Antibiotic-eluting resorbable bone-void filler evaluated in a large animal infection prevention model.

Periprosthetic infection in total knee arthroplasty is a difficult-to-treat complication. Current implant revision procedures use non-degradable, antibiotic-loaded bone cement for local antimicrobial delivery. As a permanent foreign body, antibiotic-loaded bone cement is susceptible to bacterial colonisation after antibiotic release. In this first step, of a multi-study approach, an infection prevention model assessed a resorbable, antibiotic-eluting bone-void filler for preventing infection in a large animal model. Four groups of sheep were utilised to monitor antibiotic-eluting bone-void filler-induced osteoconductivity, infection prevention, and implant resorption. Explanted bone and surrounding tissues were evaluated using quantitative microbiology, backscattered electron microscopy, bone mineral apposition, and Sanderson's staining at the 12-week endpoint. Control groups received commercially available bone-void filler, implanted into a surgically created defect on the right medial femoral condyle. Experimental groups received six antibiotic-eluting bone-void filler devices placed into identically sized defects. One control and one experimental group tested osteoconductivity. An additional control and experimental group were each inoculated with 5 × 105 colony forming units/mL Staphylococcus aureus during implant placement for bactericidal effects. Osteoconductivity was confirmed for both antibiotic-eluting bone-void filler and commercially available bone-void filler. The experimental group inoculated with S. aureus showed no detectable bacteria at the study's 12-week endpoint, while infection controls required euthanasia 6-11 d post-inoculation due to infection. This large animal study validated this antibiotic-eluting bone-void filler as osteoconductive, in situ degradable, and bactericidal. All groups, except the infection control, exhibited bone formation comparable to commercial filler ProOsteon®500R.

Antibiotic elution and compressive strength of gentamicin/vancomycin loaded bone cements are considerably influenced by immersion fluid volume.

The effect of doubling the immersion fluid (eluate) volume on antibiotic concentrations and on mechanical stability from vancomycin and gentamicin loaded bone cements was investigated in vitro. Antibiotic loaded bone cements containing premixed 1.34% gentamicin antibiotic concentration in the cement powder (wt), premixed 1.19% gentamicin wt and 4.76% vancomycin wt and premixed 1.17% wt gentamicin additionally manually blended with 4.68% wt vancomycin were tested. Six specimens per group were immersed in 4 ml and 8 ml for 6 weeks while the eluate was exchanged every 24 h. The antibiotic concentrations were repeatedly measured. Then the specimens were tested for compressive strength. Doubling the eluate volume significantly decreased gentamicin and vancomycin concentrations from 6 h and 24 h on, except for the gentamicin concentration of the additionally manually blended formulation after 3 weeks. The additionally manually blended vancomycin formulation produced significantly higher gentamicin concentrations in 8 ml compared to the other formulations. The reduction ratios of the vancomycin concentrations were significantly smaller than the reduction ratios of the gentamicin concentrations for the manually blended vancomycin formulation. Vancomycin containing formulations showed significantly lower compressive strengths than the vancomycin free formulation after immersion. Doubling the eluate volume lead to significant compressive strength reduction of the vancomycin containing formulations. Eluate volume change influences antibiotic elution dependent on the antibiotic combination and loading technique. The reducing effect is higher on vancomycin than on gentamicin elution. Compressive strength of gentamicin/vancomycin loaded bone cements after immersion is eluate volume dependent.

Local and systemic diffusion of antineoplastic drugs following vertebroplasty using acrylic cement mixed with cisplatin or methotrexate: experimental study in pigs.

