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Bone & Joint Research
Vol. 13, Issue 1 | Pages 1 - 3
1 Jan 2024
Simpson AHRW


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 38 - 38
17 Nov 2023
Al-Namnam NM Luczak AT Collishaw S Li X Lucas M Simpson AHRW
Full Access

Abstract

Introduction

Ultrasonic cutting in surgery has great potential. However, a key limitation is heat created by friction between the bone and the blade. Bone has poor thermal conductivity which hinders the dissipation of heat, causing cell death near the cut site In addition, ultrasonic vibration may create microcracks. It was hypothesised that these effects on bone would vary with the frequency and displacement of the ultrasonically powered blade. Therefore varying frequencies and displacements of the tip of the blade were studied to find the combination with fewest microcracks and lowest temperature rise at the bone-tool interface.

Aim

To explore the effect of different frequencies and tip displacements of ultrasonic cutting devices on the amount of thermal and mechanical damage.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 654 - 656
16 Oct 2023
Makaram NS Simpson AHRW

Cite this article: Bone Joint Res 2023;12(10):654–656.


Cite this article: Bone Joint Res 2023;12(9):598–600.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 494 - 496
9 Aug 2023
Clement ND Simpson AHRW

Cite this article: Bone Joint Res 2023;12(8):494–496.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 372 - 374
8 Jun 2023
Makaram NS Lamb SE Simpson AHRW

Cite this article: Bone Joint Res 2023;12(6):372–374.


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 365 - 372
15 Mar 2023
Yapp LZ Scott CEH MacDonald DJ Howie CR Simpson AHRW Clement ND

Aims

This study investigates whether primary knee arthroplasty (KA) restores health-related quality of life (HRQoL) to levels expected in the general population.

Methods

This retrospective case-control study compared HRQoL data from two sources: patients undergoing primary KA in a university-teaching hospital (2013 to 2019), and the Health Survey for England (HSE; 2010 to 2012). Patient-level data from the HSE were used to represent the general population. Propensity score matching was used to balance covariates and facilitate group comparisons. A propensity score was estimated using logistic regression based upon the covariates sex, age, and BMI. Two matched cohorts with 3,029 patients each were obtained for the adjusted analyses (median age 70.3 (interquartile range (IQR) 64 to 77); number of female patients 3,233 (53.4%); median BMI 29.7 kg/m2 (IQR 26.5 to 33.7)). HRQoL was measured using the three-level version of the EuroQol five-dimension questionnaire (EQ-5D-3L), and summarized using the Index and EuroQol visual analogue scale (EQ-VAS) scores.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 1 - 4
1 Jan 2023
Simpson AHRW


Bone & Joint Research
Vol. 11, Issue 12 | Pages 890 - 892
1 Dec 2022
Farrow L Jenkins PJ Dunstan E Murray A Blyth MJG Simpson AHRW Clement ND

Cite this article: Bone Joint Res 2022;11(12):890–892.


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1313 - 1322
1 Dec 2022
Yapp LZ Clement ND Moran M Clarke JV Simpson AHRW Scott CEH

Aims

The aim of this study was to assess factors associated with the estimated lifetime risk of revision surgery after primary knee arthroplasty (KA).

Methods

All patients from the Scottish Arthroplasty Project dataset undergoing primary KA during the period 1 January 1998 to 31 December 2019 were included. The cumulative incidence function for revision and death was calculated up to 20 years. Adjusted analyses used cause-specific Cox regression modelling to determine the influence of patient factors. The lifetime risk was calculated as a percentage for patients aged between 45 and 99 years using multiple-decrement life table methodology.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 619 - 628
7 Sep 2022
Yapp LZ Scott CEH Howie CR MacDonald DJ Simpson AHRW Clement ND

Aims

The aim of this study was to report the meaningful values of the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) and EuroQol visual analogue scale (EQ-VAS) in patients undergoing primary knee arthroplasty (KA).

Methods

This is a retrospective study of patients undergoing primary KA for osteoarthritis in a university teaching hospital (Royal Infirmary of Edinburgh) (1 January 2013 to 31 December 2019). Pre- and postoperative (one-year) data were prospectively collected for 3,181 patients (median age 69.9 years (interquartile range (IQR) 64.2 to 76.1); females, n = 1,745 (54.9%); median BMI 30.1 kg/m2 (IQR 26.6 to 34.2)). The reliability of the EQ-5D-3L was measured using Cronbach’s alpha. Responsiveness was determined by calculating the anchor-based minimal clinically important difference (MCID), the minimal important change (MIC) (cohort and individual), the patient-acceptable symptom state (PASS) predictive of satisfaction, and the minimal detectable change at 90% confidence intervals (MDC-90).


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 6 | Pages 409 - 412
22 Jun 2022
Tsang SJ Ferreira N Simpson AHRW


Bone & Joint Research
Vol. 11, Issue 6 | Pages 346 - 348
1 Jun 2022
Hall AJ Clement ND MacLullich AMJ Simpson AHRW Johansen A White TO Duckworth AD


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. 11, Issue 5 | Pages 301 - 303
17 May 2022
Clement ND Skinner JA Haddad FS Simpson AHRW


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 321 - 330
1 Mar 2022
Brzeszczynski F Brzeszczynska J Duckworth AD Murray IR Simpson AHRW Hamilton DF

Aims

Sarcopenia is characterized by a generalized progressive loss of skeletal muscle mass, strength, and physical performance. This systematic review primarily evaluated the effects of sarcopenia on postoperative functional recovery and mortality in patients undergoing orthopaedic surgery, and secondarily assessed the methods used to diagnose and define sarcopenia in the orthopaedic literature.

Methods

A systematic search was conducted in MEDLINE, EMBASE, and Google Scholar databases according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies involving sarcopenic patients who underwent defined orthopaedic surgery and recorded postoperative outcomes were included. The quality of the criteria by which a diagnosis of sarcopenia was made was evaluated. The quality of the publication was assessed using Newcastle-Ottawa Scale.


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


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 45 - 52
1 Jan 2022
Yapp LZ Clement ND Moran M Clarke JV Simpson AHRW Scott CEH

Aims

The aim of this study was to determine the long-term mortality rate, and to identify factors associated with this, following primary and revision knee arthroplasty (KA).

Methods

Data from the Scottish Arthroplasty Project (1998 to 2019) were retrospectively analyzed. Patient mortality data were linked from the National Records of Scotland. Analyses were performed separately for the primary and revised KA cohorts. The standardized mortality ratio (SMR) with 95% confidence intervals (CIs) was calculated for the population at risk. Multivariable Cox proportional hazards were used to identify predictors and estimate relative mortality risks.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 840 - 843
15 Dec 2021
Al-Hourani K Tsang SJ Simpson AHRW


Bone & Joint Research
Vol. 10, Issue 12 | Pages 830 - 839
15 Dec 2021
Robertson G Wallace R Simpson AHRW Dawson SP

Aims

Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning.

