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Bone & Joint Research
Vol. 8, Issue 1 | Pages 11 - 18
1 Jan 2019
McLean M McCall K Smith IDM Blyth M Kitson SM Crowe LAN Leach WJ Rooney BP Spencer SJ Mullen M Campton JL McInnes IB Akbar M Millar NL

Objectives. Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods. Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results. There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion. The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations. Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11–18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1


Bone & Joint Research
Vol. 10, Issue 6 | Pages 348 - 350
1 Jun 2021
Skinner JA Sabah SA Hart AJ


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842


Bone & Joint Research
Vol. 13, Issue 11 | Pages 632 - 646
7 Nov 2024
Diaz Dilernia F Watson D Heinrichs DE Vasarhelyi E

Aims. The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against Staphylococcus aureus. Methods. We performed in vitro growth and viability assays to determine the capability of S. aureus to survive in SF with the addition of 10 µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated its sensitivity to killing, comparing wild type (WT) and CopAZB-deficient USA300 strains. Results. UAMS-1 demonstrated a greater sensitivity to SF compared to USA300 WT at 12 hours (p = 0.001) and 24 hours (p = 0.027). UAMS-1 died in statistically significant quantities at 24 hours (p = 0.017), and USA300 WT survived at 24 hours. UAMS-1 was more susceptible to the addition of copper at four (p = 0.001), 12 (p = 0.005), and 24 hours (p = 0.006). We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at four (p = 0.011), 12 (p = 0.011), and 24 hours (p = 0.011). WT and CopAZB-deficient USA300 strains significantly died in SF, demonstrating a MBC-Cu of 50 µM against USA300 WT (p = 0.011). Conclusion. SF has antimicrobial properties against S. aureus, and UAMS-1 was more sensitive than USA300 WT. Adding 10 µM of copper was highly toxic, confirming its bactericidal effect. We found CopAZB proteins to be involved in copper effluxion by demonstrating the high sensitivity of mutant strains to lower copper concentrations. Thus, we propose CopAZB proteins as potential targets and use exogenous copper as a treatment alternative against S. aureus. Cite this article: Bone Joint Res 2024;13(11):632–646


Bone & Joint Research
Vol. 8, Issue 2 | Pages 41 - 48
1 Feb 2019
Busse P Vater C Stiehler M Nowotny J Kasten P Bretschneider H Goodman SB Gelinsky M Zwingenberger S

Objectives. Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. Methods. Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. Results. Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. Conclusion. The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability. Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41–48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1


Aims. In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models. Methods. The cell toxicity of different concentrations of EDTA dissolved in NS (EDTA-NS) was assessed by Cell Counting Kit-8 (CCK-8). Various concentrations of EDTA-NS irrigation solution were compared in three female Sprague-Dawley rat models: 1) a skin defect; 2) a bone exposed; and 3) a wound with an intra-articular implant. All three models were contaminated with Staphylococcus aureus or Escherichia coli. EDTA was dissolved at a concentration of 0 (as control), 0.1, 0.5, 1, 2, 5, 10, 50, and 100 mM in sterile NS. Samples were collected from the wounds and cultured. The bacterial culture-positive rate (colony formation) and infection rate (pus formation) of each treatment group were compared after irrigation and debridement. Results. Cell viability intervened below 10 mM concentrations of EDTA-NS showed no cytotoxicity. Concentrations of 1, 2, and 5 mM EDTA-NS had lower rates of infection and positive cultures for S. aureus and E. coli compared with other concentrations in the skin defect model. For the bone exposed model, 0.5, 1, and 2 mM EDTA-NS had lower rates of infection and positive cultures. For intra-articular implant models 10 and 50 mM, EDTA-NS had the lowest rates of infection and positive cultures. Conclusion. The concentrations of EDTA-NS below 10 mM are safe for irrigation. The optimal concentration of EDTA-NS varies by type of wound after experimental inoculation of three types of wound. Cite this article: Bone Joint Res 2021;10(1):68–76


Bone & Joint Research
Vol. 6, Issue 12 | Pages 649 - 655
1 Dec 2017
Liu Y Zhu H Hong H Wang W Liu F

Objectives. Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co. 2+. ) during wear of MOM hip implants, but the toxic mechanism is not clear. Methods. To evaluate the protective effect of zinc ions (Zn. 2+. ), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn. 2+. for four hours. The cells were then exposed to different concentrations of CoNPs and Co. 2+. for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured. Results. CoNPs and Co. 2+. can induce the increase of ROS and inflammatory cytokines, such as tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, Zn pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co. 2+. , decrease ROS production, and decrease levels of inflammatory cytokines in Balb/3T3 mouse fibroblast cells. Conclusion. These results suggest that Zn pretreatment can provide protection against inflammation and cytotoxicity induced by CoNPs and Co. 2+. in Balb/3T3 cells. Cite this article: Y. Liu, H. Zhu, H. Hong, W. Wang, F. Liu. Can zinc protect cells from the cytotoxic effects of cobalt ions and nanoparticles derived from metal-on-metal joint arthroplasties? Bone Joint Res 2017;6:649–655. DOI: 10.1302/2046-3758.612.BJR-2016-0137.R2