PURPOSE: To determine the efficacy of cisplatin- or methotrexate-containing acrylic cement for local and systemic antineoplastic drug diffusion. Among the uses of acrylic cement or Polymethylmethacrylate (PMMA), there is the possibility to employ it as vehicle for drug diffusion. This capability is of interest in the treatment of pathological fractures: The curative effects of the cement (cytotoxicity of the monomer and increased temperature) are added to the antineoplastic effect of the drugs. METHODS: In the experimental study, two groups of ten pigs underwent vertebroplasty using cement mixed with 500 mg of powder cisplatin or 1000 mg of powder methotrexate. Vertebroplasty was performed in two non-consecutive lumbar vertebrae with bipedicular cement injection. Transpedicular bone biopsy was performed weekly to measure levels of antineoplastic agent in bone tissue and blood plasma. Cisplatin was studied by atomic absorption spectrometry and methotrexate by fluorescence polarization immunoassay. Renal and hepatic function and blood analysis were performed weekly. RESULTS: Cisplatin and methotrexate levels were found in bone tissue at more than 5 weeks following surgery. The cisplatin peak occurred at week 3 (mean 1269 µg/g bone) and the methotrexate peak at week 1 (mean 862.76 µg/g bone). Plasma drug levels were found 72 h after surgery, with a peak at 24 h for cisplatin (mean 0.23 µmol/L) and at 30 min for methotrexate (mean 0.92 µmol/L). None of the animals died during the study. Animals with intracanal cement leaks showed no neurological involvement. Renal, hepatic and hemogram studies remained within normal limits. CONCLUSIONS: There is local diffusion of antineoplastic agents from the cement to bone and plasma. We found methotrexate and cisplatin levels in bone at up to 5 weeks, comparable to previous in vitro reports. At the doses administered, there were no cases of myelosuppression, hepatotoxicity, or nephrotoxicity.

Elution kinetics of vancomycin and gentamicin from carriers and their effects on mesenchymal stem cell proliferation: an in vitro study.

BACKGROUND: Musculoskeletal infections remain a major complication in orthopedic surgery. The local delivery of antibiotics provides the high levels required to treat an infection without systemic toxicity. However, the local toxicity of antibiotic carriers to the mesenchymal stem cells, as a result of both the peak concentrations and the type of carrier, may be significant. METHODS: To address this concern, the elution kinetics of vancomycin and gentamicin from several commercially available antibiotic carriers and several carriers impregnated by a surgeon (10 ml of each sterile carrier were manually mixed with a 500 mg vancomycin and an 80 mg gentamicin solution, and the duration of impregnation was 30 min) were assessed. Moreover, the effects of these antibiotic carriers on stem cell proliferation were investigated. The following two types of stem cells were used: bone marrow and dental pulp stem cells. RESULTS: The high eluted initial concentrations from antibiotic impregnated cancellous allogeneic bone grafts (which may be increased with the addition of fibrin glue) did not adversely affect stem cell proliferation. Moreover, an increased dental pulp stem cell proliferation rate in the presence of antibiotics was identified. In contrast to allogeneic bone grafts, a significant amount of antibiotics remained in the cement. Despite the favorable elution kinetics, the calcium carriers, bovine collagen carrier and freeze-dried bone exhibited decreased stem cell proliferation activity even in lower antibiotic concentrations compared with an allogeneic graft. CONCLUSIONS: This study demonstrated the benefits of antibiotic impregnated cancellous allogeneic bone grafts versus other carriers.

[An experimental study on a slow-release complex with rifampicin-polylactic-co-glycolic acid-calcium phosphate cement].