Methods

A total of 54 patients with distal radial fractures were included in the study. Each underwent posteroanterior (PA) and lateral radiographs of the injured wrist with an aluminium step wedge. Overall 27 patients underwent routine DXA scanning of the hip and lumbar spine, with 13 undergoing additional DXA scanning of the uninjured forearm. Analysis of radiographs was performed on ImageJ and Matlab with calculations of cortical measures, cortical indices, combined cortical scores, and aluminium equivalent grading.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 759 - 766
1 Dec 2021
Nicholson JA Oliver WM MacGillivray TJ Robinson CM Simpson AHRW

Aims

The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus.

Methods

A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC).


Bone & Joint Research
Vol. 10, Issue 9 | Pages 591 - 593
7 Sep 2021
Thompson JW Simpson AHRW Haddad FS


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1514 - 1525
1 Sep 2021
Scott CEH Holland G Gillespie M Keenan OJ Gherman A MacDonald DJ Simpson AHRW Clement ND

Aims

The aims of this study were to investigate the ability to kneel after total knee arthroplasty (TKA) without patellar resurfacing, and its effect on patient-reported outcome measures (PROMs). Secondary aims included identifying which kneeling positions were most important to patients, and the influence of radiological parameters on the ability to kneel before and after TKA.

Methods

This prospective longitudinal study involved 209 patients who underwent single radius cruciate-retaining TKA without patellar resurfacing. Preoperative EuroQol five-dimension questionnaire (EQ-5D), Oxford Knee Score (OKS), and the ability to achieve four kneeling positions were assessed including a single leg kneel, a double leg kneel, a high-flexion kneel, and a praying position. The severity of radiological osteoarthritis (OA) was graded and the pattern of OA was recorded intraoperatively. The flexion of the femoral component, posterior condylar offset, and anterior femoral offset were measured radiologically. At two to four years postoperatively, 151 patients with a mean age of 70.0 years (SD 9.44) were included. Their mean BMI was 30.4 kg/m2 (SD 5.36) and 60 were male (40%). They completed EQ-5D, OKS, and Kujala scores, assessments of the ability to kneel, and a visual analogue scale for anterior knee pain and satisfaction.


Bone & Joint Open
Vol. 2, Issue 7 | Pages 522 - 529
13 Jul 2021
Nicholson JA Clement ND Clelland AD MacDonald DJ Simpson AHRW Robinson CM

Aims

It is unclear whether acute plate fixation facilitates earlier return of normal shoulder function following a displaced mid-shaft clavicular fracture compared with nonoperative management when union occurs. The primary aim of this study was to establish whether acute plate fixation was associated with a greater return of normal shoulder function when compared with nonoperative management in patients who unite their fractures. The secondary aim was to investigate whether there were identifiable predictors associated with return of normal shoulder function in patients who achieve union with nonoperative management.

Methods

Patient data from a randomized controlled trial were used to compare acute plate fixation with nonoperative management of united fractures. Return of shoulder function was based on the age- and sex-matched Disabilities of the Arm, Shoulder and Hand (DASH) scores for the cohort. Independent predictors of an early recovery of normal shoulder function were investigated using a separate prospective series of consecutive nonoperative displaced mid-shaft clavicular fractures recruited over a two-year period (aged ≥ 16 years). Patient demographics and functional recovery were assessed over the six months post-injury using a standardized protocol.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_7 | Pages 4 - 4
1 May 2021
Nicholson JA Oliver WM Gillespie M Simpson AHRW White TO Duckworth AD
Full Access

Non-operative management of displaced olecranon fractures in elderly low demand patients is reported to result in a satisfactory outcome despite routinely producing a nonunion. The aim of this study was to assess whether there is evidence of dynamic movement of the fracture fragment during the elbow arc of movement.

Five consecutive patients (≥70 years of age) with a displaced olecranon fracture (Mayo 2A) that were managed with non-operative intervention were recruited. All underwent ultrasound evaluation at six weeks and follow-up questionnaires at six months including the DASH and Oxford Elbow Score (OES).

There were three women and two men with a mean age of 79yrs (range 70–88). All injuries were sustained following a fall from standing height. The mean fracture gap in extension was 22.5mm (95% CI 13.0–31.9), midflexion 21.8mm (11.6–32.0) and in deep flexion 21.8mm (10.9–32.8). Although the amount of fracture displacement varied between patients, it remained static in each patient with no significant differences observed throughout the arc of motion (ANOVA p=0.99). The six-month median DASH score was 7.5 (IQR range, 4.2–39.3) and the OES was 44.0 (29.0–47.5). Four out of the five patients were satisfied with their function.

Ultrasound evaluation of displaced olecranon fractures following non-operative management suggests the proximal fragment may function as a sesamoid type bone within the triceps sleeve. This could explain how a functional arc of movement with a minimum level of discomfort can usually be expected with non-operative management in select patients.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_8 | Pages 8 - 8
1 May 2021
Yapp LZ Walmsley PJ Moran M Clarke JV Simpson AHRW Scott CEH
Full Access

The aim of this study was to measure the effect of hospital case-volume on the survival of revision total knee arthroplasty (RTKA).

A retrospective analysis of Scottish Arthroplasty Project data was performed. The primary outcome was RTKA survival at ten years. The primary explanatory variable was annual hospital case-volume. Kaplan-Meier survival curves were plotted with 95% confidence intervals (CI) to determine the lifespan of RTKA. Multivariable Cox proportional hazards were used to estimate relative revision risks over time.

From 1998 to 2019, 8894 patients underwent RTKA surgery in Scotland (median age 70 years, median follow-up 6.2 years, 4789 (53.5%) females; 718 (8.8%) for infection). Of these patients, 957 (10.8%) underwent a second revision procedure on their knee. Male sex, younger age at index revision, and positive infection status were associated with need for re-revision. The ten-year survival estimate for RTKA was 87.3% (95%CI 86.5–88.1). Adjusting for gender, age, surgeon volume and infection status, increasing hospital case-volume was significantly associated with lower risk of re-revision (Hazard Ratio 0.78 (0.64–0.94, p<0.001)). The risk of re-revision steadily declined in centres performing >20 cases per year: relative risk reduction 16% with >20 cases; 22% with >30 cases; and 28% with >40 cases.

The majority of RTKA in Scotland survive up to ten years. Increasing yearly hospital case-volume above 20 cases is independently associated with a significant risk reduction of re-revision. Development of high-volume tertiary centres may lead to an improvement in the overall survival of RTKA.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_7 | Pages 5 - 5
1 May 2021
Jalal MMK Wallace RJ Peault B Simpson AHRW
Full Access

The role of mesenchymal stem cells (MSCs) in enhancing healing process has been examined with allogeneic and xenogeneic cells in transplantation models. However, certain factors might limit the use of allogeneic cells in clinical practice, (e.g. disease transmission, ethical issues and patient acceptance). Adipose tissue represents an abundant source for autologous cells. The aim of this study was to evaluate adipose-derived autologous cells for preventing non-union.

