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Bone & Joint Research
Vol. 11, Issue 5 | Pages 292 - 300
13 May 2022
He C Chen C Jiang X Li H Zhu L Wang P Xiao T

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2022;11(5):292–300.


The Bone & Joint Journal
Vol. 102-B, Issue 2 | Pages 162 - 169
1 Feb 2020
Hoellwarth JS Tetsworth K Kendrew J Kang NV van Waes O Al-Maawi Q Roberts C Al Muderis M

Aims. Osseointegrated prosthetic limbs allow better mobility than socket-mounted prosthetics for lower limb amputees. Fractures, however, can occur in the residual limb, but they have rarely been reported. Approximately 2% to 3% of amputees with socket-mounted prostheses may fracture within five years. This is the first study which directly addresses the risks and management of periprosthetic osseointegration fractures in amputees. Methods. A retrospective review identified 518 osseointegration procedures which were undertaken in 458 patients between 2010 and 2018 for whom complete medical records were available. Potential risk factors including time since amputation, age at osseointegration, bone density, weight, uni/bilateral implantation and sex were evaluated with multiple logistic regression. The mechanism of injury, technique and implant that was used for fixation of the fracture, pre-osseointegration and post fracture mobility (assessed using the K-level) and the time that the prosthesis was worn for in hours/day were also assessed. Results. There were 22 periprosthetic fractures; they occurred exclusively in the femur: two in the femoral neck, 14 intertrochanteric and six subtrochanteric, representing 4.2% of 518 osseointegration operations and 6.3% of 347 femoral implants. The vast majority (19/22, 86.4%) occurred within 2 cm of the proximal tip of the implant and after a fall. No fractures occurred spontaneously. Fixation most commonly involved dynamic hip screws (10) and reconstruction plates (9). No osseointegration implants required removal, the K-level was not reduced after fixation of the fracture in any patient, and all retained a K-level of ≥ 2. All fractures united, 21 out of 22 patients (95.5%) wear their osseointegration-mounted prosthetic limb longer daily than when using a socket, with 18 out of 22 (81.8%) reporting using it for ≥ 16 hours daily. Regression analysis identified a 3.89-fold increased risk of fracture for females (p = 0.007) and a 1.02-fold increased risk of fracture per kg above a mean of 80.4 kg (p = 0.046). No increased risk was identified for bilateral implants (p = 0.083), time from amputation to osseointegration (p = 0.974), age at osseointegration (p = 0.331), or bone density (g/cm2, p = 0.560; T-score, p = 0.247; Z-score, p = 0.312). Conclusion. The risks and sequelae of periprosthetic fracture after press-fit osseointegration for amputation should not deter patients or clinicians from considering this procedure. Females and heavier patients are likely to have an increased risk of fracture. Age, years since amputation, and bone density do not appear influential. Cite this article: Bone Joint J 2020;102-B(2):162–169


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1017 - 1024
1 Sep 2022
Morris WZ Justo PGS Williams KA Kim Y Millis MB Novais EN

Aims

The aims of this study were to characterize the incidence and risk factors associated with stress fractures following periacetabular osteotomy, and to determine their effect on osteotomy union.

Methods

We retrospectively reviewed all periacetabular osteotomies (PAOs) performed for developmental dysplasia of the hip (DDH) at one institution over a six-year period between 2012 and 2017. Perioperative factors were recorded, and included demographic and surgical data. Postoperatively, patients were followed for a minimum of one year with anteroposterior and false profile radiographs of the pelvis to monitor for evidence of stress fracture and union of osteotomies. We characterized the incidence and locations of stress fractures, and used univariate and multivariable analysis to identify factors predictive of stress fracture and the association of stress fracture on osteotomy union.


Bone & Joint Research
Vol. 6, Issue 2 | Pages 82 - 89
1 Feb 2017
Nagra NS Zargar N Smith RDJ Carr AJ

Objectives. All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. Materials and Methods. A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05. Results. Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (. se). 17.6) compared with the all-suture anchors (mean 133.1 N . se. 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm . se. 2.5 versus 12.5 mm . se. 0.3; and 29.6 mm . se. 4.8 versus 17.0 mm . se. 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3). All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. Conclusion. We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon’s choice of implant, in the context of the clinical scenario. Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82–89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1


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.