OBJECTIVE: To prepare the slow-release complex with rifampicin (RFP)-polylactic-co-glycolic acid (PLGA)-calcium phosphate cement (CPC) (RFP-PLGA-CPC complex), and to study its physical and chemical properties and drug release properties in vitro.
 METHODS: The emulsification-solvent evaporation method was adopted to prepare rifampicin polylactic acid-glycolic acid (RFP-PLGA) slow-release microspheres, which were divided into 3 groups: a calcium phosphate bone cement group (CPC group), a CPC embedded with RFP group (RFP-CPC group), and a PLGA slow-release microspheres carrying RFP and the self-curing CPC group (RFP- PLGA-CPC complex group). The solidification time and porosity of materials were determined. The drug release experiments in vitro were carried out to observe the compressive strength, the change of section morphology before and after drug release. 
 RESULTS: The CPC group showed the shortest solidification time, while the RFP-PLGA-CPC complex group had the longest one. There was statistical difference in the porosity between the CPC group and the RFP-CPC group (P<0.05); Compared to the RFP-PLGA-CPC complex group, the porosity in the CPC group and the RFP-CPC group were significantly changed (both P<0.01). There was significant difference in the compressive strength between the RFP- PLGA-CPC complex group and the CPC group (P<0.01), while there was significant difference in the compressive strength between the RFP-CPC group and the CPC group (3 days: P<0.05; 30 and 60 days: P<0.01). The change of the compressive strength in the CPC was not significant in the whole process of degradation. The sizes of PLGA microspheres were uniform, with the particle size between 100-150 µm. The microspheres were spheres or spheroids, and their surface was smooth without the attached impurities. There was no significant change in the section gap in the CPC group after soaking for 3 to 60 days. The microstructure change in the RFP-CPC group was small, and the cross section was formed by small particles. The pores of section in the RFP-PLGA-CPC complex group increased obviously, and PLGA microspheres gradually disappeared until the 60th day when there were only empty cavities left. The RFP-PLGA-CPC complex group had no obvious drugs sudden release, and the cumulative drug release rate was nearly 95% in the 60 days. The linear fitting was conducted for the drug release behavior of the complex, which was in accordance with zero order kinetics equation F=0.168×t.
 CONCLUSION: The porosity of RFP-PLGA-CPC complex is significantly higher than that of CPC, and it can keep slow release of the effective anti-tuberculosis drugs and maintain a certain mechanical strength for a long time.

Evaluation of Elution and Mechanical Properties of High-Dose Antibiotic-Loaded Bone Cement: Comparative "In Vitro" Study of the Influence of Vancomycin and Cefazolin.

Use of antibiotic-loaded bone cements is one of the most effective methods for the prevention and treatment of prosthetic joint infection. However, there is still controversy about the optimal combination and doses of antibiotics that provide the maximum antimicrobial effect without compromising cement properties. In this study, vancomycin and cefazolin were added to a bone cement (Palacos R+G). Antibiotic release, fluid absorption, and mechanical properties were evaluated under physiological conditions. The results show that the type of antibiotic selected has an important impact on cement properties. In this study, groups with cefazolin showed much higher elution than those containing the same concentration of vancomycin. In contrast, groups with cefazolin showed a lower strength than vancomycin groups.

Elution of High Dose Amphotericin B Deoxycholate From Polymethylmethacrylate.

Fungal periprosthetic joint infections are rare, devastating complications of arthroplasty. There is conflicting evidence as to the efficacy of amphotericin B elution from cement spacers. The purpose of this study was to determine whether concentrations of amphotericin B released from bone cement over time would be efficacious in treating a periprosthetic infection. A continuous flow chamber was used to evaluate the in vitro release of amphotericin from cement beads containing 7.5% amphotericin. Following polymerization, 3.3% of the initially loaded amphotericin B was detected. The peak mean concentration eluted from the bone cement was 0.33 µg/mL at 8 hours. The AUC0-24 was 2.79 µg/mL/h; 0.20% of the amphotericin B was released. In conclusion, amphotericin B is released from bone cement at a clinically useful concentration.

Liquid dextran does not increase the elution rate of different antibiotics from bone cement.

PURPOSE: To investigate the possibility of increasing elution of fosfomycin, gentamicin, clindamycin, and vancomycin by the addition of dextran fluid during the cement-mixing phase. METHODS: In 12 test series, we produced standardized, antibiotic-loaded test specimens of cement, with and without addition of dextran, and determined their effectiveness against three reference pathogens in agar diffusion and elution tests. RESULTS: In the test series using combined agents, Refobacin(®)-Palacos(®)R plus fosfomycin continuously produced the largest zone of inhibition, both against methicillin-sensitive Staphylococcus aureus (p = 0.009) and against methicillin-resistant Staphylococcus aureus (p = 0.009). The addition of dextran to the various test series had no useful effect on the size of the zone of inhibition for any of the antibiotics tested. CONCLUSIONS: Dextran supplementation in Refobacin(®)-Palacos(®)R bone cement did not have the hope for positive effect on the elution rate of bound antibiotics.

Biomechanical characteristics of cement/gelatin mixture for prevention of cement leakage in vertebral augmentation.