Bone & Joint Research
Vol. 4, Issue 5 | Pages 70 - 77
1 May 2015
Gupta A Liberati TA Verhulst SJ Main BJ Roberts MH Potty AGR Pylawka TK El-Amin III SF

Objectives. The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. Methods. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. Results. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Conclusions. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70–7


Bone & Joint Research
Vol. 8, Issue 2 | Pages 81 - 89
1 Feb 2019
Funk GA Menuey EM Cole KA Schuman TP Kilway KV McIff TE

Objectives. The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content. Methods. Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties. Results. Compared with control, the rifampin-incorporated cement had a prolonged setting time and a reduction in exothermic output during polymerization. The rifampin cement showed significantly reduced strength and was below the orthopaedic weight-bearing threshold of 70 MPa. Based on the radical scavenging assay and strength tests, the hydroquinone structure within rifampin was identified as the polymerization inhibitor. Conclusion. The incorporation of rifampin into PMMA bone cement interferes with the cement’s radical polymerization. This interference is due to the hydroquinone moiety within rifampin. This combination alters the cement’s handling and curing properties, and lowers the strength below the threshold for weight-bearing applications. Additionally, the incomplete polymerization leads to increased toxic monomer output, which discourages its use even in non-weight-bearing applications. Cite this article: G. A. Funk, E. M. Menuey, K. A. Cole, T. P. Schuman, K. V. Kilway, T. E. McIff. Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement. Bone Joint Res 2019;8:81–89. DOI: 10.1302/2046-3758.82.BJR-2018-0170.R2


Bone & Joint Research
Vol. 8, Issue 2 | Pages 49 - 54
1 Feb 2019
Stravinskas M Nilsson M Vitkauskiene A Tarasevicius S Lidgren L

Objectives. The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month. Methods. Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine. Results. The antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively. Conclusion. This is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection. Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49–54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2


Bone & Joint Research
Vol. 5, Issue 10 | Pages 461 - 469
1 Oct 2016
Liu YK Deng XX Yang H

Objectives. The cytotoxicity induced by cobalt ions (Co. 2+. ) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co. 2+. and Co-NPs on liver cells, and explain further the potential mechanisms. Methods. Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co. 2+. or Co-NPs treatment. Results. Results showed cytotoxic effects of Co. 2+. and Co-NPs were dependent upon time and dosage, and the cytotoxicity of Co-NPs was greater than that of Co. 2+. In addition, Co-NPs elicited a significant (p < 0.05) reduction in cell viability with a concomitant increase in lactic dehydrogenase release, reactive oxygen species generation, IL-8 mRNA expression, Bax/Bcl-2 mRNA expression and DNA damage after 24 hours of exposure. Conclusion. Co-NPs induced greater cytotoxicity and genotoxicity in BRL-3A cells than Co. 2+. Cell membrane damage, oxidative stress, immune inflammation and DNA damage may play an important role in the effects of Co-NPs on liver cells. Cite this article: Y. K. Liu, X. X. Deng, H.L. Yang. Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions. Bone Joint Res 2016;5:461–469. DOI: 10.1302/2046-3758.510.BJR-2016-0016.R1


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 729 - 734
1 Jul 2023
Borghi A Gronchi A

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 535 - 545
2 Oct 2024
Zou C Guo W Mu W Wahafu T Li Y Hua L Xu B Cao L

Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Methods

We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Methods

The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites.


Bone & Joint Open
Vol. 4, Issue 7 | Pages 516 - 522
10 Jul 2023
Mereddy P Nallamilli SR Gowda VP Kasha S Godey SK Nallamilli RR GPRK R Meda VGR

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Methods

Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30).


Bone & Joint Research
Vol. 13, Issue 10 | Pages 525 - 534
1 Oct 2024
Mu W Xu B Wang F Maimaitiaimaier Y Zou C Cao L

Aims

This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

Methods

We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Methods

A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Methods

A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 412 - 422
4 Jul 2023
Ferguson J Bourget-Murray J Hotchen AJ Stubbs D McNally M

Aims

Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

Methods

A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Methods

The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 40 - 51
11 Jan 2024
Lin J Suo J Bao B Wei H Gao T Zhu H Zheng X

Aims

To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

Methods

EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Methods

HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Methods

A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4).


Bone & Joint Open
Vol. 4, Issue 4 | Pages 219 - 225
1 Apr 2023
Wachtel N Meyer E Volkmer E Knie N Lukas B Giunta R Demmer W

Aims

Wrist arthroscopy is a standard procedure in hand surgery for diagnosis and treatment of wrist injuries. Even though not generally recommended for similar procedures, general administration of perioperative antibiotic prophylaxis (PAP) is still widely used in wrist arthroscopy.