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 820 - 825
1 Jul 2022
Dhawan R Baré JV Shimmin A

Aims

Adverse spinal motion or balance (spine mobility) and adverse pelvic mobility, in combination, are often referred to as adverse spinopelvic mobility (SPM). A stiff lumbar spine, large posterior standing pelvic tilt, and severe sagittal spinal deformity have been identified as risk factors for increased hip instability. Adverse SPM can create functional malposition of the acetabular components and hence is an instability risk. Adverse pelvic mobility is often, but not always, associated with abnormal spinal motion parameters. Dislocation rates for dual-mobility articulations (DMAs) have been reported to be between 0% and 1.1%. The aim of this study was to determine the early survivorship from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) of patients with adverse SPM who received a DMA.

Methods

A multicentre study was performed using data from 227 patients undergoing primary total hip arthroplasty (THA), enrolled consecutively. All the patients who had one or more adverse spine or pelvic mobility parameter had a DMA inserted at the time of their surgery. The mean age was 76 years (22 to 93) and 63% were female (n = 145). At a mean of 14 months (5 to 31) postoperatively, the AOANJRR was analyzed for follow-up information. Reasons for revision and types of revision were identified.


Bone & Joint Research
Vol. 11, Issue 5 | Pages 304 - 316
17 May 2022
Kim MH Choi LY Chung JY Kim E Yang WM

Aims

The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

Methods

The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed.


The Bone & Joint Journal
Vol. 104-B, Issue 6 | Pages 721 - 728
1 Jun 2022
Johansen A Ojeda-Thies C Poacher AT Hall AJ Brent L Ahern EC Costa ML

Aims

The aim of this study was to explore current use of the Global Fragility Fracture Network (FFN) Minimum Common Dataset (MCD) within established national hip fracture registries, and to propose a revised MCD to enable international benchmarking for hip fracture care.

Methods

We compared all ten established national hip fracture registries: England, Wales, and Northern Ireland; Scotland; Australia and New Zealand; Republic of Ireland; Germany; the Netherlands; Sweden; Norway; Denmark; and Spain. We tabulated all questions included in each registry, and cross-referenced them against the 32 questions of the MCD dataset. Having identified those questions consistently used in the majority of national audits, and which additional fields were used less commonly, we then used consensus methods to establish a revised MCD.


Objectives. Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes. Methods. Through a combined approach of gene expression analysis and web-based searching of NFAT1 binding sequences, 25 candidate target genes that displayed aberrant expression in Nfat1. -/-. AC at the initiation stage of OA, and possessed at least four NFAT1 binding sites in the promoter of each gene, were selected and tested for NFAT1 transcriptional activities by chromatin immunoprecipitation (ChIP) and promoter luciferase reporter assays using chondrocytes isolated from the AC of three- to four-month-old wild-type mice or Nfat1. -/-. mice with early OA phenotype. Results. Chromatin immunoprecipitation assays revealed that NFAT1 bound directly to the promoter of 21 of the 25 tested genes encoding cartilage-matrix proteins, growth factors, inflammatory cytokines, matrix-degrading proteinases, and specific transcription factors. Promoter luciferase reporter assays of representative anabolic and catabolic genes demonstrated that NFAT1-DNA binding functionally regulated the luciferase activity of specific target genes in wild-type chondrocytes, but not in Nfat1. -/-. chondrocytes or in wild-type chondrocytes transfected with plasmids containing mutated NFAT1 binding sequences. Conclusion. NFAT1 protects AC against degradation by directly regulating the transcription of target genes in articular chondrocytes. NFAT1 deficiency causes defective transcription of specific anabolic and catabolic genes in articular chondrocytes, leading to increased matrix catabolism and osteoarthritic cartilage degradation. Cite this article: M. Zhang, Q. Lu, T. Budden, J. Wang. NFAT1 protects articular cartilage against osteoarthritic degradation by directly regulating transcription of specific anabolic and catabolic genes. Bone Joint Res 2019;8:90–100. DOI: 10.1302/2046-3758.82.BJR-2018-0114.R1


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 1003 - 1008
1 Jul 2016
Fenton P Al-Nammari S Blundell C Davies M

