Elevated blood metal ion levels in patients undergoing instrumented spinal surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Elevated blood metal levels have been reported in patients after spinal surgery using metallic implants. Although some studies have suggested an association between heightened blood metal concentrations and potential adverse effects, estimates of the incidence of abnormal metal levels after spinal surgery have been inconsistent. PURPOSE: The aims of this systematic review and meta-analysis were to assess: (1) mean differences in blood metal ion levels between patients undergoing spinal fusion surgery and healthy controls, (2) odds of elevated blood metal ion levels after surgery compared to presurgery levels, and (3) pooled incidence of elevated blood metal ions overall and by metal type. STUDY DESIGN: Systematic review and meta-analysis. PATIENTS SAMPLE: The patient sample included 613 patients from 11 studies who underwent spinal surgery instrumentation. OUTCOME MEASURES: Blood metal ion concentrations and the incidence of patients with elevated metal levels compared with in those the control group. METHODS: A comprehensive search was conducted in PubMed, EMBASE, Scopus, and Cochrane Library to identify studies reporting blood metal ion levels after spinal fusion surgery. Mean differences (MD), odds ratios (OR), and incidence rates were pooled using random effects models. Heterogeneity was assessed using I2 statistics, and fixed-effects models were used if no heterogeneity was detected. Detailed statistical analysis was performed using the Review Manager version 5.4 software. RESULTS: The analysis included 11 studies, with a total of 613 patients. Mean blood metal ion levels were significantly higher after spinal fusion surgery (MD 0.56, 95% CI 0.17-0.96; I2=86%). Specifically, titanium levels were significantly elevated (MD 0.81, 95% CI 0.32-1.30; I2=47%). The odds of elevated blood metal ions were higher after surgery (OR 8.17, 95% CI 3.38-19.72; I2=41%), primarily driven by chromium (OR 23.50, 95% CI 5.56-99.31; I2=30%). The incidence of elevated chromium levels was found to be 66.98% (95% CI 42.31-91.65). CONCLUSION: In conclusion, blood metal ion levels, particularly titanium and chromium, were significantly increased after spinal fusion surgery compared to presurgery levels and healthy controls. Approximately 70% of the patients exhibited elevated blood levels of chromium and titanium.

Benefits and Biosafety of Use of 3D-Printing Technology for Titanium Biomedical Implants: A Pilot Study in the Rabbit Model.

BACKGROUND: Titanium has been used in osteosynthesis for decades and its compatibility and safety is unquestioned. Studies have shown that there is release and collection of titanium in the organ systems with little note of toxicity. The gold standard is considered to be titanium osteosynthesis plate produced by milling methods. The use of customized titanium plates produced with 3D printing, specifically direct metal laser sintering, have found increasing use in recent years. It is unknown how much titanium is released in these printed titanium implants, which is known to be potentially porous, depending on the heat settings of the printer. We hypothesize that the amount of titanium released in printed titanium implants may be potentially more or equal compared to the gold standard, which is the implant produced by milling. METHODS: We studied the biosafety of this technology and its products by measuring serum and organ titanium levels after implantation of 3D-printed versus traditionally fabrication titanium plates and screws in a pilot study using the rabbit model. A total of nine rabbits were used, with three each in the control, milled and printed titanium group. The animals were euthanized after six months. Serum and organs of the reticuloendothelial system were harvested, digested and assayed for titanium levels. RESULTS: Organ and serum titanium levels were significantly higher in rabbit subjects implanted with titanium implants (milled and printed) compared to the control group. However, there was no significant difference in organ and serum titanium levels of subjects implanted with milled and traditionally fabricated titanium implants. CONCLUSIONS: The biosafety of use of 3D-printed titanium implants and traditionally fabricated titanium implants are comparable. With this in mind, 3D-printed custom implants can not only replace, but will very possibly surpass traditionally fabricated titanium implants in the mode and extent of use.

The unfavorable role of titanium particles released from dental implants.