Methods

A clinical ambispective dual-centre study was performed to determine whether PAP reduces postoperative infection rates after soft tissue-only wrist arthroscopies. Retrospective and prospective data was collected at two hospitals with departments specialized in hand surgery. During the study period, 464 wrist arthroscopies were performed, of these 178 soft-tissue-only interventions met the study criteria and were included. Signs of postoperative infection and possible adverse drug effects (ADEs) of PAP were monitored. Additionally, risk factors for surgical site infection (SSIs), such as diabetes mellitus and BMI, were obtained.


Bone & Joint Research
Vol. 11, Issue 12 | Pages 854 - 861
1 Dec 2022
Park TJ Park SY Cho W Oh H Lee HJ Abd El-Aty AM Bayram C Jeong JH Jung TW

Aims

Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear.

Methods

Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 580 - 589
20 Sep 2023
Dai X Liu B Hou Q Dai Q Wang D Xie B Sun Y Wang B

Aims

The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

Methods

In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 628 - 635
22 Aug 2023
Hedlundh U Karlsson J Sernert N Haag L Movin T Papadogiannakis N Kartus J

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

Methods

A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 304 - 311
15 Apr 2024
Galloway R Monnington K Moss R Donaldson J Skinner J McCulloch R

Aims

Young adults undergoing total hip arthroplasty (THA) largely have different indications for surgery, preoperative function, and postoperative goals compared to a standard patient group. The aim of our study was to describe young adult THA preoperative function and quality of life, and to assess postoperative satisfaction and compare this with functional outcome measures.

Methods

A retrospective cohort analysis of young adults (aged < 50 years) undergoing THA between May 2018 and May 2023 in a single tertiary centre was undertaken. Median follow-up was 31 months (12 to 61). Oxford Hip Score (OHS) and focus group-designed questionnaires were distributed. Searches identified 244 cases in 225 patients. Those aged aged under 30 years represented 22.7% of the cohort. Developmental dysplasia of the hip (50; 45.5%) and Perthes’ disease (15; 13.6%) were the commonest indications for THA.


Aims

This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

Methods

A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 189 - 198
7 Mar 2023
Ruiz-Fernández C Ait Eldjoudi D González-Rodríguez M Cordero Barreal A Farrag Y García-Caballero L Lago F Mobasheri A Sakai D Pino J Gualillo O

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

Methods

We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.


Aims

Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

Methods

Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Methods

Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.


Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Methods

Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 103 or 1 × 106 colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 103 or 1 × 106 CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash.


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 601 - 614
21 Sep 2023
Gu P Pu B Liu T Yue D Xin Q Li H Yang B Ke D Zheng X Zeng Z Zhang Z

Aims

Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Methods

PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 647 - 658
12 Nov 2024
Li K Zhang Q

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

Methods

A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Methods

CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Open
Vol. 3, Issue 5 | Pages 348 - 358
1 May 2022
Stokes S Drozda M Lee C

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.


Aims

Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

Methods

Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.


Bone & Joint Open
Vol. 3, Issue 7 | Pages 529 - 535
1 Jul 2022
Wormald JCR Rodrigues JN Cook JA Prieto-Alhambra D Costa ML

Aims

Hand trauma accounts for one in five of emergency department attendances, with a UK incidence of over five million injuries/year and 250,000 operations/year. Surgical site infection (SSI) in hand trauma surgery leads to further interventions, poor outcomes, and prolonged recovery, but has been poorly researched. Antimicrobial sutures have been recognized by both the World Health Organization and the National Institute for Clinical Excellence as potentially effective for reducing SSI. They have never been studied in hand trauma surgery: a completely different patient group and clinical pathway to previous randomized clinical trials (RCTs) of these sutures. Antimicrobial sutures are expensive, and further research in hand trauma is warranted before they become standard of care. The aim of this protocol is to conduct a feasibility study of antimicrobial sutures in patients undergoing hand trauma surgery to establish acceptability, compliance, and retention for a definitive trial.

Methods

A two-arm, multicentre feasibility RCT of 116 adult participants with hand and wrist injuries, randomized to either antimicrobial sutures or standard sutures. Study participants and outcome assessors will be blinded to treatment allocation. Outcome measures will be recorded at baseline (preoperatively), 30 days, 90 days, and six months, and will include SSI, patient-reported outcome measures, and return to work.


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1082 - 1088
1 Dec 2021
Hippalgaonkar K Chandak V Daultani D Mulpur P Eachempati KK Reddy AG

Aims

Single-shot adductor canal block (ACB) after total knee arthroplasty (TKA) for postoperative analgesia is a common modality. Patients can experience breakthrough pain when the effect of ACB wears off. Local anaesthetic infusion through an intra-articular catheter (IAC) can help manage breakthrough pain after TKA. We hypothesized that combined ACB with ropivacaine infusion through IAC is associated with better pain relief compared to ACB used alone.

