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The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 94 - 99
1 Jan 2007
Bottner F Wegner A Winkelmann W Becker K Erren M Götze C

This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement. The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-α were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis. C-reactive protein (> 3.2 md/dl) and interleukin-6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 vs 0.96). Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant. Procalcitonin (> 0.3 ng/ml) and TNF-α (> 40 ng/ml) are very specific (0.98 vs 0.94) but have a low sensitivity (0.33 vs 0.43). The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 311 - 320
1 Mar 2022
Cheok T Smith T Siddiquee S Jennings MP Jayasekera N Jaarsma RL

Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results. Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion. Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 6 | Pages 912 - 917
1 Aug 2004
Beeton CA Chatfield D Brooks RA Rushton N

There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) in serum from patients who had sustained a head injury with and without fracture and compared these with levels found in control subjects. Within 12 hours of injury the serum level of IL-6 was significantly higher in patients with head injury and fracture compared with the control group. Levels of IL-6 were also significantly higher in patients with head injury and fracture compared with fracture only. While there was no significant difference in circulating levels of sIL-6R in the initial samples they were increased one week after surgery in patients with head injury and fracture and with head injury only. In addition, reduced levels of sgp130 in patients with head injury with and without fracture indicated a possible reduction of the inhibitory effect of this protein on the activity of IL-6. Our study suggests that IL-6 may be involved in altered healing of a fracture after head injury


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 71 - 75
1 Jan 2015
Hoell S Borgers L Gosheger G Dieckmann R Schulz D Gerss J Hardes J

The purpose of this study was to evaluate whether the serum level of interleukin 6 (IL-6) could be used to identify the persistence of infection after the first stage of a two-stage revision for periprosthetic joint infection.

Between 2010 and 2011, we prospectively studied 55 patients (23 men, 32 women; mean age 69.5 years; 36 to 86) with a periprosthetic joint infection. Bacteria were identified in two intra-operative tissue samples during re-implantation in 16 patients. These cases were classified as representing persistent infection.

To calculate a precise cut-off value which could be used in everyday clinical practice, a 3 x 2 contingency table was constructed and manually defined.

We found that a serum IL-6 ≥ 13 pg/mL can be regarded as indicating infection: its positive-predictive value is 90.9%. A serum IL-6 ≤ 8 pg/mL can be regarded as indicating an absence of infection: its negative predictive value is 92.1%.

The serum IL-6 level seems to be a reasonable marker for identifying persistent infection after the first stage of a revision joint arthroplasty and before attempting re-implantation.

Cite this article: Bone Joint J 2015;97-B:71–5.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 8 | Pages 1118 - 1122
1 Aug 2010
Lee JS Suh KT Eun IS

Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes.

These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS.


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 113 - 122
1 Jan 2021
Kayani B Tahmassebi J Ayuob A Konan S Oussedik S Haddad FS

Aims. The primary aim of this study was to compare the postoperative systemic inflammatory response in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic-arm assisted total knee arthroplasty (robotic TKA). Secondary aims were to compare the macroscopic soft tissue injury, femoral and tibial bone trauma, localized thermal response, and the accuracy of component positioning between the two treatment groups. Methods. This prospective randomized controlled trial included 30 patients with osteoarthritis of the knee undergoing conventional TKA versus robotic TKA. Predefined serum markers of inflammation and localized knee temperature were collected preoperatively and postoperatively at six hours, day 1, day 2, day 7, and day 28 following TKA. Blinded observers used the Macroscopic Soft Tissue Injury (MASTI) classification system to grade intraoperative periarticular soft tissue injury and bone trauma. Plain radiographs were used to assess the accuracy of achieving the planned postioning of the components in both groups. Results. Patients undergoing conventional TKA and robotic TKA had comparable changes in the postoperative systemic inflammatory and localized thermal response at six hours, day 1, day 2, and day 28 after surgery. Robotic TKA had significantly reduced levels of interleukin-6 (p < 0.001), tumour necrosis factor-α (p = 0.021), ESR (p = 0.001), CRP (p = 0.004), lactate dehydrogenase (p = 0.007), and creatine kinase (p = 0.004) at day 7 after surgery compared with conventional TKA. Robotic TKA was associated with significantly improved preservation of the periarticular soft tissue envelope (p < 0.001), and reduced femoral (p = 0.012) and tibial (p = 0.023) bone trauma compared with conventional TKA. Robotic TKA significantly improved the accuracy of achieving the planned limb alignment (p < 0.001), femoral component positioning (p < 0.001), and tibial component positioning (p < 0.001) compared with conventional TKA. Conclusion. Robotic TKA was associated with a transient reduction in the early (day 7) postoperative inflammatory response but there was no difference in the immediate (< 48 hours) or late (day 28) postoperative systemic inflammatory response compared with conventional TKA. Robotic TKA was associated with decreased iatrogenic periarticular soft tissue injury, reduced femoral and tibial bone trauma, and improved accuracy of component positioning compared with conventional TKA. Cite this article: Bone Joint J 2021;103-B(1):113–122