Titanium is considered to be a metal material with the best biological safety. Studies have proved that the titanium implanted in the bone continuously releases titanium particles (Ti particles), significantly increasing the total titanium content in human body. Generally, Ti particles are released slowly without causing a systemic immune response. However, the continuous increased local concentration may result in damage to the intraepithelial homeostasis, aggravation of inflammatory reaction in the surrounding tissues, bone resorption and implant detachment. They also migrate with blood flow and aggregate in the distal organ. The release of Ti particles is affected by the score of the implant surface structure, microenvironment wear and corrosion, medical operation wear, and so on, but the specific mechanism is not clear. Thus, it difficult to prevent the release completely. This paper reviews the causes of the Ti particles formation, the damage to the surrounding tissue, and its mechanism, in particular, methods for reducing the release and toxicity of the Ti particles.

Environmental titanium exposure and reproductive health: Risk of low birth weight associated with maternal titanium exposure from a nested case-control study in northern China.

Titanium (Ti) is commonly used in additives in the form of titanium dioxide (TiO2). However, our understanding of the effect of Ti on reproductive health remains limited. This nested case-control study, performed in a Ti mining exposure field, investigated the association between maternal blood Ti concentration and the risk of low birth weight (LBW), as well as the potential biological mechanism. A total of 45 women who delivered LBW infants (cases) and 352 women with normal birth weight infants (controls) were included. We collected maternal peripheral blood samples in the first or early second trimester to measure Ti concentration in serum (Tisr) and blood cells (Tibc), as well as inflammatory, lipid, and oxidative stress biomarkers thereof. The demographic characteristics of the women included in the study were also obtained. The results showed that the median total blood Ti concentration (Titb) in the case group was significantly higher than that in the control group (134 vs. 129 ng/mL, P = 0.039). A higher Titb level was associated with a greater risk of LBW [odds ratio = 2.62; 95% confidence interval (CI): 1.16-5.90], but no such association was observed for Tisr or Tibc after adjusting for potential confounders. The serum lipid biomarkers TC, TG, and total lipids (TL) were all negatively associated with Tisr and Titb. Serum 8-OHdG was positively associated with Tibc. We concluded that a high Titb during early pregnancy may increase the risk of LBW. Lipid metabolism and oxidative stress may play an important role in the adverse health effects associated with Ti exposure. Thus, our results merit more attention to the probable adverse effects of titanium exposure during pregnancy.

Plasma titanium level is positively associated with metabolic syndrome: A survey in China's heavy metal polluted regions.

OBJECTIVE: Several heavy metals have been reported to be associated with metabolic syndrome(MetS) in general population, while effects of multiple metals exposure on MetS in residents living in heavy metal polluted regions have not been investigated. We aimed to assess the association of 23 metal levels and MetS among population living in China's heavy metal polluted regions. METHODS: From August 2016 to July 2017, a total of 2109 eligible participants were consecutively enrolled in our study in Hunan province, China. The levels of plasma and urine metals were measured by inductively coupled plasma mass spectrometer (ICP-MS). MetS was defined by the criteria of the International Diabetes Federation. Multivariable regression models were applied to analysis the potential relationship. RESULTS: In the overall population, crude model showed positive relationship of plasma titanium (Ti) with MetS and negative association of urine vanadium, iron, and selenium with MetS. After adjusted for potential confounders, only plasma Ti was positive associated with MetS (adjusted OR for Q4 versus Q1: 1.46; 95% CI: 1.06-1.99), and this positive correlation was explained by abdominal obesity (OR = 1.84, 95% CI: 1.41-2.39) and high triglycerides (OR = 2.23, 95% CI: 1.68-2.96). Further linear regression analysis revealed significant association of plasma Ti levels with waist circumference (ß = 0.0056, 95% CI: 0.0004-0.0109, P = 0.036) and triglycerides (ß = 0.0012, 95% CI: 0.0006-0.0019, P < 0.001), respectively. CONCLUSION: High plasma Ti level was associated with increased risk of MetS via increasing waist circumference and triglycerides in people under high metal exposure.

Unexpected varus deformity and concomitant metal ion release and MRI findings of modular-neck hip stems: descriptive RSA study in 75 hips with 8 years' follow-up.