Methods

This study was a prospective double-blinded placebo-controlled randomized controlled trial to compare the efficacy of combined ACB+ IAC-ropivacaine infusion (study group, n = 68) versus single-shot ACB+ intra-articular normal saline placebo (control group, n = 66) after primary TKA. The primary outcome was assessment of pain, using the visual analogue scale (VAS) recorded at 6, 12, 24, and 48 hours after surgery. Secondary outcomes included active knee ROM 48 hours after surgery and additional requirement of analgesia for breakthrough pain.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 284 - 290
1 Apr 2022
O'Hara NN Carullo J Joshi M Banoub M Claeys KC Sprague S Slobogean GP O'Toole RV

Aims

There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients.

Methods

This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 200 - 209
1 Apr 2022
Liu YD Liu JF Liu B

Aims

The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development.

Methods

Diabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot.


Bone & Joint Open
Vol. 2, Issue 10 | Pages 785 - 795
1 Oct 2021
Matar HE Porter PJ Porter ML

Aims

Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA).

Methods

Studies were identified by searching electronic databases: Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Embase, from their inception to November 2020, for studies evaluating TKA patients with metal hypersensitivity/allergy. All studies reporting on diagnosing or managing metal hypersensitivity in TKA were included. Data were extracted and summarized based on study design, study population, interventions and outcomes. A practical guide is then formulated based on the available evidence.


Bone & Joint Open
Vol. 3, Issue 1 | Pages 61 - 67
18 Jan 2022
van Lingen CP Ettema HB Bosker BH Verheyen CCPM

Aims

Large-diameter metal-on-metal (MoM) total hip arthroplasty (THA) has demonstrated unexpected high failure rates and pseudotumour formation. The purpose of this prospective cohort study is to report ten-year results in order to establish revision rate, prevalence of pseudotumour formation, and relation with whole blood cobalt levels.

Methods

All patients were recalled according to the guidelines of the Dutch Orthopaedic Association. They underwent clinical and radiographical assessments (radiograph and CT scan) of the hip prosthesis and whole blood cobalt ion measurements. Overall, 94 patients (95 hips) fulfilled our requirements for a minimum ten-year follow-up.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 401 - 410
13 Jul 2021
Liu Z Wang H Wang S Gao J Niu L

Aims

Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Methods

The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 10, Issue 4 | Pages 277 - 284
1 Apr 2021
Funk GA Menuey EM Ensminger WP Kilway KV McIff TE

Aims

Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading.

Methods

For each cement (PMMA or SBB), three formulations were prepared (rifampin-added, vancomycin-added, and control) and made into pellets (6 mm × 12 mm) for testing. Antibiotic elution into phosphate-buffered saline was measured over 14 days. Compressive strength and modulus of all cement pellets were tested over 14 days.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 218 - 225
1 Mar 2021
Wiesli MG Kaiser J Gautier E Wick P Maniura-Weber K Rottmar M Wahl P

Aims

In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells.

Methods

Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.


Bone & Joint Research
Vol. 10, Issue 4 | Pages 237 - 249
1 Apr 2021
Chen X Chen W Aung ZM Han W Zhang Y Chai G

Aims

LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

Methods

The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 149 - 155
16 Feb 2021
Shiels SM Sgromolo NM Wenke JC

Aims

High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder.

Methods

Complex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 498 - 513
3 Aug 2021
Liu Z Lu C Shen P Chou S Shih C Chen J Tien YC

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Methods

Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 340 - 347
1 Jun 2021
Jenkinson MRJ Meek RMD Tate R MacMillan S Grant MH Currie S

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy.

Cite this article: Bone Joint Res 2021;10(6):340–347.


Bone & Joint Open
Vol. 2, Issue 5 | Pages 305 - 313
3 May 2021
Razii N Clutton JM Kakar R Morgan-Jones R

Aims

Periprosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA). Two-stage revision has traditionally been considered the gold standard of treatment for established infection, but increasing evidence is emerging in support of one-stage exchange for selected patients. The objective of this study was to determine the outcomes of single-stage revision TKA for PJI, with mid-term follow-up.

Methods

A total of 84 patients, with a mean age of 68 years (36 to 92), underwent single-stage revision TKA for confirmed PJI at a single institution between 2006 and 2016. In all, 37 patients (44%) were treated for an infected primary TKA, while the majority presented with infected revisions: 31 had undergone one previous revision (36.9%) and 16 had multiple prior revisions (19.1%). Contraindications to single-stage exchange included systemic sepsis, extensive bone or soft-tissue loss, extensor mechanism failure, or if primary wound closure was unlikely to be achievable. Patients were not excluded for culture-negative PJI or the presence of a sinus.