Aims. Although infrequent, a fracture of the cuboid can lead to significant disruption of the integrity of the midfoot and its function. The purpose of this study was to classify the pattern of fractures of the cuboid, relate them to the mechanism of injury and suggest methods of managing them. Patients and Methods. We performed a retrospective review of patients with radiologically reported cuboid fractures. Fractures were grouped according to commonly occurring patterns of injury. A total of 192 fractures in 188 patients were included. They were classified into five patterns of injury. Results. Type 1 fractures (93 fractures, 48.4%) are simple avulsion injuries involving the capsule of the calcaneo-cuboid joint. Type 2 fractures (25 fractures, 13%) are isolated extra-articular injuries involving the body of the cuboid. Type 3 injuries (13 factures, 6.8%) are intra-articular fractures solely within the body of the cuboid. Type 4 fractures (35 fractures, 18.2%) are associated with disruption of the midfoot and tarsometatarsal injuries. Type 5 fractures (26 fractures, 13.5%) occur in conjunction with disruption of the mid-tarsal joint and either crushing of the lateral column alone or of both medial and lateral columns. Fractures with significant articular disruption or with loss of length of the lateral column underwent fixation. This involved either internal fixation to restore the anatomy of the cuboid and/or restoration of the length of the columns with bridging constructs using internal or external fixation. Conclusion. A classification system for fractures of the cuboid is proposed in relation to the mechanism of injury. The treatment of these fractures is described. Cite this article: Bone Joint J 2016;98-B:1003–8


Bone & Joint Open
Vol. 3, Issue 6 | Pages 495 - 501
14 Jun 2022
Keohane D Sheridan GA Masterson E

Aims

Total knee arthroplasty (TKA) is a common and safe orthopaedic procedure. Zimmer Biomet's NexGen is the second most popular brand of implant used in the UK. The primary cause of revision after the first year is aseptic loosening. We present our experience of using this implant, with significant concerns around its performance with regards early aseptic loosening of the tibial component.

Methods

A retrospective, single-surgeon review was carried out of all of the NexGen Legacy Posterior Stabilized (LPS) TKAs performed in this institute. The specific model used for the index procedures was the NexGen Complete Knee System (Legacy Knee-Posterior Stabilized LPS-Flex Articular Surface, LPS-Flex Femoral Component Option, and Stemmed Nonaugmentable Tibial Component Option).


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 922 - 928
1 Aug 2022
Png ME Petrou S Fernandez MA Achten J Parsons N McGibbon A Gould J Griffin XL Costa ML

Aims

The aim of this study was to compare the cost-effectiveness of cemented hemiarthroplasty (HA) versus hydroxyapatite-coated uncemented HA for the treatment of displaced intracapsular hip fractures in older adults.

Methods

A within-trial economic evaluation was conducted based on data collected from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized controlled trial in the UK. Resource use was measured over 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from the NHS and personal social service perspective. Methodological uncertainty was addressed using sensitivity analysis, while decision uncertainty was represented graphically using confidence ellipses and cost-effectiveness acceptability curves.


Bone & Joint 360
Vol. 11, Issue 4 | Pages 21 - 25
1 Aug 2022


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 980 - 986
1 Aug 2022
Ikram A Norrish AR Marson BA Craxford S Gladman JRF Ollivere BJ

Aims

We assessed the value of the Clinical Frailty Scale (CFS) in the prediction of adverse outcome after hip fracture.

Methods

Of 1,577 consecutive patients aged > 65 years with a fragility hip fracture admitted to one institution, for whom there were complete data, 1,255 (72%) were studied. Clinicians assigned CFS scores on admission. Audit personnel routinely prospectively completed the Standardised Audit of Hip Fracture in Europe form, including the following outcomes: 30-day survival; in-hospital complications; length of acute hospital stay; and new institutionalization. The relationship between the CFS scores and outcomes was examined graphically and the visual interpretations were tested statistically. The predictive values of the CFS and Nottingham Hip Fracture Score (NHFS) to predict 30-day mortality were compared using receiver operating characteristic area under the curve (AUC) analysis.


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.