Background and purpose - Modular-neck hip stems have been identified with corrosion-related problems from the neck-stem junction. We report an ongoing varus deformity of modular-neck hip stems with simultaneous metal ion release observed during a study comparing the migration of modular vs. standard hip stems.Patients and methods - We followed 50 patients with modular and 25 with standard neck stems using radiostereometry (RSA). At 5-year follow-up, we noted a compromised integrity of the modular stem with varus deformity in the neck-stem interface. Changes in head-tip distance as well as whole-blood ion concentration and MRI findings were analyzed. The modular stems were followed further up to 8 years.Results - The head-tip distance decreased continuously by 0.15 mm per year resulting in 1.2 (95% CI 1.0-1.4) mm at 8 years for modular stems, while for the standard stems at 5 years, the decrease was 0.09 (CI 0.0-0.2) mm or 0.02 mm/year. For the modular stems, the reduction in head-tip distance correlated to the increase in whole-blood cobalt concentration at 8 years but not to the MRI grading of tissue reactions. At 5 years, cobalt levels were 4.9 µg/L for modular stems and at 8 years 4.8 µg/L, whereas for standard stems this was 1.0 µg/L. After 8 years, 9 of 72 stems had been revised for different reasons, but only 1 with obvious adverse local tissue reaction (ALTR).Interpretation - We present a surprisingly large progressive deformation at the modular neck-stem junction, but so far without a definite clinical problem. Even the femoral head seems to show slight compression onto the taper over time. A high rate of revisions for the modular type of this stem has raised general concerns, and it has been recalled from the market.

The effect of work environment on the biochemical profile of workers operating at the Ust-Kamenogorsk Titanium and Magnesium Plant.

This study explored biochemical parameters of blood in workers operating in the main workshops at the Ust-Kamenogorsk Titanium and Magnesium Plant: magnesium (Mg) workshop (furnace operator, chlorinator operator, and electrolyzer operator), titanium tetrachloride workshop (mill operator and titanium (Ti) production operator), and Ti sponge workshop (reduction furnace operator, knockout operator, and crushing machine operator). The control group consisted of 112 male workers, whose duties were not related to similar occupational hazards (plumbers, electricians, janitors cleaning the administrative building, security guards, and carpenters). The activity of gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, lactate dehydrogenase, cholinesterase, alkaline phosphate, and α-amylase and the concentration of serum calcium, Mg, phosphorus, and chloride ion were measured. To clarify the nature of pathological changes that occur in the body of mammals under the influence of toxic gases and dust, this study also included 130 sexually mature, white female rats. Animals and workers were exposed to examination of the same indicators. Changes in test results of enzymes and minerals indicated a negative impact that harmful production factors may have had on the bodies of workers. Findings showed significant fluctuations in enzyme and mineral blood profiles of workers as compared to controls. In the test animals, changes in the enzyme activity and mineral blood composition were as diverse as in the workers. These findings will be useful when identifying markers of a negative impact of harmful substances in an industrial workplace and when developing measures to prevent employees from developing an occupational disease.

Elevated Serum Titanium Levels in Children With Early Onset Scoliosis Treated With Growth-friendly Instrumentation.

BACKGROUND: A previous study showed significantly higher serum titanium levels in patients with early-onset scoliosis (EOS) treated with traditional growing rods (TGR) and magnetically controlled growing rods (MCGR) compared with controls. Children with vertical expandable prosthetic titanium rib (VEPTR) were not assessed. The purpose of this study was to compare serum titanium levels in EOS patients treated with TGR, MCGR, and VEPTR. We hypothesized that EOS patients treated with all forms of growth-friendly instrumentation (GFI) have elevated serum titanium levels. METHODS: This was a prospective cross-sectional case series. Serum titanium levels were collected from patients with GFI who were enrolled in an EOS database. Blood samples were collected at a clinic visit or lengthening/exchange procedure between April and December 2018. The normal range for serum titanium is 0 to 1 ng/mL. Analyses were conducted using analysis of variance and Bonferroni post hoc test. RESULTS: A total of 23 patients (2 TGR, 8 MCGR, 13 VEPTR) were analyzed. There was a significant difference in age at the time of blood sample collection (12.5 vs. 9.8 vs. 7.5 y, P=0.015) and serum titanium level (1.5 vs. 4.5 vs. 7.6 ng/mL, P=0.021) between TGR, MCGR, and VEPTR, respectively. All of the MCGR and VEPTR patients had a serum titanium level ≥2 ng/mL. Binary comparisons showed that VEPTR had a significantly higher serum titanium level than TGR (P=0.046). There was no difference in serum titanium level when MCGR was compared with TGR and VEPTR. Time from implant insertion to blood sample collection, number of rods currently implanted, total number of rods implanted throughout treatment, and number of lengthenings per patient was similar between the groups. CONCLUSIONS: Elevated serum titanium levels may be present in EOS patients treated with all forms of GFI. Although our TGR patients had indwelling implants for the longest period of time, they had the lowest serum titanium level. Repetitive chest wall motion during respiration may lead to continued wear and metal ion release with VEPTR. LEVEL OF EVIDENCE: Level II-therapeutic.