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 746 - 754
1 Apr 2021
Schnetzke M El Barbari J Schüler S Swartman B Keil H Vetter S Gruetzner PA Franke J

Aims

Complex joint fractures of the lower extremity are often accompanied by soft-tissue swelling and are associated with prolonged hospitalization and soft-tissue complications. The aim of the study was to evaluate the effect of vascular impulse technology (VIT) on soft-tissue conditioning in comparison with conventional elevation.

Methods

A total of 100 patients were included in this prospective, randomized, controlled monocentre study allocated to the three subgroups of dislocated ankle fracture (n = 40), pilon fracture (n = 20), and intra-articular calcaneal fracture (n = 40). Patients were randomized to the two study groups in a 1:1 ratio. The effectiveness of VIT (intervention) compared with elevation (control) was analyzed separately for the whole study population and for the three subgroups. The primary endpoint was the time from admission until operability (in days).


Bone & Joint Research
Vol. 9, Issue 11 | Pages 778 - 788
1 Nov 2020
Xu H Yang J Xie J Huang Z Huang Q Cao G Pei F

Aims

The efficacy and safety of intrawound vancomycin for preventing surgical site infection in primary hip and knee arthroplasty is uncertain.

Methods

A systematic review of the literature was conducted, indexed from inception to March 2020 in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases. All studies evaluating the efficacy and/or safety of intrawound vancomycin in patients who underwent primary hip and knee arthroplasty were included. Incidence of periprosthetic joint infection (PJI), superficial infection, aseptic wound complications, acute kidney injury, anaphylactic reaction, and ototoxicity were meta-analyzed. Results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). The quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool.


Bone & Joint Open
Vol. 2, Issue 2 | Pages 72 - 78
1 Feb 2021
Agni NR Costa ML Achten J O’Connor H Png ME Peckham N Dutton SJ Wallis S Milca S Reed M

Aims

Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture.

Methods

The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group.


Bone & Joint Research
Vol. 9, Issue 5 | Pages 211 - 218
1 May 2020
Hashimoto A Miyamoto H Kobatake T Nakashima T Shobuike T Ueno M Murakami T Noda I Sonohata M Mawatari M

Aims

Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation.

Methods

Pure titanium discs (Ti discs), Ti discs coated with HA (HA discs), and 3% Ag-HA discs developed using a thermal spraying were inoculated with MRSA suspensions containing a mean in vitro 4.3 (SD 0.8) x 106 or 43.0 (SD 8.4) x 105 colony-forming units (CFUs). Immediately after MRSA inoculation, sterile phosphate-buffered saline or VCM (20 µg/ml) was added, and the discs were incubated for 24 hours at 37°C. Viable cell counting, 3D confocal laser scanning microscopy with Airyscan, and scanning electron microscopy were then performed. HA discs and Ag HA discs were implanted subcutaneously in vivo in the dorsum of rats, and MRSA suspensions containing a mean in vivo 7.2 (SD 0.4) x 106  or 72.0 (SD 4.2) x 105  CFUs were inoculated on the discs. VCM was injected subcutaneously daily every 12 hours followed by viable cell counting.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 709 - 718
1 Oct 2020
Raina DB Liu Y Jacobson OLP Tanner KE Tägil M Lidgren L

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.


Bone & Joint Open
Vol. 1, Issue 9 | Pages 576 - 584
18 Sep 2020
Sun Z Liu W Li J Fan C

Post-traumatic elbow stiffness is a disabling condition that remains challenging for upper limb surgeons. Open elbow arthrolysis is commonly used for the treatment of stiff elbow when conservative therapy has failed. Multiple questions commonly arise from surgeons who deal with this disease. These include whether the patient has post-traumatic stiff elbow, how to evaluate the problem, when surgery is appropriate, how to perform an excellent arthrolysis, what the optimal postoperative rehabilitation is, and how to prevent or reduce the incidence of complications. Following these questions, this review provides an update and overview of post-traumatic elbow stiffness with respect to the diagnosis, preoperative evaluation, arthrolysis strategies, postoperative rehabilitation, and prevention of complications, aiming to provide a complete diagnosis and treatment path.

Cite this article: Bone Joint Open 2020;1-9:576–584.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 601 - 612
1 Sep 2020
Rajagopal K Ramesh S Walter NM Arora A Katti DS Madhuri V

Aims

Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Methods

Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 108 - 119
1 Mar 2020
Akhbari P Karamchandani U Jaggard MKJ Graça G Bhattacharya R Lindon JC Williams HRT Gupte CM

Aims

Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes.

Methods

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF.


Bone & Joint Research
Vol. 8, Issue 8 | Pages 387 - 396
1 Aug 2019
Alt V Rupp M Lemberger K Bechert T Konradt T Steinrücke P Schnettler R Söder S Ascherl R

Objectives

Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study.

Methods

A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 429 - 439
1 Jul 2020
Tahir M Chaudhry EA Zaffar Z Anwar K Mamoon MAH Ahmad M Jamali AR Mehboob G

Aims

We hypothesized that the wide-awake local anaesthesia with no tourniquet (WALANT) technique is cost-effective, easy to use, safe, and reproducible, with a low learning curve towards mastery, having a high patient satisfaction rate. Furthermore, WALANT would be a suitable alternative for the austere and developing nation environments where lack of funds and resources are a common issue.