PURPOSE: This study evaluated whether or not the addition of gelatin micro-particles into the polymethyl methacrylate (PMMA) could reduce cement infiltration in cancellous bone of vertebra. METHODS: Gelatin micro-particles were prepared in various sizes and mixed with PMMA in different densities. Dynamic viscosity of the mixture was measured by a rotational rheometer. Fresh bovine vertebral bodies were sectioned into cylindrical samples. Permeability of the mixture through the samples was tested on a mechanical test machine, and calculated using Darcy's law. The PMMA/gelatin mixture also underwent compressive and bending tests, and their structures were examined by scanning electron microscopy. RESULTS: The cement/gelatin mixture increased the viscosity. Significant reduction of cement permeability in cancellous bone was determined after the addition of the micro-particles. Micro-particles of 2 % in density and 125-250 µm in size decreased the permeability by 1/3 without any significant change of the cement viscosity. The biomechanical strength was unchanged in compression but decreased by up to 20 % in bending. CONCLUSIONS: Gelatin micro-particles significantly increased the cement viscosity, reduced the permeability in cancellous bone of vertebra, decreased the flexural strength, but did not affect the compressive strength. Although it suggested a manageable approach in vertebral augmentation, the outcome should be further verified on a cadaveric model or an animal model before the mixture could be used safely and effectively in the clinical treatment.

Premixed injectable calcium phosphate cement with excellent suspension stability.

Premixed injectable calcium phosphate cement (p-ICPC) pastes have advantages over aqueous injectable calcium phosphate cement (a-ICPC) because p-ICPC remain stable during storage and harden only after placement into the defect. This paper focused on the suspension stability of p-ICPC paste by using fumed silica as a stabilizing agent and propylene glycol (PEG) as a continuous phase. Multiple light scanning techniques were first applied to evaluate the suspension stability. The results indicated that fumed silica effectively enhanced the suspension stability of p-ICPC pastes. The stabilizing effect of fumed silica results from the network structure formed in PEG because of its thixotropy. The p-ICPC could be eventually hydrated to form hydroxyapatite under aqueous circumstances by the unique replacement between water and PEG. p-ICPC (1) not only possesses proper thixotropy and compressive strength but has good injectability as well. p-ICPC (1) was cytocompatible and had no adverse effect on the attachment and proliferation of MG-63 cells in vitro. These observations may have applicability to the development of other nonaqueous injectable biomaterials for non-immediate filling and long-term storage.

Development and bioactivity evaluation of bioglasses with low Na2O content based on the system Na 2O-CaO-MgO-P 2O 5-SiO 2.

Osteoconductive bioglasses, free of K(2)O and Al(2)O(3) and with content of Na(2)O lower than 10 mol%, were designed based on the ratio (SiO(2) + MgO)/(P(2)O(5) + CaO + Na(2)O) in the system Na(2)O-CaO-MgO-P(2)O(5)-SiO(2). The developed glasses have shown a strong potential for the formation of hydroxycarbonated apatite (HCA) in vitro. The particles of HCA aggregates tend to be of finer size with increasing the ratio of (SiO(2) + MgO)/(CaO + P(2)O(5) + Na(2)O) in the glass chemical composition indicating significant bioactivity. Critical size bone defects created in the femurs of albino adult female rats, and grafted with the glass particles for 12 weeks post implantation, were completely healed by filling with mineralized bone matrix without infection showing a strong potential for new bone formation in vivo. Osteoblasts and osteocytes were observed close to the surface of the granular implants with active areas of bone deposition, resorption and remodelling. The bioglass with lowest (SiO(2) + MgO)/(CaO + P(2)O(5) + Na(2)O) ratio has shown the highest bioactivity while the bioglass with the highest (SiO(2) + MgO)/(CaO + P(2)O(5) + Na(2)O) has shown the lowest bioactivity. The newly formed bone in vivo has shown a similar structure to that of the original bone as indicated by the histology and microstructural results. In addition, Ca/P molar ratio of the newly formed bone was found to be (~1.67), which is similar to that of the original bone.

Bonding ability evaluation of bone cement on the cortical surface of rabbit's tibia.