Derivation of whole blood biomonitoring equivalents for titanium for the interpretation of biomonitoring data.

Biomonitoring equivalents (BEs) have been increasingly applied for biomonitoring purposes by regulatory bodies worldwide. The present report describes the development of a BE for titanium based on a 4-step process: (i) identification of a critical study/point of departure (PoD) supporting an established oral exposure guidance value (OEGV);, (ii) review the available oral PK data and application of a pharmacokinetic model for titanium; (iii) selection of the most appropriate biomarker of exposure in a specific tissue and calculation of steady-state tissue levels corresponding to the PoD in the critical study; and (iv) derivation of BE value adjusting for the uncertainties considered in the original OEGV assessment. Using the above 4-step approach, a blood BE value of 32.5 µg titanium/L was derived. Key components of the analysis included a pharmacokinetic model developed by investigators at the Netherlands National Institute of Public Health (RIVM) and a two-year rodent bioassay of titanium conducted by the US National Cancer Institute. The most sensitive pharmacokinetic parameter involved in the current BE derivation is the oral absorption factor of 0.02%. The provisional BE proposed in this article may be updated as new information on the pharmacokinetics of titanium becomes available.

SEC hyphenated to a multielement-specific detector unravels the degradation pathway of a bimetallic anticancer complex in human plasma.

The bimetallic metal complex Titanocref exhibits relevant anticancer activity, but it is unknown if it is stable to reach target tissues intact. To gain insight, a pharmacologically relevant dose was added to human blood plasma and the mixture was incubated at 37 °C. The obtained mixture was analyzed 5 and 60 min later by size-exclusion chromatography hyphenated to an inductively coupled plasma atomic emission spectrometer (SEC-ICP-AES). We simultaneously detected several titanium (Ti), gold (Au) and sulfur (S)-peaks, which corresponded to a Ti degradation product that eluted partially, and a Au degradation product that eluted entirely bound to plasma proteins (both time points). Although ~70% of the intact Titanocref was retained on the column after 60 min, our results allowed us to establish - for the first time - its likely degradation pathway in human plasma at near physiological conditions. These results suggest that ~70% of Titanocref remain in plasma after 60 min, which supports results from a recent in vivo study in which mice were treated with Titanocref and revealed Ti:Au molar ratios in tumors and organs close to 1:1. Thus, our stability studies suggest that the intact drug is able to reach target tissue. Overall, our results exemplify that SEC-ICP-AES enables the execution of intermediate in vitro studies with human plasma in the context of advancing bimetallic metal-based drugs to more costly clinical studies.

Blood and plasma titanium levels associated with well-functioning hip implants.

BACKGROUND: Hip implants are usually manufactured from cobalt-chromium and titanium alloys. As the implants wear and corrode, metal debris is released into the surrounding tissue and blood, providing a potential biomarker for their function. Whilst there are laboratory reference levels for blood cobalt and chromium in patients with well and poorly functioning hip implants, there are no such guidelines for titanium. This is despite the increasing use of titanium implants worldwide. PATIENTS AND METHODS: We recruited a consecutive series of 95 patients (mean age 71 years, mean time after surgery 8.5 years) with one hip implant type, inserted by the same surgeon. We assessed clinical and radiological outcome, and measured blood and plasma titanium using high resolution inductively-coupled plasma mass spectrometry. RESULTS: The upper normal reference limit for blood and plasma titanium was 2.20 and 2.56 µg L-1, respectively, and did not differ significantly between males and females. CONCLUSION: We are the first to propose a laboratory reference level for blood and plasma titanium in patients with well-functioning titanium hip implants. This is an essential starting point for further studies to explore the clinical usefulness of blood titanium as a biomarker of orthopaedic implant performance, and comes at a time of considerable controversy regarding the use of certain titanium alloys in hip arthroplasty.