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 46 - 55
1 Jan 2021
Grzelecki D Walczak P Szostek M Grajek A Rak S Kowalczewski J

Aims. Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). Methods. Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. Results. Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. Conclusion. This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46–55


Aims. Intravenous dexamethasone has been shown to reduce immediate postoperative pain after total hip arthroplasty (THA), though the effects are short-lived. We aimed to assess whether two equivalent perioperative split doses were more effective than a single preoperative dose. Methods. A total of 165 patients were randomly assigned into three groups: two perioperative saline injections (Group A, placebo), a single preoperative dose of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative doses of 10 mg dexamethasone (Group C). Patients, surgeons, and staff collecting outcome data were blinded to allocation. The primary outcome was postoperative pain level reported on a ten-point Numerical Rating Scale (NRS) at rest and during activity. The use of analgesic and antiemetic rescue, incidence of postoperative nausea and vomiting (PONV), CRP and interleukin-6 (IL-6) levels, range of motion (ROM), length of stay (LOS), patient satisfaction, and the incidence of surgical site infection (SSI) and gastrointestinal bleeding (GIB) in the three months postoperatively, were also compared. Results. The pain scores at rest were significantly lower in Groups B and C than in Group A on postoperative days 1 and 2. The dynamic pain scores and CRP and IL-6 levels were significantly lower for Groups B and C compared to Group A on postoperative days 1, 2, and 3. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, improved ROM, shorter LOS, and reported higher satisfaction than in Group A. Patients in Group C had significantly lower dynamic pain scores and IL-6 and CRP levels on postoperative days 2 and 3, and higher ROM and satisfaction on postoperative day 3 than in Group B. No SSI or GIB occurred in any group. Conclusion. Perioperative dexamethasone provides short-term advantages in reducing pain, PONV, and inflammation, and increasing range of motion in the early postoperative period after THA. A split-dose regimen was superior to a single high dose in reducing pain and inflammation, and increasing ROM, with better patient satisfaction. Level of evidence: I. Cite this article: Bone Joint J 2020;102-B(11):1497–1504


Aims. The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA). Patients and Methods. A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE). Results. The mean HBL was significantly lower in group C (402.13 ml standard deviation (. sd). 225.97) than group A (679.28 ml. sd. 277.16, p < 0.001) or B (560.62 ml . sd. 295.22, p = 0.010). The decrease in the level of Hb between the pre-operative baseline and the level on the third post-operative day was 30.82 g/L (. sd. 6.31 g/L) in group A, 27.16 g/L (. sd. 6.83) in group B and 21.98 g/L (. sd. 3.72) in group C. This decrease differed significantly among the three groups (p < 0.01). The mean level of CRP was significantly lower in group C than in the other two groups on the second (p ≤ 0.034) and third post-operative days (p ≤ 0.014). The levels of IL-6 were significantly lower in group C than group A on the first three post-operative days (p = 0.023). The mean length of stay was significantly lower in group C than group A (p = 0.023). No VTE or other adverse events occurred. Conclusion. Multiple boluses of IV-TXA can effectively reduce HBL following primary THA. A regime of three boluses leads to a smaller decrease in the level of Hb, less post-operative inflammation and a shorter length of stay in hospital than a single bolus. Cite this article: Bone Joint J 2017;99-B:1442–9


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 3 | Pages 393 - 399
1 Mar 2008
Morley JR Smith RM Pape HC MacDonald DA Trejdosiewitz LK Giannoudis PV

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming. In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open. In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1065 - 1070
1 Aug 2011
Tanavalee A Honsawek S Rojpornpradit T Sakdinakiattikoon M Ngarmukos S

We compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery. Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p < 0.001) and functional score (p < 0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml (. sd. 53.4) versus 201 pg/ml (. sd. 49.4) for groups I and II, respectively) and CRP (91 mg/L (. sd. 24.1) versus 88 mg/L (. sd. 23.4), respectively) on the first post-operative day, returning to pre-operative values at two and six weeks, respectively. The mean peak level of ESR for the respective two groups was 46 mm/hr versus 48 mm/hr at two weeks, which had still not returned to its pre-operative mean value at 26 weeks. The elevation in the skin temperature appeared to mirror the peak elevation of the ESR, with a range of 2.5° C to 4.5° C with some reduction at 26 weeks but still exceeding the pre-operative value. We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery


The Bone & Joint Journal
Vol. 103-B, Issue 12 | Pages 1745 - 1753
1 Dec 2021
Walinga AB Stornebrink T Langerhuizen DWG Struijs PAA Kerkhoffs GMMJ Janssen SJ

Aims

This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint?