A composite bone cement designated G2B1 that contains beta tricalcium phosphate particles was developed as a bone substitute for percutaneous transpedicular vertebroplasty. In this study, both G2B1 and commercial PMMA bone cement (CMW1) were implanted into proximal tibiae of rabbits, and their bone-bonding strengths were evaluated at 4, 8, 12 and 16 weeks after implantation. Some of the specimens were evaluated histologically using Giemsa surface staining, contact microradiography (CMR) and scanning electron microscopy (SEM). Histological findings showed that G2B1 contacted bone directly without intervening soft tissue in the specimens at each time point, while there was always a soft tissue layer between CMW1 and bone. The bone-bonding strength of G2B1 was significantly higher than that of CMW1 at each time point, and significantly increased from 4 weeks to 8 and 12 weeks, while it decreased significantly from 12 weeks to 16 weeks. Bone remodeling of the cortex under the cement was observed especially for G2B1 and presumably influenced the bone bonding strength of the cement. The results indicate that G2B1 has bioactivity, and bone bonding strength of bioactive bone cements can be estimated fairly with this experimental model in the short term.

Morphological changes of injected calcium phosphate cement in osteoporotic compressed vertebral bodies.

SUMMARY: This study was undertaken to investigate the radiologic and clinical outcomes of vertebroplasty with calcium phosphate (CaP) cement in patients with osteoporotic vertebral compression fractures. The morphological changes of injected CaP cement in osteoporotic compressed vertebral bodies were variable and unpredictable. We suggest that the practice of vertebroplasty using CaP should be reconsidered. INTRODUCTION: Recently, CaP, an osteoconductive filler material, has been used in the treatment of osteoporotic compression fractures. However, the clinical results of CaP-cement-augmented vertebrae are still not well established. The purpose of this study is to assess the clinical results of vertebroplasty with CaP by evaluating the morphological changes of CaP cement in compressed vertebral bodies. METHODS: Fourteen patients have been followed for more than 2 years after vertebroplasty. The following parameters were reviewed: age, sex, T score, compliance with osteoporosis medications, visual analog scale score, compression ratio, subsequent compression fractures, and any morphological changes in the filler material. RESULTS: The morphological changes of injected CaP included reabsorption, condensation, bone formation (osteogenesis), fracture of the CaP solid hump, and heterotopic ossification. Out of 14 patients, 11 (78.6%) developed progression of the compression of the CaP-augmented vertebral bodies after vertebroplasty. CONCLUSIONS: The morphological changes of the injected CaP cement in the vertebral bodies were variable and unpredictable. The compression of the CaP-augmented vertebrae progressed continuously for 2 years or more. The findings of this study suggest that vertebroplasty using CaP cement should be reconsidered.

2008 Otto Aufranc Award: component design and technique affect cement penetration in hip resurfacing.

Either excessive or insufficient cement penetration within the femoral head after hip resurfacing influences the risk of femoral failures. However, the factors controlling cement penetration are not yet fully understood. We determined the effect of femoral component design and cementation technique on cement penetration. Six retrieved femoral heads were resurfaced for each implant (BHR, ASR, Conserve Plus, DuROM, ReCAP) using the manufacturers' recommendations for implantation. In addition, the BHR was implanted using the Conserve Plus high-viscosity cementation technique, "BHR/hvt," and vice versa for the Conserve, "Conserve/lvt." The average cement penetration was highest with BHR (65.62% +/- 15.16%) compared with ASR (12.25% +/- 5.12%), Conserve Plus(R) (19.43% +/- 5.28%), DuROM (17.73% +/- 3.96%), and ReCAP (26.09% +/- 5.20%). Cement penetration in BHR/hvt remained higher than all other implants equaling 36.7% +/- 6.6%. Greater femoral component design clearance correlated with cement mantle thickness. Femoral component design in hip resurfacing plays a major role in cement penetration.

Elution of ciprofloxacin from acrylic bone cement and fibrin clot: an in vitro study.