Challenges in the Measurement and Interpretation of Serum Titanium Concentrations.

The measurement of circulating metal ion levels in total hip arthroplasty patients continues to be an area of clinical interest. National regulatory agencies have recommended measurement of circulating cobalt and chromium concentrations in metal-on-metal bearing symptomatic total hip arthroplasty patients. However, the clinical utility of serum titanium (Ti) measurements is less understood due to wide variations in reported values and methodology. Fine-scale instrumentation for detecting in situ Ti levels continues to improve and has transitioned from graphite furnace atomic absorption spectroscopy to inductively coupled plasma optical emission spectrometry or inductively coupled plasma mass spectrometry. Additionally, analytical interferences, variable sample types, and non-standardized sample collection methods complicate Ti measurement and underlie the wide variation in reported levels. Normal reference ranges and pathologic ranges for Ti levels remain to be established quantitatively. However, before these ranges can be recognized and implemented, methodological standardization is necessary. This paper aims to provide background and recommendations regarding the complexities of measurement and interpretation of circulating Ti levels in total hip arthroplasty patients.

Blood titanium level as a biomarker of orthopaedic implant wear.

BACKGROUND: Joint replacement implants are usually manufactured from cobalt-chromium or titanium alloys. After the device is implanted, wear and corrosion generate metal particles and ions, which are released into local tissue and blood. The metal debris can cause a range of adverse local and systemic effects in patients. RESEARCH PROBLEM: In the case of cobalt and chromium, a blood level exceeding 7 µg L-1 indicates potential for local toxicity, and a failing implant. It has been repeatedly suggested in the literature that measurement of titanium could also be used to assess implant function. Despite an increasing interest in this biomarker, and growing use of titanium in orthopaedics, it is unclear what blood concentrations should raise concerns. This is partly due to the technical challenges involved in the measurement of titanium in biological samples. AIM: This Review summarises blood/serum titanium levels associated with well-functioning and malfunctioning prostheses, so that the prospects of using titanium measurements to gain insights into implant performance can be evaluated. CONCLUSION: Due to inter-laboratory analytical differences, reliable conclusions regarding "normal" and "abnormal" titanium levels in patients with orthopaedic implants are difficult to draw. Diagnosis of symptomatic patients should be based on radiographic evidence combined with blood/serum metal levels.

In vivo blood metal ion levels in patients after total shoulder arthroplasty.

BACKGROUND: Products from metal wear have been identified as a potential cause of adverse local tissue reactions and implant failure in total hip arthroplasty. However, the role of metal ion exposure in patients after total shoulder replacement is unclear. The objective of the present study was to determine in vivo blood metal ion levels of cobalt, chromium, and titanium in patients after anatomic total shoulder arthroplasty (TSA) or reverse TSA. METHODS: A consecutive series of patients after anatomic TSA or reverse TSA was evaluated retrospectively. After exclusion of patients with additional metal implants, 40 patients with unilateral anatomic TSA (n = 20) or reverse TSA (n = 20) were available for whole-blood metal ion analysis at a mean follow-up of 28 ± 9.6 months. Twenty-three healthy individuals without metal implants served as a control group. RESULTS: Mean cobalt ion concentrations were 0.18 µg/L (range, 0.1-0.66 µg/L), 0.15 µg/L (range, 0.03-0.48 µg/L), and 0.11 µg/L (range, 0.03-0.19 µg/L), mean chromium ion levels were 0.48 µg/L (range, 0.17-2.41 µg/L), 0.31 µg/L (range, 0.09-1.26 µg/L), and 0.14 µg/L (range, 0.04-0.99 µg/L), and mean titanium ion concentrations were 1.31 µg/L (range, 0.75-4.52 µg/L), 0.84 µg/L (range, 0.1-1.64 µg/L), and 0.62 µg/L (range, 0.32-2.14 µg/L) in the reverse TSA group, the anatomic TSA group, and the control group, respectively. CONCLUSIONS: TSA resulted in elevated metal ion levels compared with healthy controls, although overall metal ion concentrations measured in this study were relatively low. The role of local metal ion exposure in patients with total shoulder replacements should be further investigated.

Pulmonary impact of titanium dioxide nanorods: examination of nanorod-exposed rat lungs and human alveolar cells.

