthopaedic applications were developed consisting of hydroxyapatite （ HA ） filler panicles in a methacrylate matrix comprising urethane dimethacrylate （ UDMA ） and triethylene glycol dimethacrylate （ TEGDMA ）. To improve the interface between inorganic filler and organic matrix the HA panicles were subjected to two different surface treatment methods, using polyacrylic acid （PAA） and γ-methacryloxy propyl trimethoxy silane （γMPS）. The aim of the present study was to determine the influence of surface treatment and the inclusion of multifunctional methacrylates on the mechanical properties, namely 3-point flexural strength （FS） and fracture toughness of the cements and the effect of ageing in simulated body fluid. Comparing the mechanical properties of the two cements, the γMPS- HA cement showed that the fracture toughness of the experimental bone cements were significantly greater （ p 〈 0.001） compared to that of the PMMA cement, whereas PAA-HA containing cement had strength vollues around 20% lower. Interestingly, PAA was found to be more effective in improving the interface as the PAA treated HA cement （ UTHAPPA ） maintained its strength on immersion in SBF, suggesting that PAA provided a coupling, which was less sensitive to moisture, a similar trend was also observed with the inclusion of the carboxyl containing multifunctional methacrylates.

Effect on Hydration and Hardening of Tricalcium Phosphate Bone Cement

The bioactive α-Ca3（ PO4 ）2 bone cement was studied by XRD , SEM and isothermal calorimetric measurements. The results showed that a mixed pattern of TCP and hydroxylapatite were obtained after hydration and hardening. The mechanism of hydration and hardening of the α-Ca3 （ PO4）2 was dissolution-precipitation, （ NH4 ） 112 PO4 was the best set accelerator to the α-Ca3 （ PO4）2 cement, and the HAP powers and the （ NH4）H2 PO4 concentration had a great effect on the hydration rate of a-Ca3（ PO4）2.

Preparation and Compressive Strength of Calcium Phosphate Bone Cement Containing N,O-carboxymethyl Chitosan

N, O-carboxymethyl chitosan （ CMCTS ）, a kind of biodegradable organic substance, was added to calcium phosphate bone cement （CPC） to prodnce a composite more similar in composition to human bone. The compressive strength of the new material was inereased by 10 times compared with conventional CPC.

Periprosthetic joint infections in femoral neck fracture patients treated with hemiarthroplasty–should we use antibiotic-loaded bone cement?

BACKGROUND Hemiarthroplasty is the most common treatment in elderly patients with displaced intra-capsular femoral neck fracture(FNF).Prosthetic joint infection(PJI)is one of the most feared and frequent complications post-surgery because of the frail health status of these patients and the need for fast track surgery.Therefore,priorities should lie in effective preventive strategies to mitigate this burden.AIM To determine how much the implementation of the routine use of antibioticloaded bone cement(ALBC)as a relatively easy-to-apply amendment to the surgical practice reduces the infection rate in our hemiarthroplasty cohort.METHODS We retrospectively assessed all demographic,health status and treatment-related data of our FNF patients undergoing cemented hemiarthroplasty in the period from 2011 to 2017;241 patients were further analyzed after exclusion of patients with cancer-related sequelae and those who died before the end of the 1-year observation period.The PJI rate as diagnosed on basis of the Musculoskeletal Infection Society(MSIS)criteria 2011 was determined for each included patient and compared in function of the bone cement used for hip stem fixation.Patients were split into a group receiving a plain bone cement in the period from January 2011 to June 2013(non-ALBC group)and into a group receiving an ALBC in the period July 2013 to December 2017(ALBC group).Data analysis was performed with statistical software.We further calculated the cost-efficacy of the implementation of routine use of ALBC in the second group balancing the inhospital infection related treatment costs with the extra costs of use of ALBC.RESULTS In total 241 FNF patients who received cemented hemiarthroplasty in the period from January 2011 to January 2017 were eligible for inclusion in this retrospective study.There were 8 PJI cases identified in the ALBC group among n=94 patients,whereas 28 PJI cases were observed in the non-ALBC group among n=147 patients.The statistical analysis showed an infection risk reduction of 55.3%(in particular due to the avoidance of chronic delayed infections)in the ALBC group(95%CI:6.2%-78.7%;P=0.0025).The cost-evaluation analysis demonstrated a considerable cost saving of 3.500€per patient,related to the implementation of routine use of ALBC in this group.CONCLUSION Use of ALBC is a potent infection preventive factor in FNF patients receiving cemented hemiarthroplasties.It was further found to be highly cost-effective.