Methods

We performed a search of PubMed, Embase, and Cochrane libraries for relevant studies published between January 1980 and April 2020. Of 3,209 identified studies, we included 27 after full screening. Sensitivity, specificity, area under the curve, and Youden index of diagnostic tests were extracted from included studies. We grouped test characteristics per diagnostic modality. We extracted the definitions used to establish a definitive diagnosis of bacterial arthritis of a native joint per study.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 6 | Pages 920 - 930
1 Aug 2002
Liagre B Moalic S Vergne P Charissoux JL Bernache-Assollant D Beneytout JL

We describe a model which can be used for in vitro biocompatibility assays of biomaterials. We studied the in vitro response of human osteoarthritis or rheumatoid arthritis fibroblast-like synoviocytes to Al. 2. O. 3. or ZrO. 2. particles by analyzing the production of interleukin-1 (IL-1) and interleukin-6 (IL-6) and the metabolism of arachidonic acid via lipoxygenase and cyclo-oxygenase pathways. Our results show that, in these cells and under our experimental conditions, Al. 2. O. 3. and ZrO. 2. did not significantly modify the synthesis of IL-1 and IL-6 or the metabolism of arachidonic acid


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 2 | Pages 278 - 282
1 Mar 2001
Wimhurst JA Brooks RA Rushton N

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO. 4. , Palacos R with ZrO. 2. and from CMW3 which contains BaSO. 4. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 5 | Pages 759 - 770
1 Jul 2004
Vermes C Chandrasekaran R Dobai JG Jacobs JJ Andersson GBJ An H Hallab NJ Galante JO Glant TT

Periprosthetic bone loss after total joint arthroplasty is a major clinical problem resulting in aseptic loosening of the implant. Among many cell types, osteoblasts play a crucial role in the development of peri-implant osteolysis. In this study, we tested the effects of calcitriol (1α,25-dihydroxy-vitamin-D. 3. ) and the bisphosphonate pamidronate on titanium-particle- and TNF-α-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. We monitored the expression of procollagen α1[1], osteocalcin, osteonectin and alkaline phosphatase mRNAs by Northern blots and real-time reverse transcription and polymerase chain reaction analyses. The release of various cytokines was also analysed by ELISA. We found that calcitriol or pamidronate could only partially recover the altered functions of osteoblasts when added alone. Only a combination of these compounds restored all the tested functions of osteoblasts. The local delivery of these drugs may have therapeutic potential to prevent or to treat periprosthetic osteolysis and aseptic loosening of implants


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 2 | Pages 196 - 201
1 Mar 2002
Burke JG Watson RWG McCormack D Dowling FE Walsh MG Fitzpatrick JM

Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E. 2. (PGE. 2. ) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 2 | Pages 356 - 361
1 Mar 1999
Giannoudis PV Smith RM Bellamy MC Morrison JF Dickson RA Guillou PJ

It has been suggested that reamed intramedullary nailing of the femur should be avoided in some patients with multiple injuries. We have studied prospectively the effect of femoral reaming on the inflammatory process as implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6) (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s-ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion molecules) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by nailing. We have also compared reamed nailing with unreamed nailing. We found that the levels of serum IL-6 and elastase rose significantly during the nailing procedure indicating a measurable ‘second hit’. There was no clear response in leukocyte activation and no difference in the release of endothelial adhesion molecule markers. There was no significant difference between groups treated by reamed and unreamed nailing. Although clinically unremarkable, the one patient who died from ARDS was shown to be hyperstimulated after injury and again after nailing, suggesting the importance of an excessive inflammatory reaction in the pathogenesis of these serious problems. Our findings have shown that there is a second hit associated with femoral nailing and suggest that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 2 | Pages 311 - 315
1 Mar 1997
Rogers SD Howie DW Graves SE Pearcy MJ Haynes DR

Our aim was to determine whether in vitro studies would detect differences in the cellular response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 μm in diameter representative of those found adjacent to failed prostheses. Exposure of human monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10. 7. particles/ml produced a mean prostaglandin E. 2. release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 448 - 458
1 Apr 2001
Jones LC Frondoza C Hungerford DS

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this. We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks. The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss. Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 234 - 244
1 Feb 2021
Gibb BP Hadjiargyrou M

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics.

Cite this article: Bone Joint J 2021;103-B(2):234–244.