BACKGROUND: Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles. METHODS: In a combined in vitro-in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15×65 nm TiO2 nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg body-weight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods. RESULTS: Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO2-exposed rodents. CONCLUSION: Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats' lungs. Rod-shaped nanoparticulate TiO2 may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures.

Analysis of soluble or titanium dioxide derived titanium levels in human whole blood: consensus from an inter-laboratory comparison.

Exposure to titanium (Ti), via the ingestion of pigment grade Ti dioxide (TiO2), is commonplace for westernised populations. It may also occur as a consequence of metal ion leaching in subjects bearing Ti-containing implants. Accurate exposure analysis requires fit-for-purpose analytical methodology, especially for true measures of baseline levels. Inductively coupled plasma (ICP) techniques are, mainly, now used for bio-analysis of Ti. Since whole blood reference materials, certified for natural low levels of Ti, are not currently available, we undertook an inter-laboratory comparison of pooled human blood from fasted volunteers ±low level (+∼2.5 µg L-1) or high level (+10-20 µg L-1) spikes of soluble Ti or TiO2 particles. Seven established laboratories were enrolled to analyse the samples using ICP based techniques, which included at least one of ICP optical emission spectrometry (ICP-OES), high resolution ICP mass spectrometry (HR-ICP-MS), triple quadrupole ICP-MS (ICP-MS/MS) or single quadrupole ICP-MS (SQ-ICP-MS). Five laboratories diluted the blood for analysis whilst two performed acid digestion. Overall, we showed that the laboratories could, mostly, quantitatively detect modest levels of spiked Ti in blood. Markedly varying levels of Ti, however, were reported for the same baseline pooled sample (0.4-24.6 µg L-1) and, in this study, specificity was poor for SQ-ICP-MS. Digestion of samples caused sample contamination compromising limits of detection and accuracy, whilst simple dilution had no such problem, and remained linear in response for spikes with ionic and TiO2 particles. We conclude that measuring baseline levels of Ti in whole blood is challenging but should be readily achievable down to 0.5-1.5 µg L-1, if sample preparation avoids contamination and instrument techniques are used that negate polyatomic or isobaric interferences from the sample matrix. We also remind those relying upon Ti bio-analytical data for their experimental outcomes that (a) spiking and recovery experiments provide information only on linearity of detection but not at all on accuracy as this will not detect constant positive errors and that (b) biological standard materials for Ti generally contain high levels of the analyte and tend to mask baseline analytical errors. Caution may be required in interpreting the findings of some published Ti/TiO2 bio-exposure studies.

Evaluation of Blood Titanium Levels and Total Bone Contact Area of Dental Implants.

The purpose of this study was to evaluate the effect of total implant-bone surface contact area of dental implants applied on partial or total edentulous patients on the increase in the level of blood titanium level. Changes of the blood titanium levels were evaluated after placement of the dental implants in 30 patients including 15 females and 15 males. Patients were divided into 3 groups as dental implants were applied on only maxilla, only mandible, or both of them. Taking into the consideration anatomic formation and prosthetic indication, dental implant-bone total contact area was calculated and saved for each patient after dental implants placement. Blood samples of the patients taken preoperatively and postoperatively at 12 weeks were analyzed by ICP-MS device. Blood titanium levels of preoperative and postoperative blood samples were analyzed for each patient and results were evaluated statistically. In the evaluation after analyzing blood titanium level changes, while a statistically significant decrease was observed in Group 1 patients, a statistically significant increase was observed in Group 2 and Group 3 patients to blood titanium level. A statistically significant difference was observed between Group 1 and Group 2 and between Group 1 and Group 3 patients of blood titanium levels. The change of the blood titanium level was not related to total implant-bone surface area, number of the implants, and gender. In our study, no correlation was found between change of blood titanium level and total contact area with bone of dental implants. We believe that more accurate results can be obtained with biopsy of tissues and organs on animal studies.

Surface integrity of polyethylene liners following trunnionosis of a dual modular neck total hip implant.