The purpose of this study was to investigate the release of ciprofloxacin from acrylic bone cement and fibrin clot. Under sterile conditions, bone cement and fibrin clot were individually mixed with ciprofloxacin. Ten specimens of each complex were placed in 1 ml of nutrient broth and incubated at 37 degrees C. The nutrient broth was changed daily, and the removed samples were stored at -70 degrees C until the antibiotic concentration in each sample was determined by a microbiological method. The maximum level in bone cement specimens was obtained at the second day (80.80 microg/ml) and its diffusion was rapid at first, decreasing gradually over a period of 365 days. Fibrin clot biodegradable specimens released high concentrations of ciprofloxacin (1.52-49.91 microg/ml) in vitro for the period of time needed to treat bone infections (i.e. 65 days). We conclude that the high release of ciprofloxacin in vitro from acrylic bone cement and fibrin clot is very promising since the obtained levels are much higher than the required minimal inhibitory concentration (MIC) against the implicated pathogens in soft tissue and bone infections. The in vivo relevance of the obtained results requires carefully performed studies in animal models.

Cement Distribution Patterns in Osteoporotic Vertebral Compression Fractures with Intravertebral Cleft: Effect on Therapeutic Efficacy.

OBJECTIVE: To determine cement distribution patterns on therapeutic efficacy after percutaneous vertebroplasty treatment of osteoporotic vertebral compression fractures (OVCFs) with intravertebral cleft (IVC). METHODS: Patients who were treated with percutaneous vertebroplasty for single OVCFs with IVC and met this study's inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Distribution patterns of cement in the IVC area were respectively specified into 2 groups: group 1: solid lump distribution pattern (n = 22); group 2: the comparatively diffused pattern (n = 90). Radiologic and clinical parameters were analyzed and compared. Then, associations of recollapse with covariates and a risk score were further analyzed and developed to predict recollapse of the augmented vertebrae. RESULTS: At the immediate postoperative period, all patients benefited from significant improvement in vertebrae height and kyphotic angle correction. However, significant recollapse was observed at the 2 years postoperative follow-up for the patients in group 1. Furthermore, we found that preoperative severe kyphotic deformity (a cutoff value of 12.5°), solid lump cement distribution pattern, and larger reduction angle (a cutoff value of 8.3°) was significantly associated with increased risk for recollapse. A risk score was developed based on the number of risk factors present in each patient and the receiver operating characteristic curve of the risk score generated an area under the curve of 0.788 (95% confidence interval 0.702-0.873, P = 0.000). CONCLUSIONS: The comparatively diffused pattern shows better long-term radiologic and clinical outcomes for the treatment for OVCFs with IVC. A risk score can be used to predict the incidence of recollapse.

Copal bone cement is more effective in preventing biofilm formation than Palacos R-G.

Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G.

Comparison of CT characteristics of extravertebral cement leakages after vertebroplasty performed by different navigation and injection techniques.

OBJECTIVE: This study was intended to assess the results of post-operative CT scans in three groups of patients following percutaneous vertebroplasty (VP) using different navigation and injection methods, in an attempt to explain the radiological characteristics of extravertebral cement leakage with relation to needle placement and focused on the ventral epidural accumulation of bone cement. Furthermore, we have suggested a morphological (and functional) classification of the types of cement leakage. METHODS: Between July 2001 and February 2005, 123 percutaneous VP procedures were performed during 75 sessions in 65 patients for treatment of painful osteoporotic vertebral body compression fractures. These included:- Group I: 28 patients, 33 sessions; 50 right sided unilateral VP under fluoroscopic control with central position of the tip of the needle within the bone marrow. Group II: 27 patients, 28 sessions; 50 bilateral VP under fluoroscopic control with separate cement injections into both "hemivertebrae". Group III: 14 patients, 14 sessions; 23 bilateral VP navigated by frameless stereotaxy (neuronavigation). Needles were positioned strictly into the lateral thirds of the vertebral bodies. Leakages were classified as epidural, foraminal, intradiscal, venous paravertebral, compact extravertebral on the post-operative CT scans, and their frequency was compared in relation to the navigation method and the position of the tip of the needle. RESULTS: Group I: extravertebral cement was detected in 23 patients (82%), and in 35 (70%) of the 50 vertebrae treated (ventral epidural: 23 vertebrae = 46%; intradiscal: 12 vertebrae = 24%; venous paravertebral: 8 vertebrae = 16%; intraforaminal: 7 vertebrae = 14%; and compact extravertebral: 3 vertebrae = 6%). Group II: extravertebral cement was detected in 20 patients (74%), and in 38 (76%) of the 50 vertebrae treated (ventral epidural: 12 vertebrae = 24%; intradiscal: 12 vertebrae = 24%; venous paravertebral: 9 vertebrae = 18%; and foraminal: 1 vertebra = 2%). Group III: extravertebral cement could be detected in 10 patients (71%), and in 10 (43%) of the 23 vertebrae treated (ventral epidural: 3 vertebrae = 13%; intradiscal: 8 vertebrae = 34%; venous paravertebral: 4 vertebrae = 17%). CONCLUSION: The incidence of epidural accumulation of bone cement may be concluded to be closely correlated with the position of the tip of the needle. Centrally injected bone cement may easily invade into the basivertebral system, and the material can then be transferred via these veins toward the ventral epidural space, and result in canal compromise and/or compression of the neural elements. The results of statistical analysis (Chi-square test) revealed that injection of bone cement into the lateral third of the vertebral body significantly decreases the extent of ventral epidural leakage. Therefore, a strictly lateral injection is advised, when the tip of the needle is placed into the lateral third of the vertebral body. Frameless stereotaxy navigation improves achievement of accurate needle placement and decreases the frequency of ventral epidural leakage. It is a safe and very accurate method for positioning of the injecting needles.