Methods

This was a randomized control trial of 169 patients who required surgery for closed isolated distal radius fractures. The study was performed between March 2016 and April 2019 at a public sector level 1 trauma centre. General anaesthesia was used in 56 patients, Bier’s block in 58 patients, and WALANT in 55 patients. Data were collected on pre-, peri-, and postoperative parameters, clinical outcome, hospital costs, and patient satisfaction. One-way analysis of variance (ANOVA) was used with a p-value of 0.05 being significant.


Objectives

Irrigation is the cornerstone of treating skeletal infection by eliminating pathogens in wounds. A previous study shows that irrigation with normal saline (0.9%) and ethylenediaminetetraacetic acid (EDTA) could improve the removal of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) compared with normal saline (NS) alone. However, it is still unclear whether EDTA solution is effective against infection with drug-resistant bacteria.

Methods

We established three wound infection models (skin defect, bone-exposed, implant-exposed) by inoculating the wounds with a variety of representative drug-resistant bacteria including methicillin-resistant S. aureus (MRSA), extended spectrum beta-lactamase-producing E. coli (ESBL-EC), multidrug-resistant Pseudomonas aeruginosa (MRPA), vancomycin-resistant Enterococcus (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Enterobacter (MRE), and multidrug-resistant Proteus mirabilis (MRPM). Irrigation and debridement were repeated until the wound culture became negative. The operating times required to eliminate pathogens in wounds were compared through survival analysis.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 146 - 151
1 Mar 2020
Waldstein W Koller U Springer B Kolbitsch P Brodner W Windhager R Lass R

Aims

Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing.

Methods

The present study provides an update of a previously published prospective randomized controlled study, evaluating the serum cobalt levels of a consecutive cohort of 100 patients following THA with a MoM or a CoP articulation. A total of 31 patients were available for clinical and radiological follow-up examination. After exclusion of 11 patients because of other cobalt-containing implants, 20 patients (MoM (n = 11); CoP (n = 9)) with a mean age of 69 years (42 to 97) were analyzed. Serum cobalt levels were compared to serum cobalt levels five years out of surgery.


Bone & Joint Open
Vol. 1, Issue 4 | Pages 47 - 54
2 Apr 2020
Al-Mohrej OA Elshaer AK Al-Dakhil SS Sayed AI Aljohar S AlFattani AA Alhussainan TS

Introduction

Studies have addressed the issue of increasing prevalence of work-related musculoskeletal (MSK) pain among different occupations. However, contributing factors to MSK pain have not been fully investigated among orthopaedic surgeons. Thus, this study aimed to approximate the prevalence and predictors of MSK pain among Saudi orthopaedic surgeons working in Riyadh, Saudi Arabia.

Methods

A cross-sectional study using an electronic survey was conducted in Riyadh. The questionnaire was distributed through email among orthopaedic surgeons in Riyadh hospitals. Standardized Nordic questionnaires for the analysis of musculoskeletal symptoms were used. Descriptive measures for categorical and numerical variables were presented. Student’s t-test and Pearson’s χ2 test were used. The level of statistical significance was set at p ≤ 0.05.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

Methods

We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.


Bone & Joint Open
Vol. 2, Issue 1 | Pages 66 - 71
27 Jan 2020
Moriarty P Kayani B Wallace C Chang J Plastow R Haddad FS

Aims

Graft infection following anterior cruciate ligament reconstruction (ACLR) may lead to septic arthritis requiring multiple irrigation and debridement procedures, staged revision operations, and prolonged courses of antibiotics. To our knowledge, there are no previous studies reporting on how gentamicin pre-soaking of hamstring grafts influences infection rates following ACLR. We set out to examine this in our study accordingly.

Methods

This retrospective study included 2,000 patients (1,156 males and 844 females) who underwent primary ACLR with hamstring autografts between 2007 to 2017. This included 1,063 patients who received pre-soaked saline hamstring grafts for ACLR followed by 937 patients who received pre-soaked gentamicin hamstring grafts for ACLR. All operative procedures were completed by a single surgeon using a standardized surgical technique. Medical notes were reviewed and data relating to the following outcomes recorded: postoperative infection, clinical progress, causative organisms, management received, and outcomes.


Bone & Joint Research
Vol. 8, Issue 5 | Pages 199 - 206
1 May 2019
Romanò CL Tsuchiya H Morelli I Battaglia AG Drago L

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma.

Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.


Bone & Joint Research
Vol. 8, Issue 11 | Pages 526 - 534
1 Nov 2019
Yang C Wang J Yin Z Wang Q Zhang X Jiang Y Shen H

Objectives

The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics.

Methods

A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)).


Bone & Joint Research
Vol. 8, Issue 11 | Pages 526 - 534
1 Nov 2019
Yang C Wang J Yin Z Wang Q Zhang X Jiang Y Shen H

Objectives

The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics.

Methods

A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)).


Bone & Joint Research
Vol. 8, Issue 7 | Pages 333 - 341
1 Jul 2019
Grossner TL Haberkorn U Gotterbarm T

Objectives

Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that 99mTc-methylene diphosphonate (99mTc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA).

Methods

Within the present study, we evaluated whether this promising new method, using 99mTc-hydroxydiphosphonate (99mTc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with 99mTc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 255 - 265
1 Jun 2019
Hernigou J Schuind F

Objectives

The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular.

Methods

English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.


Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 157 - 165
1 Feb 2018
Sun Y Kiraly AJ Sun AR Cox M Mauerhan DR Hanley EN

Objectives

The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).

Methods

Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs.


Bone & Joint Research
Vol. 8, Issue 3 | Pages 146 - 155
1 Mar 2019
Langton DJ Natu S Harrington CF Bowsher JG Nargol AVF

Objectives

We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr.

Methods

For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 296 - 306
1 May 2017
Samara E Moriarty TF Decosterd LA Richards RG Gautier E Wahl P

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Methods

In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.


Bone & Joint Research
Vol. 8, Issue 1 | Pages 3 - 10
1 Jan 2019
Hernandez P Sager B Fa A Liang T Lozano C Khazzam M

Objectives

The purpose of this study was to examine the bactericidal efficacy of hydrogen peroxide (H2O2) on Cutibacterium acnes (C. acnes). We hypothesize that H2O2 reduces the bacterial burden of C. acnes.

Methods

The effect of H2O2 was assessed by testing bactericidal effect, time course analysis, growth inhibition, and minimum bactericidal concentration. To assess the bactericidal effect, bacteria were treated for 30 minutes with 0%, 1%, 3%, 4%, 6%, 8%, or 10% H2O2 in saline or water and compared with 3% topical H2O2 solution. For time course analysis, bacteria were treated with water or saline (controls), 3% H2O2 in water, 3% H2O2 in saline, or 3% topical solution for 5, 10, 15, 20, and 30 minutes. Results were analyzed with a two-way analysis of variance (ANOVA) (p < 0.05).


Bone & Joint Research
Vol. 7, Issue 10 | Pages 570 - 579
1 Oct 2018
Kallala R Harris WE Ibrahim M Dipane M McPherson E

Aims

Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature.

Methods

A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 447 - 456
1 Jul 2018
Morgenstern M Vallejo A McNally MA Moriarty TF Ferguson JY Nijs S Metsemakers W

Objectives

As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures.

Methods

A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 318 - 324
1 Apr 2018
González-Quevedo D Martínez-Medina I Campos A Campos F Carriel V

Objectives

Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries.

Methods

We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in animal models. The studies were screened for inclusion based on randomization, controls, and reported measurable outcomes. The RevMan software package was used for the meta-analysis.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 457 - 467
1 Jul 2018
Smith IDM Milto KM Doherty CJ Amyes SGB Simpson AHRW Hall AC

Objectives

Staphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability.

Methods

Bovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 370 - 378
1 Sep 2016
Munir S Oliver RA Zicat B Walter WL Walter WK Walsh WR

Objectives

This study aimed to characterise and qualitatively grade the severity of the corrosion particles released into the hip joint following taper corrosion.

Methods

The 26 cases examined were CoC/ABG Modular (n = 13) and ASR/SROM (n = 13). Blood serum metal ion levels were collected before and after revision surgery. The haematoxylin and eosin tissue sections were graded on the presence of fibrin exudates, necrosis, inflammatory cells and corrosion products. The corrosion products were identified based on visible observation and graded on abundance. Two independent observers blinded to the clinical patient findings scored all cases. Elemental analysis was performed on corrosion products within tissue sections. X-Ray diffraction was used to identify crystalline structures present in taper debris.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 179 - 186
1 Feb 2018
Wu T Zhang J Wang B Sun Y Liu Y Li G

Objectives

As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing.

Materials and Methods

Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 173 - 178
1 Feb 2018
Peng X Wu X Zhang J Zhang G Li G Pan X

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment.

Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 105 - 110
1 Jan 2018
Abar O Dharmar S Tang SY

Objectives

Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality.

Methods

An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 427 - 435
1 Sep 2016
Stravinskas M Horstmann P Ferguson J Hettwer W Nilsson M Tarasevicius S Petersen MM McNally MA Lidgren L

Objectives

Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.

The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.

DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.

Materials and Methods

We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 162 - 168
1 May 2016
Athanasou NA

Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles.

Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–168. DOI: 10.1302/2046-3758.55.BJR-2016-0086.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 46 - 57
1 Jan 2018
Zhou J Zhou XG Wang JW Zhou H Dong J

Objective

In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits.

Methods

The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects.


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1420 - 1430
1 Nov 2017
Azboy I Barrack R Thomas AM Haddad FS Parvizi J

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences.

Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a ‘milder’ agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents.

The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use.

There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE.

Cite this article: Bone Joint J 2017;99-B:1420–30.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 500 - 511
1 Oct 2016
Raina DB Gupta A Petersen MM Hettwer W McNally M Tägil M Zheng M Kumar A Lidgren L

Objectives

We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.

Materials and Methods

We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 345 - 350
1 May 2017
Di Laura A Hothi H Henckel J Swiatkowska I Liow MHL Kwon Y Skinner JA Hart AJ

Objectives

The use of ceramic femoral heads in total hip arthroplasty (THA) has increased due to their proven low bearing wear characteristics. Ceramic femoral heads are also thought to reduce wear and corrosion at the head-stem junction with titanium (Ti) stems when compared with metal heads. We sought to evaluate taper damage of ceramic compared with metal heads when paired with cobalt chromium (CoCr) alloy stems in a single stem design.

Methods

This retrieval study involved 48 total hip arthroplasties (THAs) with CoCr V40 trunnions paired with either CoCr (n = 21) or ceramic (n = 27) heads. The taper junction of all hips was evaluated for fretting/corrosion damage and volumetric material loss using a roundness-measuring machine. We used linear regression analysis to investigate taper damage differences after adjusting for potential confounding variables.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 307 - 314
1 May 2017
Rendon JS Swinton M Bernthal N Boffano M Damron T Evaniew N Ferguson P Galli Serra M Hettwer W McKay P Miller B Nystrom L Parizzia W Schneider P Spiguel A Vélez R Weiss K Zumárraga JP Ghert M

Objectives

As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration.

Methods

All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation.


Aims

The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft-tissue complications associated with socket prostheses and by improving sensory feedback and function. It relies on the formation of a seal between the soft tissues and the implant and currently has a flange with drilled holes to promote dermal attachment. Despite this, infection remains a significant risk. This study explored alternative strategies to enhance soft-tissue integration.

Materials and Methods

The effect of ITAP pins with a fully porous titanium alloy flange with interconnected pores on soft-tissue integration was investigated. The flanges were coated with fibronectin-functionalised hydroxyapatite and silver coatings, which have been shown to have an antibacterial effect, while also promoting viable fibroblast growth in vitro. The ITAP pins were implanted along the length of ovine tibias, and histological assessment was undertaken four weeks post-operatively.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 144 - 153
1 Mar 2017
Kharwadkar N Mayne B Lawrence JE Khanduja V

Objectives

Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.

Methods

We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use.


Objective

To study the effect of hyaluronic acid (HA) on local anaesthetic chondrotoxicity in vitro.

Methods

Chondrocytes were harvested from bovine femoral condyle cartilage and isolated using collagenase-containing media. At 24 hours after seeding 15 000 cells per well onto a 96-well plate, chondrocytes were treated with media (DMEM/F12 + ITS), PBS, 1:1 lidocaine (2%):PBS, 1:1 bupivacaine (0.5%):PBS, 1:1 lidocaine (2%):HA, 1:1 bupivacaine (0. 5%):HA, or 1:1 HA:PBS for one hour. Following treatment, groups had conditions removed and 24-hour incubation. Cell viability was assessed using PrestoBlue and confirmed visually using fluorescence microscopy.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 215 - 217
1 Jun 2016
Pijls BG Nelissen RGHH


Bone & Joint Research
Vol. 5, Issue 10 | Pages 512 - 519
1 Oct 2016
Mills L Tsang J Hopper G Keenan G Simpson AHRW

Objectives

A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion.

Methods

Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host. Prospective and retrospective data of 100 consecutive patients who had undergone surgery for long bone fracture nonunion were analysed.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 560 - 568
1 Nov 2016
Peeters M Huang CL Vonk LA Lu ZF Bank RA Helder MN Doulabi BZ

Objectives

Studies which consider the molecular mechanisms of degeneration and regeneration of cartilaginous tissues are seriously hampered by problematic ribonucleic acid (RNA) isolations due to low cell density and the dense, proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co-purify with RNA, they can absorb the full spectrum of UV light and they are potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of the present study is to compare and optimise different homogenisation methods and RNA isolation kits for an array of cartilaginous tissues.

Materials and Methods

Tissue samples such as the nucleus pulposus (NP), annulus fibrosus (AF), articular cartilage (AC) and meniscus, were collected from goats and homogenised by either the MagNA Lyser or Freezer Mill. RNA of duplicate samples was subsequently isolated by either TRIzol (benchmark), or the RNeasy Lipid Tissue, RNeasy Fibrous Tissue, or Aurum Total RNA Fatty and Fibrous Tissue kits. RNA yield, purity, and integrity were determined and gene expression levels of type II collagen and aggrecan were measured by real-time PCR.