BACKGROUND: There has been a trend in the evolution of total hip arthroplasty towards increased modularity; with this increase in modularity come some potentially harmful consequences. Modularity at the neck shaft junction has been linked to corrosion, adverse reaction to metal debris and pseudotumour formation. AIM: The aim of this retrieval study is to assess whether the surface integrity of the polyethylene (PE) liner is affected by metal wear debris in a single implant design series of THA revised for trunnionosis. METHODS: A retrieval analysis of thirty dual-taper modular neck hip prostheses was performed; the mean time from implantation to revision was 2.7 years (1.02-6.2). PE liners were analysed using a scanning electron microscope with an energy dispersive spectrometer to assess for metal particles embedded on the liner surface. Serum metal ion levels and inflammatory markers were also analysed. RESULTS: There were small numbers of metal particles present on the PE liners. The mean number of metal particles per liner was four and the particles varied in size from 0.5 µm to 122 µm mean 16 µm. All patients had elevated metal ion levels: cobalt 6.02 µg/l, chromium 1.22 µg/l, titanium 3.11 µg/l. The cobalt:chromium ratio was 7.55:1. Inflammatory markers were also marginally raised (ESR 17; CRP 10). CONCLUSION: These results suggest that retention of PE liners may be reasonable when performing isolated revision of the femoral component in cases of failure at the modular neck stem junction, especially when the inner diameter of the liner is already optimised for head size and stability.

Association between periprosthetic tissue metal content, whole blood and synovial fluid metal ion levels and histopathological findings in patients with failed metal-on-metal hip replacement.

Adverse Reaction to Metal Debris (ARMD) is a major cause of implant failure leading to revision surgery in patients with metal-on-metal (MoM) hip arthroplasties. However, the pathogenesis and its association to implant wear are poorly understood and previous studies have yielded discrepant results. We sought to investigate the associations between histological findings, whole blood and synovial fluid metal ion concentrations and periprosthetic tissue metal concentrations in patients with MoM total hip replacements and hip resurfacings revised for ARMD. 107 hips in total were included in our study. Of these, 87 were total hip replacements and 20 were hip resurfacings, respectively. We found that whole blood, synovial fluid and periprosthetic tissue metal concentrations correlated poorly with histological findings. We suggest that the lack of a clear association between histological findings and wear measures in the present study as well as in previous studies is mostly influenced by variability in patient susceptibility. However, patients presenting with perivascular lymphocytic infiltration had lower chromium concentration in their periprosthetic tissues than patients with no perivascular lymphocytic infiltration. This may reflect the role of metal hypersensitivity in implant failure in these patients. Patients with total hip replacements evinced more necrosis and lymphocytic infiltration in their tissues than patients with hip resurfacings. This suggests that trunnion wear debris is more cytotoxic and/or immunogenic than bearing wear debris leading to higher failure rates seen in patients with total hip replacements.

Serum Metal Levels in Maxillofacial Reconstructive Surgery Patients: A Pilot Study.

PURPOSE: The aim of this pilot study was to assay metal concentrations in the serum of patients who had undergone dental implant placement, orthognathic surgery using rigid metal fixation plates and screws, and total temporomandibular joint replacement (TMJ TJR). MATERIALS AND METHODS: Thirty patients were identified and included in this pilot study. Sixteen patients (9 men and 8 women), with an average age of 44 years (range, 19 to 79 yr), provided informed consent to participate and were divided into 3 study groups with 4 patients in each (group 1, orthognathic surgery; group 2, TMJ TJR; and group 3, dental implant placement). A control group consisted of volunteers without any implanted metallic devices. Blood samples for serum metal analysis were obtained and analyzed in accordance with the standardized collection and testing protocols used at the Trace Metal Analysis Laboratory of the Department of Orthopedic Surgery at the Rush University Medical Center (Chicago, IL). RESULTS: All control participants had levels below the normal reference range for all serum markers assessed. In the orthognathic group, 1 patient had an increased serum cobalt level. In the TMJ TJR group, 1 patient had an increased serum cobalt level and another patient had an increased serum chromium level. In the dental implant group, 1 patient had an increased serum titanium level and another had increased serum levels of titanium and chromium. CONCLUSIONS: This is the first study to report on the release of metal into the bloodstream in patients with different maxillofacial implanted metallic objects. The results raise questions regarding the types and magnitude of metal released from maxillofacial reconstruction devices and their potential long-term local and systemic effects. Future large-scale prospective studies involving serial measurements in homogeneous groups of patients could further elucidate the impact of these findings.