The effects of methyl methacrylate monomer on testosterone level in male rats. An experimental study.

INTRODUCTION: Methyl methacrylate (MMA) is commonly used in medicine and dentistry. The adverse effects of MMA are well described in the literature. Animal studies have largely confirmed the risks reported in clinical observations. There is no study indicating direct implication of MMA on male fertility mechanism. OBJECTIVES: The purpose of this study was to determine whether MMA is able to modify the testosterone level. METHODS: The target population consisted of 60 male Sprague-Dawley rats. They were closed in colony cages and divided into five groups: The first group (n=15) designated as the control group and four experimental groups (n=45). Experiments were conducted by exposing the four experimental groups to MMA with water at different concentrations (4% per hundred, 8% per hundred, 16% per hundred and 32% per hundred) administered per os. The exposure duration was eight months. Blood was obtained before and at the end of the exposure and the measurement of the testosterone level was made by EIA test. RESULTS: The exposure of rats at a moderate concentration of MMA (16% per hundred) showed an increase in testosterone level of 60% (p = 0.003) while the other groups showed a decrease of testosterone level. The control group showed a decrease of 44.8% (p = 0.001), the rats exposed at 4% per hundred showed a decrease of 67.7% (p = 0.000), those exposed at 8% per hundred showed a decrease of 432% (p = 0.35), the rats exposed at 32% per hundred showed a decrease of 71.7% (p = 0.002). CONCLUSION: Despite the fact that MMA at low concentration was rapidly hydrolyzed in blood due to the nonspecific carboxylesterase and metabolized at high concentration by the liver, its effects on testosterone level were significant. These preliminary results showed an interference of the MMA with the testosterone hormonal equilibrium that could be an interesting target for further investigations.

Antibiotic-loaded cement spacers - lessons learned from the past 20 years.

INTRODUCTION: The use of antibiotic-impregnated cement spacers is an established method in the treatment of periprosthetic hip and knee joint infections. Over the past 20 years, the indications for spacer implantation have expanded, and various modified surgical techniques have been proposed to manage difficult anatomical situations. To ensure clinical success, knowledge about the cement impregnation and the pharmacokinetic properties of antibiotic-loaded bone cement is an indispensable premise. AREAS COVERED: In this review, techniques for the fabrication of cement spacers, the incorporation of antibiotics into bone cement, elution kinetics, the clinical performance of spacers, individualized surgical techniques as well as possible postoperative complications are presented. Moreover, the possibility of bacterial colonization of cement spacers during the interim phase which might lead to persistence of infection is also discussed. EXPERT COMMENTARY: The use of articulating spacers is established in hip surgery. However, in knee surgery it is still debated whether articulating or static spacers provide more advantages. The concern about the possible colonization of antibiotic-loaded spacers during the interim phase does not seem to be actually substantiated by hard scientific data due to the lack of important information in the published studies.