Objectives. Surgeons face a substantial risk of infection because of the occupational exposure to blood-borne pathogens (BBPs) from patients undergoing high-risk orthopaedic procedures. This study aimed to determine the seroprevalence of four BBPs among patients undergoing joint arthroplasty in Shanghai, China. In addition, we evaluated the significance of pre-operative screening by calculating a cost-to-benefit ratio. Methods. A retrospective observational study of pre-operative screening for BBPs, including hepatitis B and C viruses (HBV and HCV), human immunodeficiency virus (HIV) and Treponema pallidum (TP), was conducted for sequential patients in the orthopaedic department of a large urban teaching hospital between 01 January 2009 and 30 May 2016. Medical records were analysed to verify the seroprevalence of these BBPs among the patients stratified by age, gender, local origin, type of surgery, history of previous transfusion and marital status. Results. Of the subjects who underwent arthroplasty surgery in our institution, pre-operative screening tests were available for 96.1% (11 609 patients). The seroprevalence of HBV, HCV, HIV and TP was 5.47%, 0.45%, 0.08% and 3.6%, respectively. A total of 761 seropositive cases (68.4%) were previously undiagnosed. Pre-operative screening for HIV resulted in a low cost to benefit ratio, followed by HCV and HBV. Conclusion. Routine HCV and HIV screening prior to joint arthroplasty is not a cost-effective strategy. Considering the high rate of undiagnosed patients and the shortage of protective options, targeted pre-operative screening for HBV and syphilis should be considered for the protection of healthcare workers in China who have not been vaccinated. Cite this article: Bone Joint Res 2017;6:566–571

Objectives. We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change. Methods. We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1

Objectives. To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA). Methods. This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s t-tests were used for direct comparison, whilst segmented regression was employed for projection analysis. Results. There were statistically significant reductions in numbers of new patients seen face-to-face (140.4, . sd. 39.6 versus 461.6, . sd. 61.63, p < 0.0001), days to first orthopaedic review (5.2, . sd. 0.66 versus 10.9, . sd. 1.5, p < 0.0001), discharges (33.5, . sd. 3.66 versus 129.2, . sd. 7.36, p < 0.0001) and non-attendees (14.82, . sd. 1.48 versus 60.47, . sd. 2.68, p < 0.0001), in addition to a statistically significant increase in number of patients seen within 72-hours (46.4% 3873 of 8345 versus 5.1% 447 of 8771, p < 0.0001). There was a non-significant increase in consultation time of 1 minute 9 seconds (14 minutes 53 seconds . sd. 106 seconds versus 13 minutes 44 seconds . sd. 128 seconds, p = 0.0878). VFC saved the local CCG £67 385.67 in the first year and is set to save £129 885.67 annually thereafter. Conclusions. We have shown VFCs are clinically and cost-effective, with improvement across several clinical performance parameters and substantial financial savings for CCGs. To our knowledge this is the largest study addressing clinical practice implications of VFCs in England, using robust methodology to adjust for pre-existing trends. Further studies are required to appreciate whether our results are reproducible with local variations in the VFC model and payment tariffs. Cite this article: A. McKirdy, A. M. Imbuldeniya. The clinical and cost effectiveness of a virtual fracture clinic service: An interrupted time series analysis and before-and-after comparison. Bone Joint Res 2017;6:–269. DOI: 10.1302/2046-3758.65.BJR-2017-0330.R1

Objectives. This study reports on a secondary exploratory analysis of the early clinical outcomes of a randomised clinical trial comparing robotic arm-assisted unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis of the knee with manual UKA performed using traditional surgical jigs. This follows reporting of the primary outcomes of implant accuracy and gait analysis that showed significant advantages in the robotic arm-assisted group. Methods. A total of 139 patients were recruited from a single centre. Patients were randomised to receive either a manual UKA implanted with the aid of traditional surgical jigs, or a UKA implanted with the aid of a tactile guided robotic arm-assisted system. Outcome measures included the American Knee Society Score (AKSS), Oxford Knee Score (OKS), Forgotten Joint Score, Hospital Anxiety Depression Scale, University of California at Los Angeles (UCLA) activity scale, Short Form-12, Pain Catastrophising Scale, somatic disease (Primary Care Evaluation of Mental Disorders Score), Pain visual analogue scale, analgesic use, patient satisfaction, complications relating to surgery, 90-day pain diaries and the requirement for revision surgery. Results. From the first post-operative day through to week 8 post-operatively, the median pain scores for the robotic arm-assisted group were 55.4% lower than those observed in the manual surgery group (p = 0.040). At three months post-operatively, the robotic arm-assisted group had better AKSS (robotic median 164, interquartile range (IQR) 131 to 178, manual median 143, IQR 132 to 166), although no difference was noted with the OKS. At one year post-operatively, the observed differences with the AKSS had narrowed from a median of 21 points to a median of seven points (p = 0.106) (robotic median 171, IQR 153 to 179; manual median 164, IQR 144 to 182). No difference was observed with the OKS, and almost half of each group reached the ceiling limit of the score (OKS > 43). A greater proportion of patients receiving robotic arm-assisted surgery improved their UCLA activity score. Binary logistic regression modelling for dichotomised outcome scores predicted the key factors associated with achieving excellent outcome on the AKSS: a pre-operative activity level > 5 on the UCLA activity score and use of robotic-arm surgery. For the same regression modelling, factors associated with a poor outcome were manual surgery and pre-operative depression. Conclusion. Robotic arm-assisted surgery results in improved early pain scores and early function scores in some patient-reported outcomes measures, but no difference was observed at one year post-operatively. Although improved results favoured the robotic arm-assisted group in active patients (i.e. UCLA ⩾ 5), these do not withstand adjustment for multiple comparisons. Cite this article: M. J. G. Blyth, I. Anthony, P. Rowe, M. S. Banger, A. MacLean, B. Jones. Robotic arm-assisted versus conventional unicompartmental knee arthroplasty: Exploratory secondary analysis of a randomised controlled trial. Bone Joint Res 2017;6:631–639. DOI: 10.1302/2046-3758.611.BJR-2017-0060.R1

Objectives

Platelet-rich fibrin matrix (PRFM) has been proved to enhance tenocyte proliferation but has mixed results when used during rotator cuff repair. The optimal PRFM preparation protocol should be determined before clinical application. To screen the best PRFM to each individual’s tenocytes effectively, small-diameter culture wells should be used to increase variables. The gelling effect of PRFM will occur when small-diameter culture wells are used. A co-culture device should be designed to avoid this effect.

Objectives

The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known.

A complete cement mantle is important for the longevity of a total hip replacement. In the minimally-invasive direct anterior approach used at the Innsbruck University hospital, the femoral component has to be inserted into the femoral canal by an angulated movement. In a cadaver study, the quality and the extent of the cement mantle surrounding 13 Exeter femoral components implanted straight through a standard anterolateral transgluteal approach were compared with those of 13 similar femoral components implanted in an angulated fashion through a direct anterior approach. A third-generation cementing technique was used. The inner and outer contours of the cement mantles was traced from CT scans and the thickness and cross-sectional area determined. In no case was the cement mantle incomplete. The total mean thickness of the cement mantle was 3.62 mm (95% confidence interval 3.59 to 3.65). The mean thickness in the group using the minimally-invasive approach was 0.16 mm less than that in the anterolateral group. The distribution of the thickness was similar in the two groups. The mean thickness was less on the anteromedial and anterolateral aspect than on the posterior aspect of the femur. There is no evidence that the angulated introduction of Exeter femoral components in the direct anterior approach in cadavers compromises the quality, extent or thickness of the cement mantle

Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.

Aim

Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage.

Objectives

The patient-rated wrist evaluation (PRWE) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures (PROMs) used for clinical and research purposes. Methodological high-quality clinimetric studies that determine the measurement properties of these PROMs when used in patients with a distal radial fracture are lacking. This study aimed to validate the PRWE and DASH in Dutch patients with a displaced distal radial fracture (DRF).

Objectives

To explore whether orthopaedic surgeons have adopted the Proximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial results routinely into clinical practice.

Our aim was to analyse the influence of the size, shape and number of particles on the pathogenesis of osteolysis. We obtained peri-implant tissues from 18 patients having revision surgery for aseptically loosened Freeman total knee replacements (10), Charnley total hip replacements (3) and Imperial College/London Hospital double-cup surface hip replacements (5). The size and shape of the polyethylene particles were characterised using SEM and their concentration was calculated. The results were analysed with reference to the presence of radiological osteolysis. The concentration of polyethylene particles in 6 areas with osteolysis was significantly higher than that in 12 areas without osteolysis. There were no significant differences between the size and shape of the particles in these two groups. We conclude that the most critical factor in the pathogenesis of osteolysis is the concentration of polyethylene particles accumulated in the tissue

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Objectives

This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing.

Objectives

Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years.

Objectives

Adipose-derived mesenchymal stem cells (ADMSCs) are a promising strategy for orthopaedic applications, particularly in bone repair. Ex vivo expansion of ADMSCs is required to obtain sufficient cell numbers. Xenogenic supplements should be avoided in order to minimise the risk of infections and immunological reactions. Human platelet lysate and human plasma may be an excellent material source for ADMSC expansion. In the present study, use of blood products after their recommended transfusion date to prepare human platelet lysate (HPL) and human plasma (Hplasma) was evaluated for in vitro culture expansion and osteogenesis of ADMSCs.

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.

Objectives

We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model.

Objectives

All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors.

Objectives

Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH).

Objectives

Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.

Objectives

“Virtual fracture clinics” have been reported as a safe and effective alternative to the traditional fracture clinic. Robust protocols are used to identify cases that do not require further review, with the remainder triaged to the most appropriate subspecialist at the optimum time for review. The objective of this study was to perform a “top-down” analysis of the cost effectiveness of this virtual fracture clinic pathway.

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

Objectives

There are various pin-in-plaster methods for treating fractures of the distal radius. The purpose of this study is to introduce a modified technique of ‘pin in plaster’.

Objectives

Lengthening osteotomies of the calcaneus in children are in general grafted with bone from the iliac crest. Artificial bone grafts have been introduced, however, their structural and clinical durability has not been documented. Radiostereometric analysis (RSA) is a very accurate and precise method for measurements of rigid body movements including the evaluation of joint implant and fracture stability, however, RSA has not previously been used in clinical studies of calcaneal osteotomies. We assessed the precision of RSA as a measurement tool in a lateral calcaneal lengthening osteotomy (LCLO).

Objectives

The evidence base to inform the management of Achilles tendon rupture is sparse. The objectives of this research were to establish what current practice is in the United Kingdom and explore clinicians’ views on proposed further research in this area. This study was registered with the ISRCTN (ISRCTN68273773) as part of a larger programme of research.

High-intensity narrow-spectrum (HINS) light is a novel violet-blue light inactivation technology which kills bacteria through a photodynamic process, and has been shown to have bactericidal activity against a wide range of species. Specimens from patients with infected hip and knee arthroplasties were collected over a one-year period (1 May 2009 to 30 April 2010). A range of these microbial isolates were tested for sensitivity to HINS-light. During testing, suspensions of the pathogens were exposed to increasing doses of HINS-light (of 123mW/cm² irradiance). Non-light exposed control samples were also used. The samples were then plated onto agar plates and incubated at 37°C for 24 hours before enumeration. Complete inactivation (greater than 4-log₁₀ reduction) was achieved for all of the isolates. The typical inactivation curve showed a slow initial reaction followed by a rapid period of inactivation. The doses of HINS-light required ranged between 118 and 2214 J/cm². Gram-positive bacteria were generally found to be more susceptible than Gram-negative.

As HINS-light uses visible wavelengths, it can be safely used in the presence of patients and staff. This unique feature could lead to its possible use in the prevention of infection during surgery and post-operative dressing changes.

Cite this article: Bone Joint J 2015;97-B:283–8.

Objectives

Excessive acetabular coverage is the most common cause of pincer-type femoroacetabular impingement. To date, an association between acetabular over-coverage and genetic variations has not been studied. In this study we investigated the association between single nucleotide polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular coverage in Japanese individuals to identify a possible genetic variation associated with acetabular over-coverage.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

This protocol describes a pragmatic multicentre randomised controlled trial (RCT) to assess the clinical and cost effectiveness of arthroscopic and open surgery in the management of rotator cuff tears. This trial began in 2007 and was modified in 2010, with the removal of a non-operative arm due to high rates of early crossover to surgery.

Cite this article: Bone Joint Res 2014;3:155–60.

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.

Objectives

Our study aimed to examine not only the incidence but also the impact of noise from two types of total hip replacement articulations: ceramic-on-ceramic and ceramic-on-polyethylene.

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.

We have designed a prospective study to evaluate the usefulness of prolonged incubation of cultures from sonicated orthopaedic implants. During the study period 124 implants from 113 patients were processed (22 osteosynthetic implants, 46 hip prostheses, 54 knee prostheses, and two shoulder prostheses). Of these, 70 patients had clinical infection; 32 had received antibiotics at least seven days before removal of the implant. A total of 54 patients had sonicated samples that produced positive cultures (including four patients without infection). All of them were positive in the first seven days of incubation. No differences were found regarding previous antibiotic treatment when analysing colony counts or days of incubation in the case of a positive result. In our experience, extending incubation of the samples to 14 days does not add more positive results for sonicated orthopaedic implants (hip and knee prosthesis and osteosynthesis implants) compared with a conventional seven-day incubation period.

Cite this article: Bone Joint J 2013;95-B:1001–6.

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Objectives

We aimed to examine the characteristics of deep venous flow in the leg in a cast and the effects of a wearable neuromuscular stimulator (geko; FirstKind Ltd) and also to explore the participants’ tolerance of the stimulator.

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T₁, T₂ and T_1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative.

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant.

Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters.

These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders.

Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8⁺ lymphopenia) and 11 patients (13%) (CD3⁺ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8⁺ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

In an osteological collection of 3100 specimens, 70 were found with unilateral clavicular fractures which were matched with 70 randomly selected normal specimens. This formed the basis of a study of the incidence of arthritis of the acromioclavicular joint and the effect of clavicular fracture on the development of arthritis in the ipsilateral acromioclavicular joint. This was graded visually on a severity scale of 0 to 3. The incidence of moderate to severe arthritis of the acromioclavicular joint in normal specimens was 77% (100 specimens). In those with a clavicular fracture, 66 of 70 (94%) had arthritis of the acromioclavicular joint, compared to 63 of 70 (90%) on the non-injured contralateral side (p = 0.35).

Clavicles with shortening of 15 mm or less had no difference in the incidence of arthritis compared to those with shortening greater than 15 mm (p = 0.25). The location of the fracture had no effect on the development of arthritis.

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model.

The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count.

Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.

A retrospective series of 45 cases of chronic osteomyelitis collected over a period of 14 years was histologically classified into tuberculous osteomyelitis (25) and chronic non-granulomatous osteomyelitis (20). The tuberculous osteomyelitis group was divided into three subgroups: a) typical granulomas (13 cases); b) ill-defined granulomas (seven cases), and c) suspected granulomas (five cases). An in-house polymerase chain reaction amplifying the 245 bp nucleotide sequence, and capable of detecting 10 fg of DNA of Mycobacterium tuberculosis, was used on the DNA extracted from the paraffin blocks. The polymerase chain reaction was positive in 72% of cases (18) of tuberculous osteomyelitis, but when typical cases of tuberculous osteomyelitis with confirmed granulomas were considered (13), this increased to 84.6% (11). The chronic non-granulomatous osteomyelitis group gave positive polymerase chain reaction results in 20% of the cases (4).

Our preliminary study on tuberculous osteomyelitis shows that the polymerase chain reaction can be a very useful diagnostic tool, since a good correlation was seen between typical granulomas and polymerase chain reaction with a sensitivity of 84.6% and a specificity of 80%. In addition, our study shows that tuberculous osteomyelitis can be diagnosed in formalin-fixed paraffin-embedded tissues in the absence of typical granulomas.

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score.

All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue.

At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001).

The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced.

Anatomical descriptions of the lateral retinaculum have been published, but the attachments, name or even existence of its tissue bands and layers are ill-defined. We have examined 35 specimens of the knee. The deep fascia is the most superficial layer and the joint capsule is the deepest. The intermediate layer is the most substantial and consists of derivatives of the iliotibial band and the quadriceps aponeurosis. The longitudinal fibres of the iliotibial band merge with those of the quadriceps aponeurosis adjacent to the patella. These longitudinal fibres are reinforced by superficial arciform fibres and on the deep aspect by transverse fibres of the iliotibial band. The latter are dense and provide attachment of the iliotibial band to the patella and the tendon of vastus lateralis obliquus.

Our study identifies two important new findings which are a constant connection of the deep fascia to the quadriceps tendon superior and lateral to the patella, and, a connection of the deeper transverse fibres to the tendon of vastus lateralis obliquus.

External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7).

Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used.

Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group.

RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming.

In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open.

In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.

We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N vs 81 N; bone volume density 19% vs 20%). Treatment with PTH for two weeks followed by pamidronate almost doubled the pull-out force (152 N; p < 0.001) and the bone volume density (37%; ANOVA, p < 0.001). Pamidronate alone did not have this effect (89 N and 25%, respectively). Thus, the deterioration can be blocked by bisphosphonates. The clinical implications are discussed.

Achieving deep flexion after total knee replacement remains a challenge. In this study we compared the soft-tissue tension and tibiofemoral force in a mobile-bearing posterior cruciate ligament-sacrificing total knee replacement, using equal flexion and extension gaps, and with the gaps increased by 2 mm each. The tests were conducted during passive movement in five cadaver knees, and measurements of strain were made simultaneously in the collateral ligaments. The tibiofemoral force was measured using a customised mini-force plate in the tibial tray. Measurements of collateral ligament strain were not very sensitive to changes in the gap ratio, but tibiofemoral force measurements were. Tibiofemoral force was decreased by a mean of 40% (sd 10.7) after 90° of knee flexion when the flexion gap was increased by 2 mm. Increasing the extension gap by 2 mm affected the force only in full extension. Because increasing the range of flexion after total knee replacement beyond 110° is a widely-held goal, small increases in the flexion gap warrant further investigation.

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.

Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1⁺) and stem cell factor receptor, CD117 (c-kit⁺) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1⁺ mononuclear cell (MNC^sca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC^{sca-1+,c-kit+} counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.

Sca-1⁺ mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.

Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage.

Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test.

Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02).

We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue.

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis.

We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10⁷ AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10⁷ naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats.

Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month.

The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.

Clinical experience indicates the beneficial effects of antibiotic-loaded bone cement. Although in vitro studies have shown the formation of a biofilm on its surface they have not considered the gap between the cement and the bone. We have investigated bacterial survival in that gap. Samples with gaps 200 μm wide were made of different bone cements. These were stored dry (‘pre-elution’) or submersed in phosphate-buffered saline to simulate the initial release of gentamicin (‘post-elution’). The gaps were subsequently inoculated with bacteria, which had been isolated from infected orthopaedic prostheses and assessed for their sensitivity to gentamicin. Bacterial survival was measured 24 hours after inoculation. All the strains survived in plain cements. In the pre-elution gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115, survived, but in post-elution samples more strains did so, depending on the cement tested. Although high concentrations of gentamicin were demonstrated in the gaps only the gentamicin-sensitive strains were killed. This could explain the increased prevalence of gentamicin-resistant infections which are seen clinically.

Strains applied to bone can stimulate its development and adaptation. High strains and rates of strain are thought to be osteogenic, but the specific dose response relationship is not known. In vivo human strain measurements have been performed in the tibia to try to identify optimal bone strengthening exercises for this bone, but no measurements have been performed in the distal radial metaphysis, the most frequent site of osteoporotic fractures. Using a strain gauged bone staple, in vivo dorsal metaphyseal radial strains and rates of strain were measured in ten female patients during activities of daily living, standard exercises and falls on extended hands. Push-ups and falling resulted in the largest compression strains (median 1345 to 3146 με, equivalent to a 0.1345% to 0.3146% length change) and falling exercises in the largest strain rates (18 582 to 45 954 με/s). On the basis of their high strain and/or strain rates these or variations of these exercises may be appropriate for distal radial metaphyseal bone strengthening.