Adults male Wistar rats (n=5) underwent a previously published surgical procedure known to result in non-union if no treatment is given. This consisted of a mid-shaft tibial osteotomy with peri/endosteal stripping stabilised by intramedullary nail fixation with a 1mm gap maintained by a spacer. During the same operation, ipsilateral inguinal subcutaneous fat was harvested and processed for cell isolation. After three weeks in culture, the cell number reached 5×106 and were injected into the fracture site.

At the end of the experiment, all tibias (injected with autologous fat-MSCs) developed union. These were compared with a control group injected with PBS (n=4) and with allogenic (n=5) and xenogeneic (n=6) cell transplantation groups. The amount of callus was noticeably large in the autologous cell group and the distal-callus index was significantly greater than that of the other groups, P-value =<0.05, unpaired t-test, corrected by Benjamini & Hochberg.

We report a novel method for autologous MSCs implantation to stimulate fracture healing. Local injection of autologous fat-MSCs into the fracture site resulted in a solid union in all the tibias with statistically significantly greater amounts of callus.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_8 | Pages 9 - 9
1 May 2021
Nicholson JA Oliver WM Perks F Macgillivray T Robinson CM Simpson AHRW
Full Access

Sonographic callus may enable assessment of fracture healing. The aim of this study was to establish a reliable method for three-dimensional reconstruction of sonographic callus.

Patients that underwent non-operative management of displaced midshaft clavicle fractures and intramedullary nailing of tibia fractures were prospectively recruited and followed to union. Ultrasound scanning was performed at periodical time points following injury. Infra-red tracking technology was used to map each image to a three-dimensional lattice. Criteria was fist established for two-dimensional bridging callus detection in a pilot study. Using echo intensity of the ultrasound image, semi-automated mapping was used to create an anatomic three-dimensional representation of fracture healing. Agreement on the presence of sonographic bridging callus was assessed using the kappa coefficient and intra-class-correlation (ICC) between observers.

112 clavicle fractures and 10 tibia fractures completed follow-up at six months. Sonographic bridging callus was detected in 62.5% (n=70/112) of the clavicles at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n=69/70). If absent, nonunion developed in 40.5% of cases (n=17/42)(73.4%-sensitive and 100%-specific to predict union). Out of 10 tibia fractures, 7 had bridging callus of at least one cortex at 6 weeks and when present all united. Of the three patients lacking sonographic bridging callus, one went onto a nonunion (77.8%-sensitive and 100%-specific to predict union). The ICC for sonographic callus between four reviewers was 0.82 (95% CI 0.68–0.91)

Three-dimensional ultrasound reconstruction of bridging callus has the potential to identify impaired fracture healing at an early stage in fracture management.


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 602 - 609
1 Apr 2021
Yapp LZ Walmsley PJ Moran M Clarke JV Simpson AHRW Scott CEH

Aims

The aim of this study was to measure the effect of hospital case volume on the survival of revision total knee arthroplasty (RTKA).

Methods

This is a retrospective analysis of Scottish Arthroplasty Project data, a nationwide audit which prospectively collects data on all arthroplasty procedures performed in Scotland. The primary outcome was RTKA survival at ten years. The primary explanatory variable was the effect of hospital case volume per year on RTKA survival. Kaplan-Meier survival curves were plotted with 95% confidence intervals (CIs) to determine the lifespan of RTKA. Multivariate Cox proportional hazards were used to estimate relative revision risks over time. Hazard ratios (HRs) were reported with 95% CI, and p-value < 0.05 was considered statistically significant.


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 600 - 601
1 Apr 2021
Yapp LZ Walmsley PJ Moran M Clarke JV Simpson AHRW Scott CEH


Bone & Joint Open
Vol. 2, Issue 3 | Pages 203 - 210
19 Mar 2021
Yapp LZ Clarke JV Moran M Simpson AHRW Scott CEH

Aims

The COVID-19 pandemic led to a national suspension of “non-urgent” elective hip and knee arthroplasty. The study aims to measure the effect of the COVID-19 pandemic on total hip arthroplasty (THA) and total knee arthroplasty (TKA) volume in Scotland. Secondary objectives are to measure the success of restarting elective services and model the time required to bridge the gap left by the first period of suspension.

Methods

A retrospective observational study using the Scottish Arthroplasty Project dataset. All patients undergoing elective THAs and TKAs during the period 1 January 2008 to 31 December 2020 were included. A negative binomial regression model using historical case-volume and mid-year population estimates was built to project the future case-volume of THA and TKA in Scotland. The median monthly case volume was calculated for the period 2008 to 2019 (baseline) and compared to the actual monthly case volume for 2020. The time taken to eliminate the deficit was calculated based upon the projected monthly workload and with a potential workload between 100% to 120% of baseline.


Bone & Joint Open
Vol. 2, Issue 2 | Pages 79 - 85
15 Feb 2021
Downie S Stillie A Moran M Sudlow C Simpson AHRW

Aims

Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD.

Methods

This will be a prospective, longitudinal study across six UK orthopaedic centres powered to identify the influence of ten patient variables on quality of life at three months after surgery for MBD. Adult patients managed for bone metastases will be screened by their treating consultant and posted out participant materials. If they opt in to participate, they will receive questionnaire packs at regular intervals from three to 24 months post-surgery and their electronic records will be screened until death or five years from recruitment. The primary outcome is quality of life as measured by the European Organisation for Research and the Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) C30 questionnaire. The protocol has been approved by the Newcastle & North Tyneside 2 Research Ethics Committee (REC ref 19/NE/0303) and the study is funded by the Royal College of Physicians and Surgeons of Glasgow (RCPSG) and the Association for Cancer Surgery (BASO-ACS).


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 12 | Pages 870 - 872
21 Dec 2020
Tsang SJ Simpson AHRW


Bone & Joint Research
Vol. 9, Issue 12 | Pages 873 - 883
8 Dec 2020
Clement ND Ng N Simpson CJ Patton RFL Hall AJ Simpson AHRW Duckworth AD

Aims

The aims of this meta-analysis were to assess: 1) the prevalence of coronavirus disease 2019 (COVID-19) in hip fracture patients; 2) the associated mortality rate and risk associated with COVID-19; 3) the patient demographics associated with COVID-19; 4) time of diagnosis; and 5) length of follow-up after diagnosis of COVID-19.

Methods

Searches of PubMed, Medline, and Google Scholar were performed in October 2020 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Search terms included “hip”, “fracture”, and “COVID-19”. The criteria for inclusion were published clinical articles reporting the mortality rate associated with COVID-19 in hip fracture patients. In total, 53 articles were identified and following full text screening 28 articles satisfied the inclusion criteria.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 798 - 807
2 Nov 2020
Brzeszczyńska J Brzeszczyński F Hamilton DF McGregor R Simpson AHRW

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data.