Antibiotic Bone Cement and Ultraviolet Light Use in Total Knee Arthroplasty

Objective: The purpose of this study was to determine usefulness of antibiotic bone cement and UV light in primary Total Knee Arthroplasty (TKA). Patients and Methods: Between 1986 and 2008, 3105 TKAs were performed using 750 mg of cefuroxime per bag of cement (Group 1), 7537 using cefuroxime and UV light (Group 2), and 4573 using UV light and gentamicin premixed (Group 3). Results: The primary infection rate was 0.57% (87 acute postoperative infections). Of these, 27 (0.9%) were in Group 1, 44 (0.6%) were in Group 2, and 16 (0.35%) were in Group 3 (p = 0.0013). Kaplan-Meier survival in Groups 1 - 3 for reoperation for aseptic loosening of any component at 5 years was 0.9908, 0.9927, and 0.9959, respectively (p = 0.1315). Conclusion: Despite potential concerns mentioned in the literature, these results continue to support the use of antibiotic bone cement and UV lights during TKA.

Successful Resuscitation of Bone Cement Implantation Syndrome in a Patient with Pre-Existing Pulmonary Hypertension: A Case Report

Background: In patients with pre-existing pulmonary hypertension undergoing surgery, there is an inherent risk of decompensation and right ventricular failure. Cemented hemi-arthroplasty in patients with pre-existing pulmonary hypertension predisposes them even more to morbidity and mortality from bone cement implantation syndrome (BCIS) with worsening of pulmonary hypertension. This risk should be recognized and steps taken for increased awareness, risk counselling and minimization of adverse effects. Case: We report a case of successful resuscitation of a patient with pre-existing pulmonary hypertension who developed 2 episodes of cardiac arrests—Grade 3 BCIS, shortly after cement implantation. Learning Points: Patients with pre-existing pulmonary hypertension for cemented hemi-arthroplasty are at additional risks and should be identified. Adequate risk counselling needs to be undertaken prior to surgery. A multi-disciplinary team effort is required. Discussion should be undertaken with the orthopaedic surgeon about the risks and benefits of using cemented implants. The anaesthetist needs to be vigilant for signs of BCIS, especially at the time of cement implantation and institute immediate resuscitation. Supportive treatment is the mainstay of management.

Osteogenesis Capacity of a Novel BMP/α-TCP Bioactive Composite Bone Cement

To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration characteristic of bone cement was evaluated. Animal experiments including histological observation, radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,a-TCP bone cement and BMP/α-TCP composite bone cement. Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property. Comparison experiments show that BMP/ α-TCP composite bone cement has a stronger osteogenesis ability. The gross observation of the implant site does not exhibit any inflammation or necrosis. Histological analyses reveal that the material has good osteointegration with host bone, and new bone formation is detected within the materials, which are degrading. Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation. Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement. This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability. Key words α-tricalcium phosphate (α-TCP) - bone morphogenetic proteins (BMP) - bone cement - osteogenesis - osteoinductivity - bone tissue engineering Funded by 863 Hi-Tech Research and Development Program of China (2002AA326080) and the Fund for Outstanding Young Teacher of the Education Ministry of China(2002123)

Polymethylmethacrylate bone cements and additives: A review of the literature

Polymethylmethacrylate(PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950 s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index(< 15%) vitamin E and low index(< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan(15% w/w PMMA) and silver(1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties.