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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 44 - 44
1 Aug 2013
Frame MC Jones B
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Many orthopaedic procedures require implants to be trialled before definitive implantation. Where this is required, the trials are provided in a set with the instrumentation. The most common scenario this is seen in during elective joint replacements. In Scotland (2007) the Scottish Executive (http://www.sehd.scot.nhs.uk/cmo/CMO(2006)13.pdf) recommended and implemented individually packed orthopaedic implants for all orthopaedic sets. The premise for this was to reduce the risk of CJD contamination and fatigue of implants due to constant reprocessing from corrosion. During many trauma procedures determining the correct length of plate or size of implant can be challenging. Trials of trauma implants is no longer common place. Many implants are stored in closed and sealed boxes, preventing the surgeon looking at the implant prior to opening and contaminating the device. As a result many implants are incorrectly opened and either need reprocessed or destroyed due to infection control policy, thus implicating a cost to the NHS. With even the simplest implants costing several hundreds of pounds, this cost is a very significant waste in resources that could be deployed else where. My project was to develop a method to produce in department accurate, cheap and disposable trials for implants often used in trauma, where the original manufacturer do not offer the option of a trial off the shelf. The process had to not involve contaminating or destroying the original implant in the production of a trial.

Several implants which are commonly used within Glasgow Royal Infirmary and do not have trials were identified. These implants were then CT scanned within their sealed and sterile packaging without contamination. Digital 3D surface renders of the models were created using free open source software (OsiriX, MeshLab, NetFabb). These models were then processed in to a suitable format for 3D printing using laser sintering via a cloud 3D printing bureau (Shapeways.com). The implants were produced in polyamide PA220 material or in 316L stainless steel. These materials could be serialized using gamma irradiation or ethylene oxide gas. The steel models were suitable for autoclaving in the local CSSU.

The implants produced were accurate facsimiles of the original implant with dimensions within 0.7mm. The implants were cost effective, an example being a rim mesh was reproduced in polyamide PA220 plastic for £3.50 and in 316L stainless steel for £15. The models were produced within 10 days of scanning. The stainless steel trials were durable and suitable for reprocessing and resterilisation.

The production of durable, low cost and functional implant trials all completed in department was successful. The cost of production of each implant is so low that it would be offset if just one incorrect implant was opened during a single procedure. With some of the implants tested, the trials would have paid for themselves 100 times. This is a simple and cost saving technique that would help reduce department funding and aid patient care.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 51 - 51
1 Aug 2013
Robinson P Anthony I Stark A Jones B Ingram R
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The link between squeaking and ceramic on ceramic (CoC) bearings has been widely reported in orthopaedic literature and is described as a hard bearing phenomenon. We aim to look at the incidence of noise in CoC bearings compared to Metal on Polyethylene (MoP) bearing, which have yet to be linked to squeaking.

We developed a noise characterizing hip questionnaire and sent that along with the Oxford Hip Score (OHS) to 1000 patients; 3:2 ratio of CoC to MoP. 282 CoC patients and 227 MoP patients returned the questions: 509 patients in total. Our patient database provided details on femoral head size and the acetabular inclination angle, for each respondent

47 (17%) of the CoC hip patients reported noise compared to 19 (8%) of the MoP hip patients (P=0.054). 9 CoC patients and 4 MoP patients reported squeaking, while clicking was the most frequent answer in both groups. 27% patients with noise reported avoiding recreational activities because of it. Patient's with noisy hips scored on average, 5 points worse in the OHS (CoC: P = 0.04 and MoP: P = 0.007) and were on average 5 years younger (CoC: P<0.001 and MoP: P=0.007). No correlation was found between noisy hips and femoral head size or inclination angle.

The squeaking hip phenomenon is not exclusive to hard bearing THA. Noise from patient's hips may have social implications and this should be highlighted when consenting a patient for either of these hip procedures. In both implants, we showed there to be a correlation between noise production and a lower OHS. However, longer follow up studies are needed to link noise to a poorly functioning implant


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 14 - 14
1 Aug 2013
Drury C Elias-Jones C Tait G
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Arthritis of the glenohumeral joint accompanied by an irreparable tear of the rotator cuff can cause severe pain, disability and loss of function, particularly in the elderly population. Anatomical shoulder arthroplasty requires a functioning rotator cuff, however, reverse shoulder arthroplasty is capable of addressing both rotator cuff disorders and glenohumeral deficiencies. The Aequalis Reversed Shoulder Prosthesis design is based on two bio-mechanical principles by Grammont; a medialized center of rotation located inside the glenoid bone surface and second, a 155 degree angle of inclination. Combined, they increase the deltoid lever arm by distalizing the humerus and make the prosthesis inherently stable.

24 consecutive primary reverse total shoulder arthroplasties were performed by a single surgeon for arthritis with rotator cuff compromise and 1 as a revision for a failed primary total shoulder replacement between December 2009 and October 2012. Patients were assessed postoperatively with the use of the DASH score, Oxford shoulder score, range of shoulder motion and plain radiography with Sirveaux score for scapular notching.

Mean age at the time of surgery was 72.5 years (range 59 to 86). Average follow up time was 19.4 months (range 4 to 38). Functional outcome scores from our series were comparable with patients from other follow up studies of similar prosthesis design. All patients showed improvement in range of shoulder movement postoperatively. Complications included one dislocation, one acromion fracture and one humeral shaft fracture. No cases of deep infection were recorded. Overall, the short-term clinical results were promising for this series of patients and indicate reverse shoulder arthroplasty as an appropriate treatment for this group of patients.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 12 - 12
1 Aug 2013
Elias-Jones C MacLeod C
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In 2012 collagenase Clostridium histolyticum (Xiapex) was approved by the SMC for restricted use for the treatment of Dupuytren's contracture. Xiapex was approved on a case by case basis for patients with a palpable pretendinous cord, giving rise to MCPJ contracture of greater than 30 degrees. As of September 2012 we began to offer Xiapex injections to patients in Ayrshire who enquired about the injection, and met the SMC criteria.

To date injections have been performed on 3 patients, in a total of 7 digits. Patients were assessed prior to injection and manipulation, with the degree of contracture recorded and DASH scores noted. Each patient then underwent a standard injection of 0.58 mg of Xiapex. 48 hours post injection each patient underwent manipulation under local anaesthetic, with contractures remeasured, pain scored using a visual analogue scale and complications noted. Each patient was then reviewed at 4 weeks post injection where the residual degree of contracture was recorded and a further DASH score completed.

Mean contracture at the MCPJ prior to injection was 57° (range 34–80), and mean DASH score of 20.8 (range 16.7–24.2). Following manipulation mean residual contracture at the MCPJ measured 21° (range 18–28). The average pain score following was manipulation was rated at 1.1. Mild bruising and swelling were reported in all cases following injection, and manipulation resulted in 2 minor skin tears. At the 4 week review prolonged improvement of contracture was achieved with a mean residual contracture of 14° (range −2–40); with a significant improvement in DASH scores – mean 0.6 (range 0–1.8)

Despite small numbers, we have found Xiapex injections to be a successful and well tolerated treatment for moderate Dupuytren's disease. Further follow up is required to assess the longevity of the correction and ensure the cost effectiveness of Xiapex.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 14 - 14
1 Aug 2013
Joseph J Anthony I Jones B Blyth M
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The purpose of this study was to evaluate the effect of body mass index (BMI) on patients undergoing primary total knee arthroplasty for osteoarthritis. Data was collected on 664 patients at 4 centres all of whom received a Depuy PFC Sigma prosthesis. Data collected included patient demographics, Oxford Knee Score (OKS), American Knee Society Score, SF-12, complications of surgery and the need for revision.

14% of patients had a BMI<25, 35% were overweight (BMI-25–30), 32% suffered from Grade 1 obesity (BMI-30–35) and 19% had grade 2 obesity (BMI>35). Obese patients were more likely to be female, have a higher ASA grade, present at a younger age and do sedentary work or no work at all. Pre-operative Oxford knee score was significantly worse in the BMI>35 group (p<0.001).

After surgery there was a significant improvement in functional outcome measures at 5 years post-operatively with all BMI groups improved by an average of 18 or 19 points in the OKS. However because those patients with high BMI have poorer pre-operative Oxford scores their post-operative scores were lower compared to patients with a normal BMI. Similar findings were noted with range of motion of the knee joint.

Overall complication rates were found to be significantly higher in obese patients and both revision surgery and deep infection rates increased stepwise with increasing BMI levels.

Deep Infection rates were as follows: BMI<25 0%, BMI-25–30 1.3%, BMI-30–35 1.4%, BMI-35–40 3.2% and BMI>40 6.1%.

Revision rates were as follows: BMI<25 0%, BMI-25–30 0.9%, BMI-30–35 0.9%, BMI-35–40 3.2% and BMI>40 6.1%.

Although obese patients with knee osteoarthritis do benefit from joint arthroplasty, they suffer from an increased rate of complications and need for revision surgery.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 47 - 47
1 Aug 2013
Siddiqui M Bidaye A Baird E Jones B Stark A Abu-Rajab R Anthony I Ingram R
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We compared the postoperative wound discharge rates and 3 months clinical results of three types of wound closure and dressing – 2-octylcyanoacrylate with Opstie (G+O), 2-octylcyanoacrylate with Tegaderm (G+T), and Opsite without 2-octylcyanoacrylate (O) in patients having primary total hip arthroplasty.

We randomised 141 patients scheduled for primary total hip arthroplasty into 3 arms of this study- G+O, G+T, or O. The extent of wound discharge was recorded on a diagrammatic representation of the dressing in situ on paper and graded each day. Dressings were left in-situ provided the extent of wound discharge allowed for this. The patient was clinically reviewed at 3 months to assess their scar length, cosmesis, scar discomfort, and evidence of superficial or deep wound sepsis.

A greater number of patients dressings remained dry on day 1 postoperatively in the two groups with 2-octylcyanoacrylate compared to the no glue group p=0.001. G+T group had a significantly lower proportion of patients with increased leakage of wounds on 2nd postoperative day p=0.044. At 3 months review, there was no statistical difference in the Hollander score or scar discomfort.

In patients who have had primary total hip arthroplasty, usage of 2-octylcyanoacrylate for wound closure along with Tegaderm dressing reduces wound discharge. The same effect is not noted in glue with Opsite group. Whilst dressing changes required in the non-glue group compared from the two glue groups did not reach statistical significance, this may have clinical relevance for patients and nursing staff. No effect on postoperative length of stay, or wound complications was noted.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 20 - 20
1 Aug 2013
Elias-Jones C Reilly J Kerr S Meek R Patil S Kelly M Campton L McInnes I Millar N
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Femoroacetabular impingement (FAI) is a significant cause of osteoarthritis in young active individuals but the pathophysiology remains unclear. Increasing mechanistic studies point toward an inflammatory component in OA. This study aimed to characterise inflammatory cell subtypes in FAI by exploring the phenotype and quantification of inflammatory cells in FAI versus OA samples.

Ten samples of labrum were obtained from patients with FAI (confirmed pathology) during open osteochondroplasty or hip arthroscopy. Control samples of labrum were collected from five patients with osteoarthritis undergoing total hip arthroplasty. Labral biopsies were evaluated immunohistochemically by quantifying the presence of macrophages (CD68 and CD202), T cells (CD3), mast cells (mast cell tryptase) and vascular endothelium (CD34).

Labral biopsies obtained from patients with FAI exhibited significantly greater macrophage, mast cell and vascular endothelium expression compared to control samples. The most significant difference was noted in macrophage expression (p<0.01). Further sub typing of macrophages in FAI using CD202 tissue marker revealed and M2 phenotype suggesting that these cells are involved in a regenerate versus a degenerate process. There was a modest but significant correlation between mast cells and CD34 expression (r=0.4, p<0.05) in FAI samples.

We provide evidence for an inflammatory cell infiltrate in femoroacetabular impingement. In particular, we demonstrate significant infiltration of mast cells and macrophages suggesting a role for innate immune pathways in the events that mediate hip impingement. Further mechanistic studies to evaluate the net contribution and hence therapeutic utility of these cellular lineages and their downstream processes may reveal novel therapeutic approaches to the management of early hip impingement.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 16 - 16
1 Aug 2013
Kumar S O'Neill G Stark A Jones B McCartney P Wells J Ingram R
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The aim of this study was to characterise noise associated with ceramic-on-ceramic total hip arthroplasty (THA).

A questionnaire was constructed to assess noise associated with THA. 116 patients responded. All had ceramic-on-ceramic hybrid THA at Glasgow Royal Infirmary between 2005 and 2007 using a Trident prosthesis and Exeter stem. Oxford Hip Questionnaires (OHS) were also completed by the patients.

16.4% of respondents reported noise associated with their ceramic hip. The vast majority reported onset at least 1 year after implantation. The most common noise types were ‘clicking’ (47%) or ‘grinding’ (42%), while ‘squeaking’ was least frequently reported (11%). Noise was most commonly brought on by bending and during sit to stand movements.

No correlation was identified between the incidence of noise and any patient specific factor or demographic variable. The mean OHS at questionnaire follow-up was 39 and there was no significant difference in OHS when comparing noisy and silent hips (p=0.65). Only 1 patient limited social or recreational activities and overall patients felt the noise had minimal effect on their quality of life.

Acetabular component inclination angles were compared on post-operative x-rays. There was no significant difference (p=0.51) in inclination angles of the noisy (47.1°±6.3°, range 30–57°) and silent hips (47.8°±6.1°, range 35–68°). The groups were further analysed for deviation out with the desirable inclination range of 40–45°. Of the noisy hips, a total of 73% were out with this range compared to 63% in the silent hip group.

The incidence of noise within this ceramic-on-ceramic THA group did not appear to be related to patient specific factors, patient reported outcome (OHS) or acetabular inclination angles. Subjective appraisal of the noise revealed that ‘squeaking’ was not common but patients tended to report ‘clicking’ and ‘grinding’ more. The precipitation of noise with bending activities reinforces a possible mechanical cause.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 39 - 39
1 Aug 2013
Lavery J Anthony I Blyth M Jones B
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To validate the Modified Forgotten Joint Score (MFJS) as a new patient-reported outcome measure (PROM) in hip and knee arthroplasty against the UK's gold standard Oxford Hip and Knee Scores (OHS/OKS).

The original Forgotten Joint Score was created by Behrend et al to assess post-op hip/knee arthroplasty patients. It is a new assessment tool devised to provide a greater discriminatory power, particularly in the well performing patients. It measures an appealing concept; the ability of a patient to forget about their artificial joint in everyday life. The original FJS was a 12-item questionnaire, which we have modified to 10-items to improve reliability and missing data.

Postal questionnaires were sent out to 400 total hip/knee replacement (THR/TKR) patients who were 1–2 years post-op, along with the OHS/OKS and a visual pain analog score. The data collected from the 212 returned questionnaires (53% return rate) was analysed in relation to construct and content validity. A sub-cohort of 77 patients took part in a test-retest repeatability study to assess reliability of the MFJS.

The MFJS proved to have an increased discriminatory power in high-performing patients in comparison to the OHS and OKS, highlighted by its more normal frequency of distribution and reduced ceiling effects in the MFJS. 30.8% of patients (n=131) scored 42–48 (equivalent to 87.5–100 in the MFJS) or more in the OKS compared to just 7.69% in the MFJS TKR patients. The MFJS proved to have an increased test-retest repeatability based upon its intra-class correlation coefficient of 0.968 compared to the Oxford's 0.845.

The MFJS provides a more sensitive tool in the assessment of well performing hip and knee arthroplasties in comparison to the OHS/OKS. The MFJS tests the concept of awareness of a prosthetic joint, rather than pain and function and therefore should be used as adjunct to the OKS/OHS.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 17 - 17
1 Aug 2013
Boyle J Anthony I Jones B MacLean A Wheelwright E Blyth M
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A retrospective analysis was carried out to determine the influence of pre-existing spinal pathology on the outcome of Total Knee Replacement surgery. Data was collected from 345 patients who had undergone Total Knee Replacement, at four centres in the UK, between 2000 and 2007. Oxford Knee Scores (OKS), American Knee Society Scores (AKSS) and SF-12 questionnaires were recorded prospectively. Data was collected pre-operatively and then post-operatively at 3 months, 1 year and 2 years. Patients were divided into those with (n=40) and without a history of low back pain (n=305). In addition to determining the influence of low back pain on outcome after Total Knee Replacement we also examined the influence of concomitant hip and ankle pathology in the same cohort of patients.

OKS scores were significantly worse for patients with symptomatic low back pain at 3 (p=0.05), 12 (p=0.009) and 24 months (p=0.039) following surgery. SF-12 physical scores followed a comparable pattern with significance demonstrated at 3 (p=0.038), 12 (p=0.0002) and 24 months (p=0.016). AKSS followed a similar pattern, but significance was only reached at 1 year (p=0.013). The mental component of the SF-12 measure demonstrated a significant improvement in patients' mental health post-operatively for patients with no history of low back pain. In contrast patients with low back pain showed no improvement in mental health scores post-operatively.

In contrast to low back pain, hip and ankle pathology had no statistically significant detrimental effect on the outcome of Total Knee Replacement surgery.

This study demonstrates that low back pain significantly affects the functional outcome after Total Knee Replacement surgery and that patients with low back pain show no improvement in mental health post-operatively.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 53 - 53
1 Aug 2013
Jensen C Gupta S Sprowson A Chambers S Inman D Jones S Aradhyula N Reed M
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Currently, the cement being used for hemiarthroplasties and total hip replacements by the authors and many other surgeons in the UK is Palacos® (containing 0.5g Gentamicin). Similar cement, Copal® (containing 1g Gentamicin and 1g Clindamycin) has been used in revision arthroplasties, and has shown to be better at inhibiting bacterial growth and biofilm formation. We aim to investigate the effect on SSI rates of doubling the gentamicin dose and adding a second antibiotic (clindamycin) to the bone cement in hip hemiarthroplasty.

We randomised 848 consecutive patients undergoing cemented hip hemiarthroplasty for fractured NOF at one NHS trust (two sites) into two groups: Group I, 464 patients, received standard cement (Palacos®) and Group II, 384 patients, received high dose, double antibiotic-impregnated cement (Copal®). We calculated the SSI rate for each group at 30 days post-surgery. The patients, reviewers and statistician were blinded as to treatment group.

The demographics and co-morbid conditions (known to increase risk of infection) were statistically similar between the groups. The combined superficial and deep SSI rates were 5 % (20/394) and 1.7% (6/344) for groups I and II respectively (p=0.01). Group I had a deep infection rate 3.3 %(13/394) compared to 1.16% (4/344) in group II (p=0.082). Group I had a superficial infection rate 1.7 % (7/394) compared to 0.58% (2/344) in group II (p=0.1861). 33(4%) patients were lost to follow up, and 77 (9%) patients were deceased at the 30 day end point. There was no statistical difference in the 30 day mortality, C. difficile infection, or the renal failure rates between the two groups.

Using high dose double antibiotic-impregnated cement rather than standard low dose antibiotic-impregnated cement significantly reduced the SSI rate (1.7% vs 5%; p=0.01) after hip hemiarthroplasty for fractured neck of femur in this prospective randomised controlled trial.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 55 - 55
1 Aug 2013
Sciberras N Murphy E Jones B Blyth M
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Deep surgical infections are a serious complication of total knee arthroplasty (TKA). Various protocols exist for treating these infections, each with its own advocates. In this series we report the one to five year follow-up of infected TKA that were treated with a two-stage revision knee replacement at the Glasgow Royal Infirmary between December 2003 and March 2009.

48 patients were identified from the hospital database. 6 of these were excluded as they did not meet the stipulated infection criteria. Another patient was excluded as no notes were available thereby the infection status could not be determined. Another 8 patients were excluded as these only had a first stage.

33 patients (16 male) average age 67y (49–88) met the inclusion criteria. Mean BMI was of 31.62 (19–47) and 8 patients suffered from rheumatoid arthritis. At presentation, the median for the ESR, CRP and WCC were 70.5, 133 and 8.5 respectively. The infective organism was identified in 22 patients. Following the first stage, the patients were treated with antibiotics (initially intravenous followed by oral) for an average of 11.8 weeks (4–52 weeks). This procedure failed to eliminate the infection in 6 patients (18.18%) who had further re-admissions for infection of the affected prosthesis. The resultant success rate is of over 80% which is comparable to literature data (success rates of 41% to 96% quoted). For these patients, the average time to review was 25.13 months (12–67months). At review these patients had a mean extension of 2.17° (0–10°) and a mean flexion of 98.26 (70–120°). These patients were all satisfied with their outcome.

Our results show a high successful rate of elimination of infection when a two-stage revision is used for infected knee prosthesis with over 80% of patients free of infection.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_17 | Pages 27 - 27
1 Apr 2013
Owen SJ Roberts S Eisenstein S Jones P Sharp CA
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Background

Intervertebral disc cells exist in a challenging physiological environment. Disc degeneration occurs early in life implying that disc cells may no longer be able to maintain a functional tissue. We hypothesise that disc cells have a stress response different from most other cells because of the disc environment. We have compared the stress response of freshly isolated and cultured bovine nucleus pulposus (NP) cells with bovine dermal fibroblasts, representative of cells from a vascularised tissue.

Methods

Freshly isolated and passaged bovine NP cells and dermal fibroblasts were cultured for 3 days then subjected to either thermal stress at 45°C for 1h followed by recovery times of 6, 24 and 48h or nutrient stress involving culture without serum for 6, 24 and 48 h. At each time point, cell number and viability were assessed and heat shock protein 70 (Hsp70) measured in cell lysates by an enzyme-linked immunosorbent assay.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 73 - 73
1 Mar 2013
Bowers T Hodgson H Jones G Mustafa A Wilson C Williams R Fairhurst S Mason D
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Introduction

Total Knee Arthroplasty (TKA) aims to deliver relief from pain and restore normal function. Unfortunately, a significant cohort of patients report poor outcomes.

Hypothesis

Synovial fluid metabolite concentrations at surgery predict outcome of TKA, assessed by a validated measure.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 19 - 19
1 Mar 2013
Prys-Jones O Amin A Hall A
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The internal fixation of osteochondral fragments in fractures normally utilizes intra-articular screws inserted through a pilot hole drilled into cartilage/bone. This trauma causes cartilage injury leading to chondrocyte death. We have quantified the cell death following cartilage drilling and identified irrigation conditions that can protect chondrocytes. Articular cartilage of bovine metacarpophalangeal joints of 3yr-old cows was irrigated in the presence/absence of saline of various compositions. Holes were then made using a standard 1.5mm drill (Ortho Solutions Ltd.) at 18,000 rpm through the articular cartilage into bone. Osteochondral explants were then harvested and cultured in Dulbecco's Modified Eagle's Medium containing chloromethylfluorescein-di-acetate and propidium iodide (10uM each), to label living chondrocytes green and dead cells red, respectively. Axial images were taken by confocal microscopy and the width of the zone of cell death (ZCD) around the hole determined. With no irrigation, new drills caused a ZCD of 171±25um, which was increased when drills used 50+ times were tested (279±31um;p=0.03). With saline irrigation, the ZCD was reduced for old drills (150±6um;p=0.016) but not for new drills (124±8um) suggesting the heating effect of the old drills caused additional chondrocyte death. However for new drills, the ZCD was further reduced significantly to 82±7um when the osmolarity of the saline irrigation solution was raised to 480mOsm using sucrose. Data are mean±s.e.m., from at least 5 separate experiments each with a minimum of 3 replicates. The results demonstrate a chondroprotective effect of raising the osmolarity of saline used during drilling of cartilage which could be clinically beneficial.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 69 - 69
1 Aug 2012
Picardo N Nawaz Z Gallagher K Whittingham-Jones P Parratt T Briggs T Carrington R Skinner J Bentley G
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The aim of this study was to determine whether the clinical outcome of autologous chondrocyte transplantation was dependent on the timing of a high tibial osteotomy in tibio-femoral mal-aligned knees. Between 2000 and 2005, forty-eight patients underwent autologous chondrocyte implantation with HTO performed at varying times relative to the second stage autologous chondrocyte implantation procedure. 24 patients had HTO performed simultaneously with their second stage cartilage transplantation, (the HTO Simultaneous Group). 5 patients had HTO prior to their cartilage procedure, (the HTO pre-ACI Group) and 19 had HTO performed between 1 to 4 years after their second stage cartilage implantation, (the HTO post-ACI Group). There were 29 men and 19 women with a mean age of 37 years (Range 28 to 50) at the time of their second stage procedure.

With average follow-up of 72 months we have demonstrated a significant functional benefit in performing the HTO either prior to or simultaneously with the ACI procedure in the mal-aligned knee. The failure rate in the Post-ACI group was 45% compared to the Pre-ACI and Simultaneous group, with failure rates of 20% and 25%, respectively.

An HTO performed prior to or simultaneously with an autologous chondrocyte implantation procedure in the mal-aligned knee, provides a significant protective effect by reducing the failure rate by approximately 50%.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 7 - 7
1 Aug 2012
Smith J Dawson J Aarvold A Jones A Ridgway J Curran S Dunlop D Oreffo R
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Recent approaches have sought to harness the potential of stem cells to regenerate bone lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of skeletal stem cells (SSCs) for such applications, however previous studies have demonstrated that the concentration of SSCs present in iliac crest BMA is below that required for robust bone regeneration. Here we present a novel acoustic-facilitated filtration strategy to concentrate BMA for SSCs, clinically applicable for intra-operative orthopaedic use.

The aim of this study was to demonstrate the efficacy of this strategy in concentrating SSCs from iliac crest bone marrow, as well as femoral canal BMA from older patients.

Iliac crest BMA (Lonza, Rockville, MD, USA) and femoral canal BMA was obtained with informed consent from older patients during total hip replacement. 5 to 40ml of BMA was processed via the acoustically-aided exclusion filtration process to obtain 2-8 fold volume reductions. SSC concentration and function was assessed by flow-cytometry, assays for fibroblastic colony-forming units (CFU-F) and multi-lineage differentiation along chondrogenic, osteogenic and adipogenic pathways examined. Seeding efficiency of enriched and unprocessed BMA (normalised to cell number) onto allograft was assessed.

Iliac crest BMA from 15 patients was enriched for SSCs in a processing time of only 15 minutes. Femoral BMA from 15 patients in the elderly cohort was concentrated up to 5-fold with a corresponding enrichment of viable and functional SSCs, confirmed by flow cytometry and assays for CFU-F. Enhanced osteogenic (P<0.05) and chondrogenic (P<0.001) differentiation was observed using concentrated aspirate, as evidenced by biochemical assay and semi-quantitative histological analysis. Furthermore, enhanced cell seeding efficiency onto allograft was seen as an effect of SSC concentration per ml of aspirate (P<0.001), confirming the utility of this approach for application to bone regeneration.

The ability to rapidly enrich BMA demonstrates potential for intra-operative application to enhance bone healing and offers immediate capacity for clinical application to treat many scenarios associated with local bone stock loss. Further in vivo analysis is ongoing prior to clinical tests.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 117 - 117
1 Aug 2012
Aarvold A Smith J Tayton E Jones A Dawson J Briscoe A Lanham S Dunlop D Oreffo R
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Background

Skeletal stem cells can be combined with human allograft, and impacted to produce a mechanically stable living bone composite. This strategy has been used for the treatment of femoral head avascular necrosis, and has been translated to four patients, of which three remain asymptomatic at up to three year follow-up. In one patient collapse occurred in both hips due to widely distributed and advanced AVN disease, necessitating bilateral hip arthroplasty. However this has provided the opportunity to retrieve the femoral heads and analyse human tissue engineered bone.

Aims

Analysis of retrieved human tissue-engineered bone in conjunction with clinical follow-up of this translational case series.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 8 - 8
1 Aug 2012
Tan H Jones E Kozera L Henshaw K McGonagle D Giannoudis P
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Background and objectives

Fracture healing represents a physiological process regulated by a variety of signalling molecules, growth factors and osteogenic progenitor cells. Bone healing following trauma is associated with increased serum concentrations of several pro-inflammatory and angiogenic growth factors1. Platelet-derived growth factor (PDGF) has been shown to stimulate mesenchymal stem cell (MSC) proliferation in vitro. However, the in vivo relationship between the levels of PDGF and the numbers of MSCs in humans has not yet been explored. The aim of this study was to investigate PDGF release in the peripheral circulation following trauma and to correlate it with the numbers of MSCs in iliac crest bone marrow (BM) aspirate and in peripheral blood.

Methods

Trauma patients with lower extremity fractures (n=12, age 18-63 years) were recruited prospectively. Peripheral blood was obtained on admission, and at 1, 3, 5 and 7 days following admission. The serum was collected and PDGF was measured using the enzyme-linked immuno-sorbent assay (ELISA) technique. Iliac crest (BM) aspirate (20ml) and peripheral blood (PB) (20ml) was obtained on days 0-9 following admission. MSCs were enumerated using standard colony-forming unit fibroblasts (CFU-F) assay.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 116 - 116
1 Aug 2012
Theobald P Qureshi A Jones M
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Long bone fractures are a commonly presented paediatric injury. Whilst the possibility of either accidental or non-accidental aetiology ensures significant forensic relevance, there remain few clinical approaches that assist with this differential diagnosis. The aim of this current study was to generate a reproducible model of spiral fracture in immature bone, allowing investigation of the potential relationship between the rotational speed and the angle of the subsequent spiral fracture.

Seventy bovine metacarpal bones were harvested from 7 day old calves. Sharp dissection ensured removal of the soft tissue, whilst preserving the periosteum. The bones were then distributed evenly before eleven groups, before being aligned along their central axis within a torsional testing machine. Each group of bones were then tested to failure at a different rotational speed (0.5, 1, 15, 20, 30, 40, 45, 60, 75, 80 and 90 degrees s-1). The angle of spiral fracture, relative to the long axis, was then measured, whilst the fracture location, the extent of comminution and periosteal disruption, were all recorded.

Sixty-two out of 70 specimens failed in spiral fracture, with the remaining tests failing at the anchorage site. All bone fractures centred on the narrowest waist diameter, with 5 specimens (all tested at 90 degrees s-1) demonstrating comminution and periosteal disruption. The recorded spiral fracture angles ranged from 30 - 45 degrees, and were dependant on the rotational speed.

This study has established a relationship between the speed of rotation and the angle of spiral fracture in immature bovine bone. It is anticipated that further study will enable investigation of this trend in paediatric bone, ultimately providing an additional diagnostic tool for clinicians trying to verify the proposed mechanism of injury.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 74 - 74
1 Aug 2012
Mak J Moazen M Jones A Jin Z Tsirdis E Wilcox R
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Periprosthetic femoral fractures can occur as a complication of total hip arthroplasty and are often challenging to treat as the mechanical scenario is influenced by the presence of the metal prosthesis within the bone. This research focuses on finding the optimum fixation for transverse, Vancouver type B1 periprosthetic fractures, stabilised using locking plates and secured using screws. The aim of this study was to experimentally validate a computer model of a human femur, develop that model to represent a periprosthetic femoral fracture fixation and show how the model could be used to indicate differences between plating techniques.

In the first development stage, both a laboratory model and a finite element model were developed to evaluate the mechanical behaviour of an intact composite femur under axial loading. Axial strains were recorded along the medial length of the femur in both cases and compared to provide validation for the computational model predications. The computational intact femur model was then modified to include a cemented total hip replacement, and further adapted to include a periprosthetic fracture stabilised using a locking plate, with unicortical screws above, and bicortical screws below the transverse fracture.

For the intact femur case, the experimental and computational strain patterns correlated well with an average difference of 16%. Following the inclusion of the stem, there was a reduction in the strain in the region of the prosthesis reducing by an average of 45%. There was also a large increase in bulk stiffness with the introduction of the prosthesis. When the fracture and plate fixation were included, there was little difference in the proximal strain where the stem dominated, and the strains in the distal region were found to be highly sensitive to the distribution of the screws.

The results of this study indicate that screw configuration is an important factor in periprosthetic fracture fixation. A laboratory model of the periprosthetic facture case is now under development to further validate the computational models and the two approaches will then be used to determine optimum fixation methods for a range of clinical scenarios.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVIII | Pages 1 - 1
1 Jun 2012
Bell S Young P Drury C Jones B Blyth M MacLean A
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Total knee arthroplasty is an established and successful operation. In up to 13% of patients who undergo total knee arthroplasty continue to complain of pain. Recently computerised tomography (CT) has been used to assess the rotational profile of both the tibial and femoral components in painful total knee arthroplasty.

We reviewed 56 painful total knee replacements and compared these to 56 matched patients with pain free total knee replacements. Patients with infection, aseptic loosening, revision arthroplasties and gross coronal malalignment were excluded. Datum gathered from case notes and radiographs using a prospective orthopaedic database to identify patients. The age, sex, preoperative and postoperative Oxford scores, visual analogue scores and treatments recorded. The CT information recorded was limb alignment, tibial component rotation, femoral component rotation and combined rotation.

The two cohorts of patients had similar demographics. The mean limb alignments were 1.7 degrees varus and 0.01 degrees valgus in the painful and control groups respectively. A significant difference in tibial component rotation was identified between the groups with 3.2 degrees of internal rotation in the painful group compared to 0.5 degrees of external rotation in the control group (p=0.001). A significant difference in femoral component rotation was identified between the groups with 3.8 degrees of internal rotation in the painful group compared to 1.1 degrees of external rotation in the control group (p=0.001). A significant difference in the combined component rotation was identified between the groups with 6.8 degrees of internal rotation in the painful group compared to 1.7 degrees of external rotation in the control group (p=0.001).

We have identified significant internal rotation in a patient cohort with painful total knee arthroplasty when compared to a control group with internal rotation of the tibial component, femoral component and combined rotation. This is the largest comparison series currently in the literature.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 47 - 47
1 May 2012
Bottomley N McNally E Jones L Javaid M Arden N Gill H Dodd C Murray D Beard D Price A
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Introduction

Anteromedial osteoarthritis of the knee (anteromedial gonarthrosis-AMG) is a common form of knee arthritis. In a clinical setting, knee arthritis has always been assessed by plain radiography in conjunction with pain and function assessments. Whilst this is useful for surgical decision making in bone on bone arthritis, plain radiography gives no insight to the earlier stages of disease. In a recent study 82% of patients with painful arthritis had only partial thickness joint space loss on plain radiography. These patients are managed with various surgical treatments; injection, arthroscopy, osteotomy and arthroplasty with varying results. We believe these varying results are in part due to these patients being at different stages of disease, which will respond differently to different treatments. However radiography cannot delineate these stages. We describe the Magnetic Resonance Imaging (MRI) findings of this partial thickness AMG as a way of understanding these earlier stages of the disease.

Method

46 subjects with symptomatic partial thickness AMG underwent MRI assessment with dedicated 3 Tesla sequences. All joint compartments were scored for both partial and full thickness cartilage lesions, osteophytes and bone marrow lesions (BML). Both menisci were assessed for extrusion and tear. Anterior cruciate ligament (ACL) integrity was also assessed. Osteophytes were graded on a four point scale in the intercondylar notch and the lateral margins of the joint compartments. Scoring was performed by a consultant radiologist and clinical research fellow using a validated MRI atlas with consensus reached for disagreements. The results were tabulated and relationships of the interval data assessed with linear by linear Chi2 test and Pearson's Correlation.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 60 - 60
1 May 2012
McGonagle L Jones M Dowson D King P Theobald P
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Frictional resistance to tendon gliding is minimised by surrounding loose areolar tissues. During periods of prolonged immobilisation, for example post tendon-repair, adhesions can form between the two adjacent tissues, thereby limiting function. Whilst agents applied during surgery are recognised to succeed in adhesion prevention, they have also been reported to provide some reduction in friction during in vitro tendon-bony pulley investigations. This study investigated the effectiveness of common anti-adhesion agents in lubricating the tendon-surrounding tissue contact by comparison with a control study. By using a validated apparatus and with reference to the Stribeck curve, it was determined that the natural in vivo contact is likely to be lubricated by a film of synovial-like fluid. Application of all anti-adhesives generated a similarly efficient lubricating system, and hence administration of these agents should be encouraged to all regions of the tendon disrupted during surgery. Minimising frictional resistance to gliding will reduce the likelihood of tendon ‘gapping’ - and subsequently failure - at the repair site.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 26 - 26
1 May 2012
Jones A Aarvold A New A Dunlop D Oreffo R
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AIM

Avascular necrosis (AVN) of the femoral head is a potentially debilitating disease of the hip in young adults. Impaction bone grafting (IBG) of morcellised fresh frozen allograft is used in a number of orthopaedic conditions. This study has examined the potential of skeletal stem cells (SSC) to augment the mechanical properties of impacted bone graft and we translate these findings into clinical practice.

STUDY DESIGN

We have examined the effect of SSC density on augmentation of bone formation. An in vitro model was developed to replicate the surgical IBG process. Plain allograft was used as the control, and the SSC's seeded at a density of 5×103, 5×104 and 2×105 cells per cc of allograft for the experimental groups. All samples were cultured for 2 weeks and mechanically tested to determine shear strength using the Mohr Coulomb failure curve. The approach was translated to 3 patients with early avascular necrosis (AVN) of the femoral head. The patient's bone marrow was concentrated in theatre using a centrifugation device and the concentrated fraction of SSC's were seeded onto milled allograft. The patient's necrotic bone was drilled, curetted and replaced with impacted allograft seeded with SSC's. Osteogenic potential of concentrated and unconcentrated marrow was simultaneously compared in vitro by colony forming unit assays.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 35 - 35
1 May 2012
Cox G Giannoudis P Boxall S Buckley C Jones E McGonagle D
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Introduction

Iliac crest bone marrow aspirate (ICBMA) is frequently cited as the ‘gold-standard’ source of MSCs. MSCs have been shown to reside within the intramedullary (IM) cavities of long-bones [Nelea, 2005] however a comparative assessment with ICBMA has not yet been performed and the phenotype of the latter compartment MSCs remains undefined in their native environment.

Methods

Aspiration of the IM cavities of 6 patients' femurs with matched ICBMA was performed. The long-bone-fatty-bone-marrow (LBFBM) was filtered (70μm) to separate liquid and solid fractions and the solid fraction was briefly (60min, 37oC) digested with collagenase. MSC enumeration was performed using the colony-forming-unit-fibroblast (CFU-F) assay and quantification of cells with the CD45low CD271+ phenotype by flow-cytometry. [Jones 2002, Buhring 2007] MSCs were cultured and standard expansion media and passage 2 cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 80 - 80
1 May 2012
Thomas GER Simpson DJ Gill HS Glyn-Jones S Beard DJ Murray DW EPOS study group
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Femoral stem varus has been associated with poorer results. We report the incidence of varus/valgus malalignment of the Exeter polished, double taper design in a multicentre prospective study. The surgical outcomes at a minimum of five year and complication rates are also reported.

A multicentre prospective study of 987 total hip replacements was undertaken to investigate whether there is an association between surgical outcome and femoral stem malalignment. The primary outcome measure was the change in the Oxford hip score (OHS) at five years. Secondary outcomes included the rate of dislocation and revision.

The incidence of varus and valgus malignment were 7.1% and 2.6% respectively. There was no significant difference in OHS between neutral and malaligned femoral stems at 5 years (neutral, mean = 40.2; varus, mean 39.3, p = 0.465; valgus, mean = 40.9, p = 0.605). There was no significant difference in dislocation rate between the groups (p = 0.66). There was also no significant difference in revision rate (p = 0.34).

This study provides evidence that the Exeter stem is extremely tolerant of varus and valgus malalignment, both in terms of outcome and complication rate.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 82 - 82
1 May 2012
Jones A Hing K
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Background, Context and Motivation

“Increases in reconstructive orthopaedic surgery, resulting from advances in surgical practice and the ageing population, have lead to a demand for bone graft that far exceeds supply.”…Traditional bone grafting methods have been linked with a number of negative issues including increased morbidity due to secondary operation site and action as a vector for spread of disease. (Hing 2004). A solution to these insufficiencies would be the creation of a synthetic osteoinductive bone graft material. This would vastly improve bone graft surgery success rates and expedite post-op recovery times. The aim of this study was to classify then explore the dissolution rates of three experimental hydroxyapatite/silicate apatite synthetic bonegrafts in physiological solutions, (phosphate buffered saline, (PBS) +/− serum proteins, (PBS +FCS). The overall objective being to identify whether there is an explainable significant difference in ion exchange that could be behind the osteoinductive phenomena.

Methods Used

Classification of the apatite samples, (HA, SA1 and SA2), was conducted via X-Ray diffraction, FTIR-PAS Spectroscopy and SEM with EDS analysis. A dissolution experiment of the experimental apatites was conducted in PBS and PBS + FCS solutions, over time periods of 1, 2 and 4 hours, and at 1, 2, 4 and 8 days, with repeat measures.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 5 - 5
1 May 2012
Cox G McGonagle D Boxall S Buckley C Jones E Giannoudis P
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Introduction

Therapeutic exploitation of MSCs in orthopaedics has been tempered by their scarcity within ‘gold-standard’ iliac crest bone marrow aspirate (ICBMA) and the resulting need to expand cells in vitro. This is time-consuming, expensive and results in cells with a reduced differentiation capacity. [Banfi 2000] The RIA is a device that provides continuous irrigation and suction during reaming of long bones. Aspirated contents pass via a filter, trapping bony-fragments, before moving into a ‘waste’ bag, from which MSCs have been previously isolated. [Porter 2009] We hypothesised that ‘waste’ RIA bag contains more MSCs than a standard aspirated volume of ICBMA (30 ml). We further hypothesised than a fatty solid phase within this ‘waste bag’ contains many MSCs trapped within the adipocyte-rich stromal network and hence requiring an enzymatic digestion for their efficient release [Jones 2006].

Methods

The discarded filtrate ‘waste’ bag that contained saline from marrow cavity irrigation procedure from RIA reaming (7 patients) was filtered (70μm) and the solid fraction digested for 60min (37oC) with collagenase. MSC enumeration was performed using the colony-forming-unit-fibroblast (CFU-F). Following culture in standard expansion media, passage 2 cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages and their phenotype was assessed using flow cytometry. ICBMA from the same patients was used as controls.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 60 - 60
1 Mar 2012
Jones L Hungerford D
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Bone marrow is an environment rich in its diversity of cell types and niches. Both hematopoietic and osteogenic stromal cells are present and have been studied extensively. Less is known about the function of one of the most abundant cell types in the bone marrow: adipocytes. There are several hypotheses that have been proposed including: passive role as a space filler; active role in the body's general lipid metabolism; role in providing a localized energy reservoir for emergency situations affecting the bone or hematopoiesis; support of differentiation or function of other cell types (such as bone, endothelial, and other stromal cells).

There are several human pathologies associated with increases in adipocyte hypertrophy or proliferation including changes associated with aging, osteoporosis, and osteonecrosis. The reasons for these changes are poorly understood. One etiology associated with both osteoporosis and osteonecrosis, corticosteroid therapy, has been shown to increase the lipid content of osteoblasts and adipocytes.

With osteonecrosis, several pathogenetic mechanisms involving adipocytes have been proposed:

Mechanical - increased size and number cause increased intraosseous pressure and decreased venous outflow

Direct precursor cells away from osteoblastogenesis towards adipogenesis

Liquid fat causing a hypercoagulable state

Osteocyte dysfunction or apoptosis

Adipocyte and bone marrow necrosis

Release adipokines and other factors that have an effect on the cells within the bone marrow (inhibiting angiogenesis, e.g.)

The possibility that adipocytes may actually play an active role in propagating specific pathologic features has only recently been discussed. This is in part due to our increasing understanding that adipocytes have an endocrine role in metabolism.

Only recently have scientists tried to identify specific cellular mechanisms that may be involved in the pathogenesis of osteonecrosis. Results from these studies will not only contribute to our understanding of the disease of osteonecrosis (and other diseases such as osteoporosis) but will also help us to appreciate the multiple functionalities of the heretofore unappreciated adipocyte.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 2 | Pages 271 - 277
1 Feb 2009
Toms AD Barker RL McClelland D Chua L Spencer-Jones R Kuiper J

The treatment of bony defects of the tibia at the time of revision total knee replacement is controversial. The place of compacted morsellised bone graft is becoming established, particularly in contained defects. It has previously been shown that the initial stability of impaction-grafted trays in the contained defects is equivalent to that of an uncemented primary knee replacement. However, there is little biomechanical evidence on which to base a decision in the treatment of uncontained defects. We undertook a laboratory-based biomechanical study comparing three methods of graft containment in segmental medial tibial defects and compared them with the use of a modular metal augment to bypass the defect.

Using resin models of the proximal tibia with medial defects representing either 46% or 65% of the medial cortical rim, repair of the defect was accomplished using mesh, cement or a novel bag technique, after which impaction bone grafting was used to fill the contained defects and a tibial component was cemented in place. As a control, a cemented tibial component with modular metal augments was used in identical defects. All specimens were submitted to cyclical mechanical loading, during which cyclical and permanent tray displacement were determined.

The results showed satisfactory stability with all the techniques except the bone bag method. Using metal augments gave the highest initial stability, but obviously lacked any potential for bone restoration.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1298 - 1302
1 Sep 2005
Iesaka K Jaffe WL Jones CM Kummer FJ

We have investigated the role of the penetration of saline on the shear strength of the cement-stem interface for stems inserted at room temperature and those preheated to 37°C using a variety of commercial bone cements. Immersion in saline for two weeks at 37°C reduced interfacial strength by 56% to 88% after insertion at room temperature and by 28% to 49% after preheating of the stem. The reduction in porosity as a result of preheating ranged from 71% to 100%. Increased porosity correlated with a reduction in shear strength after immersion in saline (r = 0.839, p < 0.01) indicating that interfacial porosity may act as a fluid conduit.


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

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this.

We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks.

The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss.

Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines.