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Bone & Joint Research
Vol. 5, Issue 6 | Pages 206 - 214
1 Jun 2016
Malak TT Broomfield JAJ Palmer AJR Hopewell S Carr A Brown C Prieto-Alhambra D Glyn-Jones S

Objectives. High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long-term outcome in patients undergoing primary total hip arthroplasty (THA). Methods. We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015. Results. Our search strategy identified 1082 studies of which 115 studies were included for full article review. Following review, 17 articles were found that investigated surrogate markers of long-term outcome. These included one systematic review, one randomised control trial (RCT), one case control study and 13 case series. Validated surrogate markers included Radiostereometric Analysis (RSA) and Einzel-Bild-Röntgen-Analyse (EBRA), each measuring implant migration and wear. We identified five RSA studies (one systematic review and four case series) and four EBRA studies (one RCT and three case series). Patient Reported Outcome Measures (PROMs) at six months have been investigated but have not been validated against long-term outcomes. Conclusions. This systematic review identified two validated surrogate markers of long-term primary THA outcome: RSA and EBRA, each measuring implant migration and wear. We recommend the consideration of RSA in the pre-market testing of new implants. EBRA can be used to investigate acetabular wear but not femoral migration. Further studies are needed to validate the use of PROMs for post-market surveillance. Cite this article: T. T. Malak, J. A. J. Broomfield, A. J. R. Palmer, S. Hopewell, A. Carr, C. Brown, D. Prieto-Alhambra, S. Glyn-Jones. Surrogate markers of long-term outcome in primary total hip arthroplasty: A systematic review. Bone Joint Res 2016;5:206–214. DOI: 10.1302/2046-3758.56.2000568


Bone & Joint Research
Vol. 10, Issue 5 | Pages 321 - 327
3 May 2021
Walter N Rupp M Hierl K Pfeifer C Kerschbaum M Hinterberger T Alt V

Aims. We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results. With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion. Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients. Cite this article: Bone Joint Res 2021;10(5):321–327


Bone & Joint Research
Vol. 3, Issue 10 | Pages 297 - 304
1 Oct 2014
Fitch DA Sedacki K Yang Y

Objectives. This systematic review and meta-analysis was conducted to determine the mid- to long-term clinical outcomes for a medial-pivot total knee replacement (TKR) system. The objectives were to synthesise available survivorship, Knee Society Scores (KSS), and reasons for revision for this system. Methods. A systematic search was conducted of two online databases to identify sources of survivorship, KSS, and reasons for revision. Survivorship results were compared with values in the National Joint Registry of England, Wales, and Northern Ireland (NJR). Results. A total of eight studies that included data for 1146 TKRs performed in six countries satisfied the inclusion/exclusion criteria. Pooled component survivorship estimates were 99.2% (95% CI, 97.7 to 99.7) and 97.6% (95% CI, 95.8 to 98.6) at five and eight years, respectively. Survivorship was similar or better when compared with rates reported for all cemented TKRs combined in the NJR and was significantly better than some insert types at mid-term intervals. The weighted mean post-operative KSS was 87.9 (73.2 to 94.2), in the excellent range. Similar cumulative revision rates and KSS were reported at centres in the United States, Europe, and Asia. Conclusions. The subject system was associated with survivorship and KSS similar or better than that reported for other TKR systems. Cite this article: Bone Joint Res 2014;3:297–304


Bone & Joint Research
Vol. 3, Issue 1 | Pages 1 - 6
1 Jan 2014
Yamada K Mihara H Fujii H Hachiya M

Objectives. There are several reports clarifying successful results following open reduction using Ludloff’s medial approach for congenital (CDH) or developmental dislocation of the hip (DDH). This study aimed to reveal the long-term post-operative course until the period of hip-joint maturity after the conventional surgical treatments. Methods. A long-term follow-up beyond the age of hip-joint maturity was performed for 115 hips in 103 patients who underwent open reduction using Ludloff’s medial approach in our hospital. The mean age at surgery was 8.5 months (2 to 26) and the mean follow-up was 20.3 years (15 to 28). The radiological condition at full growth of the hip joint was evaluated by Severin’s classification. Results. All 115 hips successfully attained reduction after surgery; however, 74 hips (64.3%) required corrective surgery at a mean age of 2.6 years (one to six). According to Severin’s classification, 69 hips (60.0%) were classified as group I or II, which were considered to represent acceptable results. A total of 39 hips (33.9%) were group III and the remaining seven hips (6.1%) group IV. As to re-operation, 20 of 21 patients who underwent surgical reduction after 12 months of age required additional corrective surgeries during the growth period as the hip joint tended to subluxate gradually. Conclusion. Open reduction using Ludloff’s medial approach accomplished successful joint reduction for persistent CDH or DDH, but this surgical treatment was only appropriate before the ambulating stage. Cite this article: Bone Joint Res 2014;3:1–6


Bone & Joint Research
Vol. 6, Issue 10 | Pages 602 - 609
1 Oct 2017
Jin A Cobb J Hansen U Bhattacharya R Reinhard C Vo N Atwood R Li J Karunaratne A Wiles C Abel R

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1


Bone & Joint Research
Vol. 8, Issue 11 | Pages 535 - 543
1 Nov 2019
Mohammad HR Campi S Kennedy JA Judge A Murray DW Mellon SJ

Objectives

The aim of this study was to determine the polyethylene wear rate of Phase 3 Oxford Unicompartmental Knee Replacement bearings and to investigate the effects of resin type and manufacturing process.

Methods

A total of 63 patients with at least ten years’ follow-up with three bearing types (1900 resin machined, 1050 resin machined, and 1050 resin moulded) were recruited. Patients underwent full weight-bearing model-based radiostereometric analysis to determine the bearing thickness. The linear wear rate was estimated from the change in thickness divided by the duration of implantation.


Bone & Joint Research
Vol. 2, Issue 7 | Pages 132 - 139
1 Jul 2013
Ketola S Lehtinen J Rousi T Nissinen M Huhtala H Konttinen YT Arnala I

Objectives

To report the five-year results of a randomised controlled trial examining the effectiveness of arthroscopic acromioplasty in the treatment of stage II shoulder impingement syndrome.

Methods

A total of 140 patients were randomly divided into two groups: 1) supervised exercise programme (n = 70, exercise group); and 2) arthroscopic acromioplasty followed by a similar exercise programme (n = 70, combined treatment group).


Bone & Joint Research
Vol. 11, Issue 12 | Pages 843 - 853
1 Dec 2022
Cai Y Huang C Chen X Chen Y Huang Z Zhang C Zhang W Fang X

Aims. This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). Methods. A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). Results. SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. Conclusion. Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI. Cite this article: Bone Joint Res 2022;11(12):843–853


Bone & Joint Research
Vol. 11, Issue 6 | Pages 342 - 345
1 Jun 2022
Hall AJ Clement ND MacLullich AMJ Simpson AHRW White TO Duckworth AD

Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies. Cite this article: Bone Joint Res 2022;11(6):342–345


Bone & Joint Research
Vol. 10, Issue 7 | Pages 425 - 436
16 Jul 2021
Frommer A Roedl R Gosheger G Hasselmann J Fuest C Toporowski G Laufer A Tretow H Schulze M Vogt B

Aims. This study aims to enhance understanding of clinical and radiological consequences and involved mechanisms that led to corrosion of the Precice Stryde (Stryde) intramedullary lengthening nail in the post market surveillance era of the device. Between 2018 and 2021 more than 2,000 Stryde nails have been implanted worldwide. However, the outcome of treatment with the Stryde system is insufficiently reported. Methods. This is a retrospective single-centre study analyzing outcome of 57 consecutive lengthening procedures performed with the Stryde nail at the authors’ institution from February 2019 until November 2020. Macro- and microscopic metallographic analysis of four retrieved nails was conducted. To investigate observed corrosion at telescoping junction, scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDX) were performed. Results. Adjacent to the nail’s telescoping junction, osteolytic changes were observed in bi-planar radiographs of 20/57 segments (35%) after a mean of 9.5 months (95% confidence interval 7.2 to 11.9) after surgery. A total of 8/20 patients with osseous alterations (40%) reported rest and ambulation pain of the lengthened segment during consolidation. So far, 24 Stryde nails were retrieved and in 20 (83%) macroscopic corrosion was observed at the nail’s telescoping junction. Before implant removal 11/20 radiographs (55%) of lengthened segments with these 20 nails revealed osteolysis. Implant retrieval analysis by means of SEM showed pitting and crevice corrosion. EDX detected chromium as the main metallic element of corrosion. Conclusion. Patients are exposed to the risk of implant-related osteolysis of unclear short- and long-term clinical consequences. The authors advocate in favour of an early implant removal after osseous consolidation. Cite this article: Bone Joint Res 2021;10(7):425–436


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


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 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. 12, Issue 9 | Pages 559 - 570
14 Sep 2023
Wang Y Li G Ji B Xu B Zhang X Maimaitiyiming A Cao L

Aims

To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA).

Methods

The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 306 - 314
19 Jun 2024
Wu B Su J Zhang Z Zeng J Fang X Li W Zhang W Huang Z

Aims

To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).

Methods

A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001).


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. 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.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 193 - 200
23 Apr 2024
Reynolds A Doyle R Boughton O Cobb J Muirhead-Allwood S Jeffers J

Aims

Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies.

Methods

Posterior approach THAs were carried out on three cadavers by an expert orthopaedic surgeon. An instrumented mallet and introducer were used to insert cementless acetabular cups. The motion of the mallet, relative to the introducer, was analyzed for a total of 110 strikes split into low-, medium-, and high-effort strikes. Three parameters were extracted from these data: strike vector, strike offset, and mallet face alignment.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 611 - 621
24 Oct 2024
Wan Q Han Q Liu Y Chen H Zhang A Zhao X Wang J

Aims

This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture.

Methods

Ten different sagittal placements of the femoral component, ranging from -5 mm (causing anterior notch) to +4 mm (causing anterior gap), were analyzed using finite element analysis. Both gait and squat loading conditions were simulated, and Von Mises stress and interface micromotion were evaluated to assess fracture and loosening risk.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 362 - 371
1 Jun 2023
Xu D Ding C Cheng T Yang C Zhang X

Aims

The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD.

Methods

A comprehensive literature search was conducted to identify eligible studies reporting postoperative outcomes in IBD patients undergoing joint arthroplasty. The primary outcomes included postoperative complications, while the secondary outcomes included unplanned readmission, length of stay (LOS), joint reoperation/implant revision, and cost of care. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model when heterogeneity was substantial.


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. 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. 13, Issue 9 | Pages 507 - 512
18 Sep 2024
Farrow L Meek D Leontidis G Campbell M Harrison E Anderson L

Despite the vast quantities of published artificial intelligence (AI) algorithms that target trauma and orthopaedic applications, very few progress to inform clinical practice. One key reason for this is the lack of a clear pathway from development to deployment. In order to assist with this process, we have developed the Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework – a five-stage approach to the clinical practice adoption of AI in the setting of trauma and orthopaedics, based on the IDEAL principles (https://www.ideal-collaboration.net/). Adherence to the framework would provide a robust evidence-based mechanism for developing trust in AI applications, where the underlying algorithms are unlikely to be fully understood by clinical teams.

Cite this article: Bone Joint Res 2024;13(9):507–512.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 315 - 320
1 Jul 2024
Choi YH Kwon TH Choi JH Han HS Lee KM

Aims

Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation.

Methods

This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 497 - 503
16 Aug 2023
Lee J Koh Y Kim PS Park J Kang K

Aims

Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

Methods

The mechanical behaviour of the cartilage surrounding a metal implant was evaluated using finite element analysis. We modelled focal knee arthroplasty with placement flush, 0.5 mm deep, or protruding 0.5 mm with regard to the level of the surrounding cartilage. We compared contact stress and pressure for bone, implant, and cartilage under static loading conditions.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 212 - 218
9 Mar 2023
Buchalter DB Kirby DJ Anil U Konda SR Leucht P

Aims

Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability.

Methods

A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 72 - 79
18 Jan 2023
Welling MM Warbroek K Khurshid C van Oosterom MN Rietbergen DDD de Boer MGJ Nelissen RGHH van Leeuwen FWB Pijls BG Buckle T

Aims

Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods.

Methods

99mTc-UBI29-41-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria.


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 Research
Vol. 12, Issue 10 | Pages 636 - 643
10 Oct 2023
Hamilton V Sheikh S Szczepanska A Maskell N Hamilton F Reid JP Bzdek BR Murray JRD

Aims

Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians’ health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations.

Methods

The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 353 - 361
10 Jul 2024
Gardete-Hartmann S Mitterer JA Sebastian S Frank BJH Simon S Huber S Löw M Sommer I Prinz M Halabi M Hofstaetter JG

Aims

This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool.

Methods

Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 19 - 27
5 Jan 2024
Baertl S Rupp M Kerschbaum M Morgenstern M Baumann F Pfeifer C Worlicek M Popp D Amanatullah DF Alt V

Aims

This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated.

Methods

A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss’ kappa and Cohen’s kappa were calculated for interobserver and intraobserver reliability, respectively.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 245 - 255
3 Apr 2023
Ryu S So J Ha Y Kuh S Chin D Kim K Cho Y Kim K

Aims

To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory.

Methods

Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 91 - 100
1 Mar 2024
Yamamoto Y Fukui T Sawauchi K Yoshikawa R Takase K Kumabe Y Maruo A Niikura T Kuroda R Oe K

Aims

Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells.

Methods

Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies.


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 (CaSO4) 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 CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 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).


Bone & Joint Research
Vol. 13, Issue 5 | Pages 237 - 246
17 May 2024
Cheng B Wu C Wei W Niu H Wen Y Li C Chen P Chang H Yang Z Zhang F

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Methods

Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.


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 5 | Pages 321 - 330
9 May 2023
Lenguerrand E Whitehouse MR Beswick AD Kunutsor SK Webb JCJ Mehendale S Porter M Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


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.


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.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.


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 5 | Pages 226 - 236
9 May 2024
Jürgens-Lahnstein JH Petersen ET Rytter S Madsen F Søballe K Stilling M

Aims

Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear.

Methods

A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay.


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 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims

Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing.

Methods

A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.


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 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 546 - 558
12 Sep 2023
Shen J Wei Z Wang S Wang X Lin W Liu L Wang G

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Methods

A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data.


Aims

To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).

Methods

Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.


Aims

This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Methods

In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 715 - 722
10 Oct 2022
Matsuyama Y Nakamura T Yoshida K Hagi T Iino T Asanuma K Sudo A

Aims

Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases.

Methods

We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 739 - 750
4 Oct 2022
Shu L Abe N Li S Sugita N

Aims

To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle.

Methods

In this controlled laboratory study, we developed an original multiscale subject-specific finite element musculoskeletal framework model and integrated it with the tibiofemoral and patellofemoral joints with high-fidelity joint motion representations, to investigate the effects of 2.5° increases in PTS angles on joint dynamics and contact mechanics during the gait cycle.


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.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 426 - 438
20 Jul 2022
Luo P Wang P Xu J Hou W Xu P Xu K Liu L

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 629 - 638
1 Sep 2022
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Aims

Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms.

Methods

Mature biofilms of S. aureus (ATCC 29213) were grown on titanium alloy (Ti6Al4V) coupons for seven days and were subjected to the following treatments or their combinations: antibiotics, mechanical cleaning, or heat shock by induction heating of 60°C for one minute. Experiments were repeated at least five times.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 669 - 678
1 Sep 2022
Clement RGE Hall AC Wong SJ Howie SEM Simpson AHRW

Aims

Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.

Methods

Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 514 - 517
10 Aug 2022
Little CB Zaki S Blaker CL Clarke EC

Cite this article: Bone Joint Res 2022;11(8):514–517.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 594 - 607
17 Aug 2022
Zhou Y Li J Xu F Ji E Wang C Pan Z

Aims

Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA.

Methods

Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 561 - 574
10 Aug 2022
Schulze-Tanzil GG Delgado Cáceres M Stange R Wildemann B Docheva D

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 528 - 540
1 Aug 2022
Dong W Postlethwaite BC Wheller PA Brand D Jiao Y Li W Myers LK Gu W

Aims

This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Methods

A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay.


Bone & Joint Research
Vol. 11, Issue 5 | Pages 260 - 269
3 May 2022
Staats K Sosa BR Kuyl E Niu Y Suhardi V Turajane K Windhager R Greenblatt MB Ivashkiv L Bostrom MPG Yang X

Aims

To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants.

Methods

3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 386 - 397
22 Jun 2022
Zhu D Fang H Yu H Liu P Yang Q Luo P Zhang C Gao Y Chen Y

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Methods

MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 210 - 213
1 Apr 2022
Fontalis A Haddad FS


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. Results. Six broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone mineralisation and altered collagen formation. The key themes in fracture management are: medical therapy and surgical therapy. In addition, primary prevention strategies for AFFs are discussed. Conclusions. This article presents current knowledge about the relationship between bisphosphonates and the development of AFFs, and highlights key areas for future research. In particular, studies aimed at identifying at-risk subpopulations and organising surveillance for those on long-term therapy will be crucial in both increasing our understanding of the condition, and improving population outcomes. Cite this article: N. Kharwadkar, B. Mayne, J. E. Lawrence, V. Khanduja. Bisphosphonates and atypical subtrochanteric fractures of the femur. Bone Joint Res 2017;6:144–153. DOI: 10.1302/2046-3758.63.BJR-2016-0125.R1


Bone & Joint Research
Vol. 11, Issue 1 | Pages 23 - 25
17 Jan 2022
Matar HE Platt SR Bloch BV Board TN Porter ML Cameron HU James PJ


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. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1


Aims

There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA.

Methods

We searched PubMed, EMBASE, and the Cochrane Library for cohort studies that assessed the effect of preoperative injection of drugs into the joint cavity on the infection rate after TKA. The outcomes analyzed included the total infection rate, as well as those for different preoperative injection time periods and different drugs.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 49 - 60
1 Feb 2022
Li J Wong RMY Chung YL Leung SSY Chow SK Ip M Cheung W

Aims

With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

Methods

A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 104 colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed.


Aims

There are concerns regarding nail/medullary canal mismatch and initial stability after cephalomedullary nailing in unstable pertrochanteric fractures. This study aimed to investigate the effect of an additional anteroposterior blocking screw on fixation stability in unstable pertrochanteric fracture models with a nail/medullary canal mismatch after short cephalomedullary nail (CMN) fixation.

Methods

Eight finite element models (FEMs), comprising four different femoral diameters, with and without blocking screws, were constructed, and unstable intertrochanteric fractures fixed with short CMNs were reproduced in all FEMs. Micromotions of distal shaft fragment related to proximal fragment, and stress concentrations at the nail construct were measured.


Bone & Joint Research
Vol. 11, Issue 1 | Pages 10 - 11
11 Jan 2022
Snowden GT Clement ND Zhang S Xue Q Simpson AHRW


Bone & Joint Research
Vol. 11, Issue 3 | Pages 143 - 151
1 Mar 2022
Goetz J Keyssner V Hanses F Greimel F Leiß F Schwarz T Springorum H Grifka J Schaumburger J

Aims

Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA.

Methods

For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 82 - 90
7 Feb 2022
Eckert JA Bitsch RG Sonntag R Reiner T Schwarze M Jaeger S

Aims

The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two variants: single and twin peg OUKA. The purpose of this study was to assess the stability of both variants in a worst-case scenario of bone defects and suboptimal cementation.

Methods

Single and twin pegs were implanted randomly allocated in 12 pairs of human fresh-frozen femora. We generated 5° bone defects at the posterior condyle. Relative movement was simulated using a servohydraulic pulser, and analyzed at 70°/115° knee flexion. Relative movement was surveyed at seven points of measurement on implant and bone, using an optic system.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 91 - 101
1 Feb 2022
Munford MJ Stoddart JC Liddle AD Cobb JP Jeffers JRT

Aims

Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia.

Methods

In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 122 - 129
1 Apr 2016
Small SR Rogge RD Malinzak RA Reyes EM Cook PL Farley KA Ritter MA

Objectives. Initial stability of tibial trays is crucial for long-term success of total knee arthroplasty (TKA) in both primary and revision settings. Rotating platform (RP) designs reduce torque transfer at the tibiofemoral interface. We asked if this reduced torque transfer in RP designs resulted in subsequently reduced micromotion at the cemented fixation interface between the prosthesis component and the adjacent bone. Methods. Composite tibias were implanted with fixed and RP primary and revision tibial trays and biomechanically tested under up to 2.5 kN of axial compression and 10° of external femoral component rotation. Relative micromotion between the implanted tibial tray and the neighbouring bone was quantified using high-precision digital image correlation techniques. Results. Rotational malalignment between femoral and tibial components generated 40% less overall tibial tray micromotion in RP designs than in standard fixed bearing tibial trays. RP trays reduced micromotion by up to 172 µm in axial compression and 84 µm in rotational malalignment models. Conclusions. Reduced torque transfer at the tibiofemoral interface in RP tibial trays reduces relative component micromotion and may aid long-term stability in cases of revision TKA or poor bone quality. Cite this article: Mr S. R. Small. Micromotion at the tibial plateau in primary and revision total knee arthroplasty: fixed versus rotating platform designs. Bone Joint Res 2016;5:122–129. DOI: 10.1302/2046-3758.54.2000481


Bone & Joint Research
Vol. 11, Issue 1 | Pages 12 - 22
13 Jan 2022
Zhang F Rao S Baranova A

Aims

Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.

Methods

Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 790 - 796
1 Dec 2021
Fang X Wang Q Yang X Zhang F Huang C Huang Z Shen H Zhang W

Aims

To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI).

Methods

This study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 693 - 703
1 Oct 2021
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Methods

In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB).


Bone & Joint Research
Vol. 10, Issue 11 | Pages 723 - 733
1 Nov 2021
Garner AJ Dandridge OW Amis AA Cobb JP van Arkel RJ

Aims

Bi-unicondylar arthroplasty (Bi-UKA) is a bone and anterior cruciate ligament (ACL)-preserving alternative to total knee arthroplasty (TKA) when the patellofemoral joint is preserved. The aim of this study is to investigate the clinical outcomes and biomechanics of Bi-UKA.

Methods

Bi-UKA subjects (n = 22) were measured on an instrumented treadmill, using standard gait metrics, at top walking speeds. Age-, sex-, and BMI-matched healthy (n = 24) and primary TKA (n = 22) subjects formed control groups. TKA subjects with preoperative patellofemoral or tricompartmental arthritis or ACL dysfunction were excluded. The Oxford Knee Score (OKS) and EuroQol five-dimension questionnaire (EQ-5D) were compared. Bi-UKA, then TKA, were performed on eight fresh frozen cadaveric knees, to investigate knee extensor efficiency under controlled laboratory conditions, using a repeated measures study design.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 690 - 692
1 Oct 2021
Hoellwarth JS Tetsworth K Akhtar MA Al Muderis M


Bone & Joint Research
Vol. 10, Issue 10 | Pages 650 - 658
1 Oct 2021
Sanghani-Kerai A Black C Cheng SO Collins L Schneider N Blunn G Watson F Fitzpatrick N

Aims

This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.

Methods

With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 263 - 273
1 Apr 2018
Ferreira E Porter RM

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006


Bone & Joint Research
Vol. 6, Issue 11 | Pages 623 - 630
1 Nov 2017
Suh D Kang K Son J Kwon O Baek C Koh Y

Objectives. Malalignment of the tibial component could influence the long-term survival of a total knee arthroplasty (TKA). The object of this study was to investigate the biomechanical effect of varus and valgus malalignment on the tibial component under stance-phase gait cycle loading conditions. Methods. Validated finite element models for varus and valgus malalignment by 3° and 5° were developed to evaluate the effect of malalignment on the tibial component in TKA. Maximum contact stress and contact area on a polyethylene insert, maximum contact stress on patellar button and the collateral ligament force were investigated. Results. There was greater total contact stress in the varus alignment than in the valgus, with more marked difference on the medial side. An increase in ligament force was clearly demonstrated, especially in the valgus alignment and force exerted on the medial collateral ligament also increased. Conclusion. These results highlight the importance of accurate surgical reconstruction of the coronal tibial alignment of the knee joint. Varus and valgus alignments will influence wear and ligament stability, respectively in TKA. Cite this article: D-S. Suh, K-T. Kang, J. Son, O-R. Kwon, C. Baek, Y-G. Koh. Computational study on the effect of malalignment of the tibial component on the biomechanics of total knee arthroplasty: A Finite Element Analysis. Bone Joint Res 2017;6:623–630. DOI: 10.1302/2046-3758.611.BJR-2016-0088.R2


Bone & Joint Research
Vol. 10, Issue 8 | Pages 474 - 487
2 Aug 2021
Duan M Wang Q Liu Y Xie J

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 205 - 212
1 Mar 2018
Lin Y Hall AC Simpson AHRW

Objectives. The purpose of this study was to create a novel ex vivo organ culture model for evaluating the effects of static and dynamic load on cartilage. Methods. The metatarsophalangeal joints of 12 fresh cadaveric bovine feet were skinned and dissected aseptically, and cultured for up to four weeks. Dynamic movement was applied using a custom-made machine on six joints, with the others cultured under static conditions. Chondrocyte viability and matrix glycosaminoglycan (GAG) content were evaluated by the cell viability probes, 5-chloromethylfluorescein diacetate (CMFDA) and propidium iodide (PI), and dimethylmethylene blue (DMMB) assay, respectively. Results. Chondrocyte viability in the static model decreased significantly from 89.9% (. sd. 2.5%) (Day 0) to 66.5% (. sd. 13.1%) (Day 28), 94.7% (. sd. 1.1%) to 80. 9% (. sd. 5.8%) and 80.1% (. sd. 3.0%) to 46.9% (. sd. 8.5%) in the superficial quarter, central half and deep quarter of cartilage, respectively (p < 0.001 in each zone; one-way analysis of variance). The GAG content decreased significantly from 6.01 μg/mg (. sd. 0.06) (Day 0) to 4.71 μg/mg (. sd. 0.06) (Day 28) (p < 0.001; one-way analysis of variance). However, with dynamic movement, chondrocyte viability and GAG content were maintained at the Day 0 level over the four-week period without a significant change (chondrocyte viability: 92.0% (. sd. 4.0%) (Day 0) to 89.9% (. sd. 0.2%) (Day 28), 93.1% (. sd. 1.5%) to 93.8% (. sd. 0.9%) and 85.6% (. sd. 0.8%) to 84.0% (. sd. 2.9%) in the three corresponding zones; GAG content: 6.18 μg/mg (. sd. 0.15) (Day 0) to 6.06 μg/mg (. sd. 0.09) (Day 28)). Conclusion. Dynamic joint movement maintained chondrocyte viability and cartilage GAG content. This long-term whole joint culture model could be of value in providing a more natural and controlled platform for investigating the influence of joint movement on articular cartilage, and for evaluating novel therapies for cartilage repair. Cite this article: Y-C. Lin, A. C. Hall, A. H. R. W. Simpson. A novel organ culture model of a joint for the evaluation of static and dynamic load on articular cartilage. Bone Joint Res 2018;7:205–212. DOI: 10.1302/2046-3758.73.BJR-2017-0320


Bone & Joint Research
Vol. 10, Issue 8 | Pages 548 - 557
25 Aug 2021
Tao Z Zhou Y Zeng B Yang X Su M

Aims

MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms.

Methods

Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 414 - 422
1 Jul 2017
Phetfong J Tawonsawatruk T Seenprachawong K Srisarin A Isarankura-Na-Ayudhya C Supokawej A

Objectives. Adipose-derived mesenchymal stem cells (ADMSCs) are a promising strategy for orthopaedic applications, particularly in bone repair. Ex vivo expansion of ADMSCs is required to obtain sufficient cell numbers. Xenogenic supplements should be avoided in order to minimise the risk of infections and immunological reactions. Human platelet lysate and human plasma may be an excellent material source for ADMSC expansion. In the present study, use of blood products after their recommended transfusion date to prepare human platelet lysate (HPL) and human plasma (Hplasma) was evaluated for in vitro culture expansion and osteogenesis of ADMSCs. Methods. Human ADMSCs were cultured in medium supplemented with HPL, Hplasma and a combination of HPL and Hplasma (HPL+Hplasma). Characteristics of these ADMSCs, including osteogenesis, were evaluated in comparison with those cultured in fetal bovine serum (FBS). Results. HPL and HPL+Hplasma had a significantly greater growth-promoting effect than FBS, while Hplasma exhibited a similar growth-promoting effect to that of FBS. ADMSCs cultured in HPL and/or Hplasma generated more colony-forming unit fibroblasts (CFU-F) than those cultured in FBS. After long-term culture, ADMSCs cultured in HPL and/or Hplasma showed reduced cellular senescence, retained typical cell phenotypes, and retained differentiation capacities into osteogenic and adipogenic lineages. Conclusion. HPL and Hplasma prepared from blood products after their recommended transfusion date can be used as an alternative and effective source for large-scale ex vivo expansion of ADMSCs. Cite this article: J. Phetfong, T. Tawonsawatruk, K. Seenprachawong, A. Srisarin, C. Isarankura-Na-Ayudhya, A. Supokawej. Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture. Bone Joint Res 2017;6:414–422. DOI: 10.1302/2046-3758.67.BJR-2016-0342.R1


Bone & Joint Research
Vol. 10, Issue 8 | Pages 488 - 497
10 Aug 2021
Cleemann R Sorensen M West A Soballe K Bechtold JE Baas J

Aims

We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants.

Methods

An established allografted revision protocol was implemented bilaterally into the stifle joints of 24 canines. At revision surgery, each animal received one BMP-2 (5 µg) functionalized implant, and one raw implant. One group (12 animals) received bone graft impregnated with zoledronate (0.005 mg/ml) before impaction. The other group (12 animals) received untreated bone graft and systemic zoledronate (0.1 mg/kg) ten and 20 days after revision surgery. Animals were observed for an additional four weeks before euthanasia.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 445 - 458
7 Jul 2021
Zhu S Zhang X Chen X Wang Y Li S Qian W

Aims

The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone.

Methods

We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 437 - 444
27 Jul 2021
Yan F Feng J Yang L Shi C

Aims

The aim of our study is to investigate the effect induced by alternated mechanical loading on Notch-1 in mandibular condylar cartilage (MCC) of growing rabbits.

Methods

A total of 64 ten-day-old rabbits were randomly divided into two groups according to dietary hardness: normal diet group (pellet) and soft diet group (powder). In each group, the rabbits were further divided into four subgroups by feeding time: two weeks, four weeks, six weeks, and eight weeks. Animals would be injected 5-bromo-2′-deoxyuridine (BrdU) every day for one week before sacrificing. Histomorphometric analysis of MCC thickness was performed through haematoxylin and eosin (HE) staining. Immunochemical analysis was done to test BrdU and Notch-1. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to measure expression of Notch-1, Jagged-1, and Delta-like 1 (Dll-1).


Bone & Joint Research
Vol. 10, Issue 7 | Pages 380 - 387
5 Jul 2021
Shen J Sun D Fu J Wang S Wang X Xie Z

Aims

In contrast to operations performed for other fractures, there is a high incidence rate of surgical site infection (SSI) post-open reduction and internal fixation (ORIF) done for tibial plateau fractures (TPFs). This study investigates the effect of induced membrane technique combined with internal fixation for managing SSI in TPF patients who underwent ORIF.

Methods

From April 2013 to May 2017, 46 consecutive patients with SSI post-ORIF for TPFs were managed in our centre with an induced membrane technique. Of these, 35 patients were included for this study, with data analyzed in a retrospective manner.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 370 - 379
30 Jun 2021
Binder H Hoffman L Zak L Tiefenboeck T Aldrian S Albrecht C

Aims

The aim of this retrospective study was to determine if there are differences in short-term clinical outcomes among four different types of matrix-associated autologous chondrocyte transplantation (MACT).