Cite this article: Bone Joint Res 2020;9(11):798–807.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1274 - 1276
3 Oct 2020
Tsang SJ Eyre DW Atkins BL Simpson AHRW


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1271 - 1273
1 Oct 2020
Scott CEH Simpson AHRW Pankaj P


Bone & Joint Research
Vol. 9, Issue 6 | Pages 311 - 313
1 Jun 2020
Tsang SJ Morgan-Jones R Simpson AHRW


Bone & Joint Research
Vol. 9, Issue 4 | Pages 200 - 201
1 Apr 2020
Simpson AHRW Dall G Haas JG


The Bone & Joint Journal
Vol. 102-B, Issue 4 | Pages 434 - 441
1 Apr 2020
Hamilton DF Burnett R Patton JT MacPherson GJ Simpson AHRW Howie CR Gaston P

Aims

There are comparatively few randomized studies evaluating knee arthroplasty prostheses, and fewer still that report longer-term functional outcomes. The aim of this study was to evaluate mid-term outcomes of an existing implant trial cohort to document changing patient function over time following total knee arthroplasty using longitudinal analytical techniques and to determine whether implant design chosen at time of surgery influenced these outcomes.

Methods

A mid-term follow-up of the remaining 125 patients from a randomized cohort of total knee arthroplasty patients (initially comprising 212 recruited patients), comparing modern (Triathlon) and traditional (Kinemax) prostheses was undertaken. Functional outcomes were assessed with the Oxford Knee Score (OKS), knee range of movement, pain numerical rating scales, lower limb power output, timed functional assessment battery, and satisfaction survey. Data were linked to earlier assessment timepoints, and analyzed by repeated measures analysis of variance (ANOVA) mixed models, incorporating longitudinal change over all assessment timepoints.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 304 - 312
1 Jul 2019
Nicholson JA Tsang STJ MacGillivray TJ Perks F Simpson AHRW

Objectives

The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.

Methods

A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 62 - 62
1 Nov 2018
Tsang STJ Gwynne PJ Gallagher MP Simpson AHRW
Full Access

Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged by a low-intensity ultrasound (1.5MHz, 30mW/cm2, pulse duration 200µs/1KHz) for 20 minutes and gentamicin. The outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was 64mg/L. Low intensity pulsed ultrasound was associated with a 4-fold reduction in the effective biofilm eradication concentration of gentamicin; bringing the MBEC of gentamicin to within clinically achievable concentrations.


The Bone & Joint Journal
Vol. 100-B, Issue 11 | Pages 1407 - 1408
1 Nov 2018
Simpson AHRW Frost H Norrie J


Bone & Joint Research
Vol. 7, Issue 9 | Pages 539 - 540
5 Sep 2018
Murray IR Geeslin AG Chahla J Murray AD Goudie EB Petrigliano FA Simpson AHRW LaPrade RF


Bone & Joint Research
Vol. 7, Issue 8 | Pages 517 - 523
1 Aug 2018
Tsang STJ Gwynne PJ Gallagher MP Simpson AHRW

Objectives

Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time.

Materials and Methods

Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 minutes, 180 minutes, and 24 hours.


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

Objectives

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

Methods

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


Bone & Joint Research
Vol. 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.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 79 - 84
1 Jan 2018
Tsang STJ McHugh MP Guerendiain D Gwynne PJ Boyd J Simpson AHRW Walsh TS Laurenson IF Templeton KE

Objectives

Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients.

Methods

Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery.


Objectives

Secondary fracture healing is strongly influenced by the stiffness of the bone-fixator system. Biomechanical tests are extensively used to investigate stiffness and strength of fixation devices. The stiffness values reported in the literature for locked plating, however, vary by three orders of magnitude. The aim of this study was to examine the influence that the method of restraint and load application has on the stiffness produced, the strain distribution within the bone, and the stresses in the implant for locking plate constructs.

Methods

Synthetic composite bones were used to evaluate experimentally the influence of four different methods of loading and restraining specimens, all used in recent previous studies. Two plate types and three screw arrangements were also evaluated for each loading scenario. Computational models were also developed and validated using the experimental tests.


The Bone & Joint Journal
Vol. 99-B, Issue 12 | Pages 1559 - 1560
1 Dec 2017
Murray IR Murray AD Wordie SJ Oliver CW Simpson AHRW Haddad FS


The Bone & Joint Journal
Vol. 99-B, Issue 12 | Pages 1557 - 1558
1 Dec 2017
Murray IR Murray AD Wordie SJ Oliver CW Simpson AHRW Haddad FS


The Bone & Joint Journal
Vol. 99-B, Issue 12 | Pages 1555 - 1556
1 Dec 2017
Amin AK Simpson AHRW Hall AC


Bone & Joint Research
Vol. 6, Issue 11 | Pages 619 - 620
1 Nov 2017
Murray IR Murray AD Wordie SJ Oliver CW Murray AW Simpson AHRW


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1458 - 1466
1 Nov 2017
Tsang SJ Ting J Simpson AHRW Gaston P

Aims

The aims of the study were to review and analyse the reported series of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip arthroplasties (THAs) to establish the overall success and the influencing factors.

Patients and methods

Using a standardised recognised study protocol, meta-analysis of observational studies in epidemiology guidelines, a comprehensive review and analysis of the literature was performed. The primary outcome measure was the success of treatment. The search strategy and inclusion criteria which involved an assessment of quality yielded 39 articles for analysis, which included 1296 patients.


Bone & Joint Research
Vol. 6, Issue 10 | Pages 610 - 611
1 Oct 2017
Simpson AHRW


The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 494 - 502
1 Apr 2017
Simpson AHRW Keenan G Nayagam S Atkins RM Marsh D Clement ND

Aims

The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis.

Patients and Methods

A total of 62 adult patients undergoing limb lengthening or bone transport by distraction osteogenesis were randomised to treatment with either an active (n = 32) or a placebo (n = 30) ultrasound device. A standardised corticotomy was performed in the proximal tibial metaphysis and a circular Ilizarov frame was used in all patients. The rate of distraction was also standardised. The primary outcome measure was the time to removal of the frame after adjusting for the length of distraction in days/cm for both the per protocol (PP) and the intention-to-treat (ITT) groups. The assessor was blinded to the form of treatment. A secondary outcome was to identify covariates affecting the time to removal of the frame.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 194 - 195
1 Apr 2017
Simpson AHRW Howie CR Norrie J


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 218 - 224
1 Feb 2017
Hamilton DF Loth FL Giesinger JM Giesinger K MacDonald DJ Patton JT Simpson AHRW Howie CR

Aims

To validate the English language Forgotten Joint Score-12 (FJS-12) as a tool to evaluate the outcome of hip and knee arthroplasty in a United Kingdom population.

Patients and Methods

All patients undergoing surgery between January and August 2014 were eligible for inclusion. Prospective data were collected from 205 patients undergoing total hip arthroplasty (THA) and 231 patients undergoing total knee arthroplasty (TKA). Outcomes were assessed with the FJS-12 and the Oxford Hip and Knee Scores (OHS, OKS) pre-operatively, then at six and 12 months post-operatively. Internal consistency, convergent validity, effect size, relative validity and ceiling effects were determined.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 520 - 522
1 Oct 2016
Simpson AHRW Murray IR Duckworth AD


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

Objectives

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

Methods

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


Bone & Joint Research
Vol. 5, Issue 4 | Pages 116 - 121
1 Apr 2016
Leow JM Clement ND Tawonsawatruk T Simpson CJ Simpson AHRW

Objectives

The radiographic union score for tibial (RUST) fractures was developed by Whelan et al to assess the healing of tibial fractures following intramedullary nailing. In the current study, the repeatability and reliability of the RUST score was evaluated in an independent centre (a) using the original description, (b) after further interpretation of the description of the score, and (c) with the immediate post-operative radiograph available for comparison.

Methods

A total of 15 radiographs of tibial shaft fractures treated by intramedullary nailing (IM) were scored by three observers using the RUST system. Following discussion on how the criteria of the RUST system should be implemented, 45 sets (i.e. AP and lateral) of radiographs of IM nailed tibial fractures were scored by five observers. Finally, these 45 sets of radiographs were rescored with the baseline post-operative radiograph available for comparison.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 137 - 144
1 Apr 2016
Paterson SI Eltawil NM Simpson AHRW Amin AK Hall AC

Objectives

During open orthopaedic surgery, joints may be exposed to air, potentially leading to cartilage drying and chondrocyte death, however, the long-term effects of joint drying in vivo are poorly understood. We used an animal model to investigate the subsequent effects of joint drying on cartilage and chondrocytes.

Methods

The patellar groove of anaesthetised rats was exposed (sham-operated), or exposed and then subjected to laminar airflow (0.25m/s; 60 minutes) before wounds were sutured and animals recovered. Animals were monitored for up to eight weeks and then sacrificed. Cartilage and chondrocyte properties were studied by histology and confocal microscopy, respectively.


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 534 - 541
1 Apr 2016
Tsang STJ Mills LA Frantzias J Baren JP Keating JF Simpson AHRW

Aims

The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures.

Patients and Methods

A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 months).

The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union.

Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union.


Bone & Joint Research
Vol. 5, Issue 3 | Pages 87 - 91
1 Mar 2016
Hamilton DF Giesinger JM MacDonald DJ Simpson AHRW Howie CR Giesinger K

Objectives

To assess the responsiveness and ceiling/floor effects of the Forgotten Joint Score -12 and to compare these with that of the more widely used Oxford Hip Score (OHS) in patients six and 12 months after primary total hip arthroplasty.

Methods

We prospectively collected data at six and 12 months following total hip arthroplasty from 193 patients undergoing surgery at a single centre. Ceiling effects are outlined with frequencies for patients obtaining the lowest or highest possible score. Change over time from six months to 12 months post-surgery is reported as effect size (Cohen’s d).


Bone & Joint Research
Vol. 5, Issue 2 | Pages 61 - 65
1 Feb 2016
Scott EEF Hamilton DF Wallace RJ Muir AY Simpson AHRW

Objectives

Temperature is known to influence muscle physiology, with the velocity of shortening, relaxation and propagation all increasing with temperature. Scant data are available, however, regarding thermal influences on energy required to induce muscle damage.

Methods

Gastrocnemius and soleus muscles were harvested from 36 male rat limbs and exposed to increasing impact energy in a mechanical test rig. Muscle temperature was varied in 5°C increments, from 17°C to 42°C (to encompass the in vivo range). The energy causing non-recoverable deformation was recorded for each temperature. A measure of tissue elasticity was determined via accelerometer data, smoothed by low-pass fifth order Butterworth filter (10 kHz). Data were analysed using one-way analysis of variance (ANOVA) and significance was accepted at p = 0.05.


Bone & Joint Research
Vol. 4, Issue 12 | Pages 195 - 197
1 Dec 2015
Simpson AHRW Dave J Ghert M


Bone & Joint Research
Vol. 4, Issue 9 | Pages 152 - 153
1 Sep 2015
Hamilton DF Ghert M Simpson AHRW


Bone & Joint Research
Vol. 4, Issue 8 | Pages 137 - 144
1 Aug 2015
Hamilton DF Giesinger JM Patton JT MacDonald DJ Simpson AHRW Howie CR Giesinger K

Objectives

The Oxford Hip and Knee Scores (OHS, OKS) have been demonstrated to vary according to age and gender, making it difficult to compare results in cohorts with different demographics. The aim of this paper was to calculate reference values for different patient groups and highlight the concept of normative reference data to contextualise an individual’s outcome.

Methods

We accessed prospectively collected OHS and OKS data for patients undergoing lower limb joint arthroplasty at a single orthopaedic teaching hospital during a five-year period. T-scores were calculated based on the OHS and OKS distributions.


Bone & Joint Research
Vol. 4, Issue 7 | Pages 117 - 119
1 Jul 2015
Simpson AHRW


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 723 - 728
1 Jun 2015
Hamilton DF Howie CR Burnett R Simpson AHRW Patton JT

Worldwide rates of primary and revision total knee arthroplasty (TKA) are rising due to increased longevity of the population and the burden of osteoarthritis.

Revision TKA is a technically demanding procedure generating outcomes which are reported to be inferior to those of primary knee arthroplasty, and with a higher risk of complication. Overall, the rate of revision after primary arthroplasty is low, but the number of patients currently living with a TKA suggests a large potential revision healthcare burden.

Many patients are now outliving their prosthesis, and consideration must be given to how we are to provide the necessary capacity to meet the rising demand for revision surgery and how to maximise patient outcomes.

The purpose of this review was to examine the epidemiology of, and risk factors for, revision knee arthroplasty, and to discuss factors that may enhance patient outcomes.

Cite this article: Bone Joint J 2015; 97-B:723–8.


Bone & Joint Research
Vol. 4, Issue 6 | Pages 99 - 104
1 Jun 2015
Savaridas T Wallace RJ Dawson S Simpson AHRW

Objectives

There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed.

Methods

Skeletally mature aged rats were used. A total of 14 rats received 1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium chloride (control) daily. Stress at failure and toughness of the tibial diaphysis were calculated following four-point bending tests.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 64 - 70
1 Jan 2015
Hamilton DF Burnett R Patton JT Howie CR Moran M Simpson AHRW Gaston P

Total knee arthroplasty (TKA) is an established and successful procedure. However, the design of prostheses continues to be modified in an attempt to optimise the functional outcome of the patient.

The aim of this study was to determine if patient outcome after TKA was influenced by the design of the prosthesis used.

A total of 212 patients (mean age 69; 43 to 92; 131 female (62%), 81 male (32%)) were enrolled in a single centre double-blind trial and randomised to receive either a Kinemax (group 1) or a Triathlon (group 2) TKA.

Patients were assessed pre-operatively, at six weeks, six months, one year and three years after surgery. The outcome assessments used were the Oxford Knee Score; range of movement; pain numerical rating scales; lower limb power output; timed functional assessment battery and a satisfaction survey. Data were assessed incorporating change over all assessment time points, using repeated measures analysis of variance longitudinal mixed models. Implant group 2 showed a significantly greater range of movement (p = 0.009), greater lower limb power output (p = 0.026) and reduced report of ‘worst daily pain’ (p = 0.003) over the three years of follow-up. Differences in Oxford Knee Score (p = 0.09), report of ‘average daily pain’ (p = 0.57) and timed functional performance tasks (p = 0.23) did not reach statistical significance. Satisfaction with outcome was significantly better in group 2 (p = 0.001).

These results suggest that patient outcome after TKA can be influenced by the prosthesis used.

Cite this article: Bone Joint J 2015;97-B:64–70.


The Bone & Joint Journal
Vol. 96-B, Issue 11 | Pages 1566 - 1570
1 Nov 2014
Blackmur JP Tang EYH Dave J Simpson AHRW

We compared the use of broth culture medium for samples taken in theatre with the standard practice of placing tissue samples in universal containers. A total of 67 consecutive patients had standard multiple samples of deep tissue harvested at surgery and distributed equally in theatre either to standard universal containers or to broth culture medium. These samples were cultured by direct and enrichment methods. The addition of broth in theatre to standard practice led to an increase in sensitivity from 83% to 95% and an increase in negative predictive value from 77% to 91%. Placing tissue samples directly into broth in the operating theatre is a simple, inexpensive way to increase the sensitivity of cultures from infected patients, and does not appear to compromise the specificity of these cultures.

Cite this article: Bone Joint J 2014;96-B:1566–70.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1339 - 1343
1 Oct 2014
Hamilton DF Burnett R Patton JT Howie CR Simpson AHRW

Instability is the reason for revision of a primary total knee replacement (TKR) in 20% of patients. To date, the diagnosis of instability has been based on the patient’s symptoms and a subjective clinical assessment. We assessed whether a measured standardised forced leg extension could be used to quantify instability.

A total of 25 patients (11 male/14 female, mean age 70 years; 49 to 85) who were to undergo a revision TKR for instability of a primary implant were assessed with a Nottingham rig pre-operatively and then at six and 26 weeks post-operatively. Output was quantified (in revolutions per minute (rpm)) by accelerating a stationary flywheel. A control group of 183 patients (71 male/112 female, mean age 69 years) who had undergone primary TKR were evaluated for comparison.

Pre-operatively, all 25 patients with instability exhibited a distinctive pattern of reduction in ‘mid-push’ speed. The mean reduction was 55 rpm (sd 33.2). Post-operatively, no patient exhibited this pattern and the reduction in ‘mid-push’ speed was 0 rpm. The change between pre- and post-operative assessment was significant (p < 0.001). No patients in the control group exhibited this pattern at any of the intervals assessed. The between-groups difference was also significant (p < 0.001). This suggests that a quantitative diagnostic test to assess the unstable primary TKR could be developed.

Cite this article: Bone Joint J 2014;96-B:1339–43.


The Bone & Joint Journal
Vol. 96-B, Issue 5 | Pages 622 - 628
1 May 2014
Hamilton DF Lane JV Gaston P Patton JT MacDonald DJ Simpson AHRW Howie CR

Satisfaction with care is important to both patients and to those who pay for it. The Net Promoter Score (NPS), widely used in the service industries, has been introduced into the NHS as the ‘friends and family test’; an overarching measure of patient satisfaction. It assesses the likelihood of the patient recommending the healthcare received to another, and is seen as a discriminator of healthcare performance. We prospectively assessed 6186 individuals undergoing primary lower limb joint replacement at a single university hospital to determine the Net Promoter Score for joint replacements and to evaluate which factors contributed to the response.

Achieving pain relief (odds ratio (OR) 2.13, confidence interval (CI) 1.83 to 2.49), the meeting of pre-operative expectation (OR 2.57, CI 2.24 to 2.97), and the hospital experience (OR 2.33, CI 2.03 to 2.68) are the domains that explain whether a patient would recommend joint replacement services. These three factors, combined with the type of surgery undertaken (OR 2.31, CI 1.68 to 3.17), drove a predictive model that was able to explain 95% of the variation in the patient’s recommendation response. Though intuitively similar, this ‘recommendation’ metric was found to be materially different to satisfaction responses. The difference between THR (NPS 71) and TKR (NPS 49) suggests that no overarching score for a department should be used without an adjustment for case mix. However, the Net Promoter Score does measure a further important dimension to our existing metrics: the patient experience of healthcare delivery.

Cite this article: Bone Joint J 2014;96-B:622–8.


The Bone & Joint Journal
Vol. 95-B, Issue 12 | Pages 1632 - 1639
1 Dec 2013
Clement ND MacDonald D Simpson AHRW Burnett R

This study assessed the effect of concomitant back pain on the Oxford knee score (OKS), Short-Form (SF)-12 and patient satisfaction after total knee replacement (TKR). It involved a prospectively compiled database of demographics and outcome scores for 2392 patients undergoing primary TKR, of whom 829 patients (35%) reported back pain. Compared with those patients without back pain, those with back pain were more likely to be female (odds ratio (OR) 1.5 (95% confidence interval (CI) 1.3 to 1.8)), have a greater level of comorbidity, a worse pre-operative OKS (2.3 points (95% CI 1.7 to 3.0)) and worse SF-12 physical (2.0 points (95% CI 1.4 to 2.6)) and mental (3.3 points (95% CI 2.3 to 4.3)) components.

One year post-operatively, those with back pain had significantly worse outcome scores than those without with a mean difference in the OKS of 5 points (95% CI 3.8 to 5.4), in the SF-12 physical component of 6 points (95% CI 5.4 to 7.1) and in the mental component of 4 points (95% CI 3.1 to 4.9). Patients with back pain were less likely to be satisfied (OR 0.62, 95% CI 0.5 to 0.78).

After adjusting for confounding variables, concomitant back pain was an independent predictor of a worse post-operative OKS, and of dissatisfaction. Clinicians should be aware that patients suffering concomitant back pain pre-operatively are at an increased risk of being dissatisfied post-operatively.

Cite this article: Bone Joint J 2013;95-B:1632–9.


The Bone & Joint Journal
Vol. 95-B, Issue 9 | Pages 1263 - 1268
1 Sep 2013
Savaridas T Wallace RJ Salter DM Simpson AHRW

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm-2 (sd 7.63) vs 24.65 Nmm-2 (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Cite this article: Bone Joint J 2013;95-B:1263–8.


Bone & Joint Research
Vol. 2, Issue 5 | Pages 79 - 83
1 May 2013
Goffin JM Pankaj P Simpson AHRW Seil R Gerich TG

Objectives

Because of the contradictory body of evidence related to the potential benefits of helical blades in trochanteric fracture fixation, we studied the effect of bone compaction resulting from the insertion of a proximal femoral nail anti-rotation (PFNA).

Methods

We developed a subject-specific computational model of a trochanteric fracture (31-A2 in the AO classification) with lack of medial support and varied the bone density to account for variability in bone properties among hip fracture patients.


Bone & Joint Research
Vol. 2, Issue 4 | Pages 70 - 78
1 Apr 2013
Hamilton DF McLeish JA Gaston P Simpson AHRW

Objectives

Lower limb muscle power is thought to influence outcome following total knee replacement (TKR). Post-operative deficits in muscle strength are commonly reported, although not explained. We hypothesised that post-operative recovery of lower limb muscle power would be influenced by the number of satellite cells in the quadriceps muscle at time of surgery.

Methods

Biopsies were obtained from 29 patients undergoing TKR. Power output was assessed pre-operatively and at six and 26 weeks post-operatively with a Leg Extensor Power Rig and data were scaled for body weight. Satellite cell content was assessed in two separate analyses, the first cohort (n = 18) using immunohistochemistry and the second (n = 11) by a new quantitative polymerase chain reaction (q-PCR) protocol for Pax-7 (generic satellite cell marker) and Neural Cell Adhesion Molecule (NCAM; marker of activated cells).


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 11 | Pages 1506 - 1510
1 Nov 2012
Hamilton DF Gaston P Simpson AHRW

The aim of this study was to determine the association between the Oxford knee score (OKS) and direct assessment of outcome, and to examine how this relationship varied at different time-points following total knee replacement (TKR). Prospective data consisting of the OKS, numerical rating scales for ‘worst pain’ and ‘perceived mean daily pain’, timed functional assessments (chair rising, stairs and walking ability), goniometry and lower limb power were recorded for 183 patients pre-operatively and at six, 26 and 52 weeks post-operatively. The OKS was influenced primarily by the patient’s level of pain rather than objective functional assessments. The relationship between report of outcome and direct assessment changed over time: R2 = 35% pre-operatively, 44% at six weeks, 57% at 26 weeks and 62% at 52 weeks.

The relationship between assessment of performance and report of performance improved as the patient’s report of pain diminished, suggesting that patients’ reporting of functional outcome after TKR is influenced more by their pain level than their ability to accomplish tasks.


Bone & Joint Research
Vol. 1, Issue 11 | Pages 289 - 296
1 Nov 2012
Savaridas T Wallace RJ Muir AY Salter DM Simpson AHRW

Objectives

Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing.

Methods

A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1288 - 1291
1 Sep 2012
Sanghrajka AP Hill RA Murnaghan CF Simpson AHRW Bellemore MC

We describe three cases of infantile tibia vara resulting from an atraumatic slip of the proximal tibial epiphysis upon the metaphysis. There appears to be an association between this condition and severe obesity. Radiologically, the condition is characterised by a dome-shaped metaphysis, an open growth plate and disruption of the continuity between the lateral borders of the epiphysis and metaphysis, with inferomedial translation of the proximal tibial epiphysis. All patients were treated by realignment of the proximal tibia by distraction osteogenesis with an external circulator fixator, and it is suggested that this is the optimal method for correction of this complex deformity. There are differences in the radiological features and management between conventional infantile Blount’s disease and this ‘slipped upper tibial epiphysis’ variant.


Bone & Joint Research
Vol. 1, Issue 7 | Pages 152 - 157
1 Jul 2012
Hamilton DF Gatherer D Jenkins PJ Maclean JGB Hutchison JD Nutton RW Simpson AHRW

Objectives

To evaluate the neck strength of school-aged rugby players, and to define the relationship with proxy physical measures with a view to predicting neck strength.

Methods

Cross-sectional cohort study involving 382 rugby playing schoolchildren at three Scottish schools (all male, aged between 12 and 18 years). Outcome measures included maximal isometric neck extension, weight, height, grip strength, cervical range of movement and neck circumference.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 865 - 874
1 Jul 2012
Mills LA Simpson AHRW

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 277 - 284
1 Feb 2011
Amin AK Huntley JS Patton JT Brenkel IJ Simpson AHRW Hall AC

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury.

Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline.

These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 691 - 699
1 May 2009
Amin AK Huntley JS Simpson AHRW Hall AC

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture.

The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 12 | Pages 1553 - 1560
1 Dec 2007
Gaston MS Simpson AHRW

This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 565 - 566
1 May 2007
Simpson AHRW Dave J Cookson B


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 6 | Pages 701 - 705
1 Jun 2006
Simpson AHRW Mills L Noble B


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 107 - 110
1 Jan 2006
Watts AC Howie CR Simpson AHRW

The risk of venous thromboembolism in patients following arthroplasty may be reduced by continuing chemical thromboprophylaxis for up to 35 days post-operatively. This prospective cohort study investigated the compliance of 40 consecutive consenting patients undergoing lower limb arthroplasty with self-administration of a recommended subcutaneous chemotherapeutic agent for six weeks after surgery. Compliance was assessed by examination of the patient for signs of injection, number of syringes used, and a self-report diary at the end of the six-week period. A total of 40 patients, 15 men and 25 women, were recruited. One woman was excluded because immediate post-operative complications prevented her participation. Self-administration was considered feasible in 87% of patients (95% confidence interval (CI) 76 to 98) at the time of discharge. Among this group of 34 patients, 29 (85%) were compliant (95% CI 73 to 97). Patients can learn to self-administer subcutaneous injections of thromboprophylaxis, and compliance with extended prophylaxis to six weeks is good.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 583 - 587
1 Apr 2005
Szöke G Lee S Simpson AHRW Prescott J

Little is known about the increase in length of tendons in postnatal life or of their response to limb lengthening procedures. A study was carried out in ten young and nine adult rabbits in which the tibia was lengthened by 20% at two rates 0.8 mm/day and 1.6 mm/day.

The tendon of the flexor digitorum longus (FDL) muscle showed a significant increase in length in response to lengthening of the tibia. The young rabbits exhibited a significantly higher increase in length in the FDL tendon compared with the adults. There was no difference in the amount of lengthening of the FDL tendon at the different rates. Of the increase in length which occurred, 77% was in the proximal half of the tendon.

This investigation demonstrated that tendons have the ability to lengthen during limb distraction. This occurred to a greater extent in the young who showed a higher proliferative response, suggesting that there may be less need for formal tendon lengthening in young children.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 142 - 150
1 Feb 2005
Keating JF Simpson AHRW Robinson CM


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 8 | Pages 1182 - 1186
1 Nov 2004
Barker KL Simpson AHRW

This prospective, longitudinal study documents the muscle strength and baseline function of 18 patients undergoing closed femoral shortening for discrepancy in limb length. Patients were studied for two years following surgery. Function was measured by a self-reported questionnaire, timed tests of performance and measurements of muscle strength and power. After two years, the self-reported function and ability to complete timed functional tests had returned to or improved on the pre-operative values. Muscle strength remained slightly below the pre-operative value and was more marked in the quadriceps than the hamstrings. This study suggests that small decreases in muscle strength and power following closed femoral shortening do not adversely affect the patients’ ability to perform everyday activities.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 7 | Pages 1041 - 1046
1 Sep 2004
Porter DE Lonie L Fraser M Dobson-Stone C Porter JR Monaco AP Simpson AHRW

We performed a prospective genotype-phenotype study using molecular screening and clinical assessment to compare the severity of disease and the risk of sarcoma in 172 individuals (78 families) with hereditary multiple exostoses. We calculated the severity of disease including stature, number of exostoses, number of surgical procedures that were necessary, deformity and functional parameters and used molecular techniques to identify the genetic mutations in affected individuals. Each arm of the genotype-phenotype study was blind to the outcome of the other. Mutations EXT1 and EXT2 were almost equally common, and were identified in 83% of individuals. Non-parametric statistical tests were used.

There was a wide variation in the severity of disease. Children under ten years of age had fewer exostoses, consistent with the known age-related penetrance of this condition. The severity of the disease did not differ significantly with gender and was very variable within any given family. The sites of mutation affected the severity of disease with patients with EXT1 mutations having a significantly worse condition than those with EXT2 mutations in three of five parameters of severity (stature, deformity and functional parameters). A single sarcoma developed in an EXT2 mutation carrier, compared with seven in EXT1 mutation carriers. There was no evidence that sarcomas arose more commonly in families in whom the disease was more severe.

The sarcoma risk in EXT1 carriers is similar to the risk of breast cancer in an older population subjected to breast-screening, suggesting that a role for regular screening in patients with hereditary multiple exostoses is justifiable.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 81 - 85
1 Jan 2004
Barker KL Lamb SE Simpson AHRW

There are few reports on function after limb salvage surgery using the Ilizarov technique, and none that document the pattern of recovery or predict when maximum function returns. This prospective, longitudinal study documents the baseline functional abilities of 40 consecutive patients with nonunion of a fracture in the lower limb. Patients were studied for at least two and a half years following the completion of surgery. Function was measured by timed tests of functional performance and by the Toronto Extremity Salvage Score self-reported patient questionnaire.

Recovery was slowest in the early stages after removal of the frame and greatest between six months and one year. Statistically significant improvement continued up to, but not beyond two years. This observation has important implications for the length of follow-up incorporated into the rehabilitation programmes for patients, predictions of patient status in regard to compensation and for the design of future studies to evaluate functional outcome.


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 4 | Pages 604 - 610
1 May 2003
Reed AAC Joyner CJ Isefuku S Brownlow HC Simpson AHRW

Our aim was to develop a clinically relevant model of atrophic nonunion in the rat to test the hypothesis that the vessel density of atrophic nonunion reaches that of normal healing bone, but at a later time-point. Atrophic nonunion is usually attributed to impaired blood supply and is poorly understood.

We determined the number of blood vessels at the site of an osteotomy using immunolocalisation techniques in both normally healing bones and in atrophic nonunion. At one week after operation there were significantly fewer blood vessels in the nonunion group than in the healing group. By eight weeks, the number in the atrophic nonunion group had reached the same level as that in the healing group.

Our findings suggest that the number of blood vessels in atrophic nonunion reaches the same level as that in healing bone, but at a later time-point. Diminished vascularity within the first three weeks, but not at a later time-point, may prevent fractures from uniting.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 119 - 119
1 Feb 2003
Gaston P Perry C Abernethy PJ Emmanuel FX Simpson AHRW
Full Access

A knowledge of bacteriological profiles in previously treated cases is helpful as a guide to management of infected joint replacements, especially in those cases where bacteriology results are not available. The object of this study was to assess the changing trends of the bacteriology of infected total knee replacements (TKR) over 2 decades.

The records of 79 patients undergoing revision for infected TKR between 1979 and 1999 were reviewed. There were 30 males and 49 females, average age 63 years, range 36 – 82 years. The types and sensitivities of bacteria identified, and the use of prophylactic systematic and cement antibiotics, was recorded. The Chi-squared test was used to test statistical significance.

70 organisms were identified in 62 patients: 29 Staphylococcus aureus; 27 Coagulase Negative Staphylococci (CNS); 8 Streptococci; 6 Coliforms. In the 1980s S. aureus accounted for 55% of infections, CNS 25%. In the 1990s S. aureus 38%, CNS 41%. Following the use of systematic antibiotics (3 x cefuroxime) or antibiotic cement (bacitracin/erythromycin/colistin – BEC) at primary TKR, fewer CNS infections were seen (p< 0. 05). There was only 1 case of methicillin resistant S. aureus. Coagulase negative staphylococci had a 36% resistance to flucloxacillin. With BEC cement there was a tendency to increased erythromycin resistance in CNS, but this did not achieve statistical significance.

At revision for infected TKR, different bacterial profiles were observed depending on prophylactic antibiotic usage. As CNS now causes > 40% of infections, patients undergoing revision TKR should have antibiotics effective against CNS until definitive results are available.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 42 - 42
1 Jan 2003
Porter DE Fraser M Dobson-Stone C Monaco AM Simpson AHRW
Full Access

To determine whether the spectrum of genetic mutation in Hereditary Multiple Exostoses supports a neoplastic aetiology for this condition.

Historically, experts have been cautious in attributing neoplastic qualities to the osteochondroma. Solomon states ‘[osteochondromas] are not neoplastic in the ordinary sense of the word’; Morton that it ‘is not a tumour but a growth-aberration; Peterson that the ‘osteochondroma is not a true neoplasm’; and Schmale that ‘exostoses are the result of dysplasia of the lateral apect of the growth-plate’. There are, however, several features of osteochondroma behaviour common to other neoplasms which suggest a neoplastic aetiology:

the existence of an autosomal dominant inherited multiple form, in which lesions are histologically identical to the solitary form.

lesions which are distributed randomly and perhaps asymmetrically at ‘high-risk’ anatomical sites (usually adjacent to those physes with greatest growth potential).

evidence of behavioural or cellular disorder.

a potential for malignant transformation.

Recent genetic data has supported a fresh look at the neoplastic nature of osteochondromas. EXT1 and EXT2 genes are responsible for Hereditary Multiple Exostoses (HME). EXT1 codes for a protein which alters the synthesis and display of cell-surface heparan sulphate glycosaminoglycans; molecules which affect cellular growth, differentiation, motility and adhesion. Loss-of-function of such a gene may initiate a neoplastic pathogenesis in osteochondromas.

From 1996–1999, 51 families with HME were screened for EXT mutation, with mutations identified in 41 families. EXT mutation was assessed by means of fluorescent single-strand conformational polymorphism (f-SSCP) screening, followed by sequencing analysis.

Results : All missense mutations had previously been reported in the literature. In contrast, only 9 of 34 loss-of function mutations (frame-shift, splice-site and nonsense) had previously been reported.

All frame-shift, splice-site and nonsense mutations are loss-of-function. Missense mutations may result in partial or complete dysfunction if a crucial folding or binding site is involved. Since no missense mutations were new, this suggested their mutation sites are important, and may effectively result in loss-of-function. These data strongly support a tumour suppressor gene function for EXT genes, and a neoplastic pathogenesis for HME.