The Bone & Joint Journal
Vol. 101-B, Issue 5 | Pages 522 - 528
1 May 2019
Medellin MR Fujiwara T Clark R Stevenson JD Parry M Jeys L

Aims. The aim of this study was to evaluate the prosthesis characteristics and associated conditions that may modify the survival of total femoral endoprosthetic replacements (TFEPR). Patients and Methods. In all, 81 patients treated with TFEPR from 1976 to 2017 were retrospectively evaluated and failures were categorized according to the Henderson classification. There were 38 female patients (47%) and 43 male patients (53%) with a mean age at diagnosis of 43 years (12 to 86). The mean follow-up time was 10.3 years (0 to 31.7). A survival analysis was performed followed by univariate and multivariate Cox regression to identify independent implant survival factors. Results. The revision-free survival of the implant was 71% at five years and 63.3% at ten years. Three prostheses reached 15 years without revision. The mean Musculoskeletal Tumor Society score in the group was 26 (23 to 28). The mechanisms of failure were infection in 18%, structural failures in 6%, tumour progression in 5%, aseptic loosening in 2%, and soft-tissue failures in 1%. Prostheses used for primary reconstruction after oncological resections had lower infection rates than revision implants (8% vs 25%; p = 0.001). The rates of infection in silver-coated and non-silver-coated prosthesis were similar (17.4% vs 19.%; p = 0.869). The incidence of hip dislocation was 10%. Rotating hinge prosthesis had a lower failure rate than fixed hinge prosthesis (5.3% vs 11%). After Cox regression, the independent factors associated with failures were the history of previous operations (hazard ratio (HR) 3.7; p = 0.041), and the associated arthroplasty of the proximal tibia (HR 3.8; p = 0.034). At last follow-up, 11 patients (13%) required amputation. Conclusion. TFEPR offers a reliable reconstruction option for massive bone loss of the femur, with a good survival when the prosthesis is used as a primary implant. The use of a rotating hinge at the knee and dual mobility bearing at the hip may be adequate to reduce the risk of mechanical and soft-tissue failures. Infection remains the main concern and there is insufficient evidence to support the routine use of silver-coated endoprosthesis. Cite this article: Bone Joint J 2019;101-B:522–528


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 987 - 996
1 Aug 2022

Aims

The aim of this study was to describe the demographic details of patients who sustain a femoral periprosthetic fracture (PPF), the epidemiology of PPFs, PPF characteristics, and the predictors of PPF types in the UK population.

Methods

This is a multicentre retrospective cohort study including adult patients presenting to hospital with a new PPF between 1 January 2018 and 31 December 2018. Data collected included: patient characteristics, comorbidities, anticoagulant use, social circumstances, level of mobility, fracture characteristics, Unified Classification System (UCS) type, and details of the original implant. Descriptive analysis by fracture location was performed, and predictors of PPF type were assessed using mixed-effects logistic regression models.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 494 - 502
20 Jul 2022
Kwon HM Lee J Koh Y Park KK Kang K

Aims

A functional anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) has been assumed to be required for patients undergoing unicompartmental knee arthroplasty (UKA). However, this assumption has not been thoroughly tested. Therefore, this study aimed to assess the biomechanical effects exerted by cruciate ligament-deficient knees with medial UKAs regarding different posterior tibial slopes.

Methods

ACL- or PCL-deficient models with posterior tibial slopes of 1°, 3°, 5°, 7°, and 9° were developed and compared to intact models. The kinematics and contact stresses on the tibiofemoral joint were evaluated under gait cycle loading conditions.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 349 - 361
9 Jun 2022
Jun Z Yuping W Yanran H Ziming L Yuwan L Xizhong Z Zhilin W Xiaoji L

Aims

The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

Methods

HAAM scaffolds were constructed via trypsinization from fresh human amniotic membrane (HAM). The characteristics of the HAAM scaffolds were evaluated by haematoxylin and eosin (H&E) staining, picrosirius red staining, type II collagen immunostaining, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Human amniotic mesenchymal stem cells (hAMSCs) were isolated, and stemness was verified by multilineage differentiation. Then, third-generation (P3) hAMSCs were seeded on the HAAM scaffolds, and phalloidin staining and SEM were used to detect the growth of hAMSCs on the HAAM scaffolds. Osteochondral defects (diameter: 3.5 mm; depth: 3 mm) were created in the right patellar grooves of 20 New Zealand White rabbits. The rabbits were randomly divided into four groups: the control group (n = 5), the HAAM scaffolds group (n = 5), the JCFs group (n = 5), and the HAAM + JCFs group (n = 5). Macroscopic and histological assessments of the regenerated tissue were evaluated to validate the treatment results at 12 weeks.