Methods

A total of 88 patients (mean age 34 years (SD 10.03), mean BMI 25 kg/m2 (SD 3.51)) with full-thickness chondral lesions of the tibiofemoral joint who underwent MACT were included in this study. Clinical examinations were performed preoperatively and 24 months after transplantation. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Brittberg score, the Tegner Activity Scale, and the visual analogue scale (VAS) for pain. The Kruskal-Wallis test by ranks was used to compare the clinical scores of the different transplant types.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 388 - 400
8 Jul 2021
Dall’Ava L Hothi H Henckel J Di Laura A Tirabosco R Eskelinen A Skinner J Hart A

Aims

The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

Methods

We compared two groups, one made via 3D-printing (n = 7) and the other using conventional techniques (n = 7). We collected implant details, type of surgery and removal technique, patient demographics, and clinical history. Bone integration was assessed by macroscopic visual analysis, followed by sectioning to allow undecalcified histology on eight sections (~200 µm) for each implant. The outcome measures considered were area of bone attachment (%), extent of bone ingrowth (%), bone-implant contact (%), and depth of ingrowth (%), and these were quantified using a line-intercept method.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 203 - 217
1 Mar 2021
Wang Y Yin M Zhu S Chen X Zhou H Qian W

Patient-reported outcome measures (PROMs) are being used increasingly in total knee arthroplasty (TKA). We conducted a systematic review aimed at identifying psychometrically sound PROMs by appraising their measurement properties. Studies concerning the development and/or evaluation of the measurement properties of PROMs used in a TKA population were systematically retrieved via PubMed, Web of Science, Embase, and Scopus. Ratings for methodological quality and measurement properties were conducted according to updated COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Of the 155 articles on 34 instruments included, nine PROMs met the minimum requirements for psychometric validation and can be recommended to use as measures of TKA outcome: Oxford Knee Score (OKS); OKS–Activity and Participation Questionnaire (OKS-APQ); 12-item short form Knee Injury and Osteoarthritis Outcome (KOOS-12); KOOS Physical function Short form (KOOS-PS); Western Ontario and McMaster Universities Arthritis Index-Total Knee Replacement function short form (WOMAC-TKR); Lower Extremity Functional Scale (LEFS); Forgotten Joint Score (FJS); Patient’s Knee Implant Performance (PKIP); and University of California Los Angeles (UCLA) activity score. The pain and function subscales in WOMAC, as well as the pain, function, and quality of life subscales in KOOS, were validated psychometrically as standalone subscales instead of as whole instruments. However, none of the included PROMs have been validated for all measurement properties. Thus, further studies are still warranted to evaluate those PROMs. Use of the other 25 scales and subscales should be tempered until further studies validate their measurement properties.

Cite this article: Bone Joint Res 2021;10(3):203–217.


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 3 | Pages 188 - 191
1 Mar 2021
Nicholson T Scott A Newton Ede M Jones SW


Bone & Joint Research
Vol. 10, Issue 1 | Pages 10 - 21
1 Jan 2021
Zong Z Zhang X Yang Z Yuan W Huang J Lin W Chen T Yu J Chen J Cui L Li G Wei B Lin S

Aims

Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

Methods

Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 768 - 777
2 Nov 2020
Huang C Lu Y Hsu L Liau J Chang T Huang C

Aims

The material and design of knee components can have a considerable effect on the contact characteristics of the tibial post. This study aimed to analyze the stress distribution on the tibial post when using different grades of polyethylene for the tibial inserts. In addition, the contact properties of fixed-bearing and mobile-bearing inserts were evaluated.

Methods

Three different grades of polyethylene were compared in this study; conventional ultra high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (HXLPE), and vitamin E-stabilized polyethylene (VEPE). In addition, tibial baseplates with a fixed-bearing and a mobile-bearing insert were evaluated to understand differences in the contact properties. The inserts were implanted in neutral alignment and with a 10° internal malrotation. The contact stress, von Mises stress, and equivalent plastic strain (PEEQ) on the tibial posts were extracted for comparison.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 113 - 121
1 Feb 2021
Nicholson JA Oliver WM MacGillivray TJ Robinson CM Simpson AHRW

Aims

To evaluate if union of clavicle fractures can be predicted at six weeks post-injury by the presence of bridging callus on ultrasound.

Methods

Adult patients managed nonoperatively with a displaced mid-shaft clavicle were recruited prospectively. Ultrasound evaluation of the fracture was undertaken to determine if sonographic bridging callus was present. Clinical risk factors at six weeks were used to stratify patients at high risk of nonunion with a combination of Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) ≥ 40, fracture movement on examination, or absence of callus on radiograph.


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.