The identification of the extent of neural damage in patients with acute or chronic spinal cord injury is imperative for the accurate prediction of neurological recovery. The changes in signal intensity shown on routine MRI sequences are of limited value for predicting functional outcome. Diffusion tensor imaging (DTI) is a novel radiological imaging technique which has the potential to identify intact nerve fibre tracts, and has been used to image the brain for a variety of conditions. DTI imaging of the spinal cord is currently only a research tool, but preliminary studies have shown that it holds considerable promise in predicting the severity of spinal cord injury. . This paper briefly reviews our current knowledge of this technique

Aims. The aim of this study was to use diffusion tensor imaging (DTI) to investigate changes in diffusion metrics in patients with cervical spondylotic myelopathy (CSM) up to five years after decompressive surgery. We correlated these changes with clinical outcomes as scored by the Modified Japanese Orthopedic Association (mJOA) method, Neck Disability Index (NDI), and Visual Analogue Scale (VAS). Methods. We used multi-shot, high-resolution, diffusion tensor imaging (ms-DTI) in patients with cervical spondylotic myelopathy (CSM) to investigate the change in diffusion metrics and clinical outcomes up to five years after anterior cervical interbody discectomy and fusion (ACDF). High signal intensity was identified on T2-weighted imaging, along with DTI metrics such as fractional anisotropy (FA). MJOA, NDI, and VAS scores were also collected and compared at each follow-up point. Spearman correlations identified correspondence between FA and clinical outcome scores. Results. Significant differences in mJOA scores and FA values were found between preoperative and postoperative timepoints up to two years after surgery. FA at the level of maximum cord compression (MCL) preoperatively was significantly correlated with the preoperative mJOA score. FA postoperatively was also significantly correlated with the postoperative mJOA score. There was no statistical relationship between NDI and mJOA or VAS. Conclusion. ms-DTI can detect microstructural changes in affected cord segments and reflect functional improvement. Both FA values and mJOA scores showed maximum recovery two years after surgery. The DTI metrics are significantly associated with pre- and postoperative mJOA scores. DTI metrics are a more sensitive, timely, and quantifiable surrogate for evaluating patients with CSM and a potential quantifiable biomarker for spinal cord dysfunction. Cite this article: Bone Joint J 2020;102-B(9):1210–1218

Aims. The aim of this study was to evaluate the time course of changes in parameters of diffusion tensor imaging (DTI) such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in patients with symptomatic lumbar disc herniation. We also investigated the correlation between the severity of neurological symptoms and these parameters. . Patients and Methods. A total of 13 patients with unilateral radiculopathy due to herniation of a lumbar disc were investigated with DTI on a 1.5T MR scanner and underwent micro discectomy. There were nine men and four women, with a median age of 55.5 years (19 to 79). The changes in the mean FA and ADC values and the correlation between these changes and the severity of the neurological symptoms were investigated before and at six months after surgery. . Results. The mean FA values were significantly lower (p = 0.0005) and mean ADC values were significantly higher (p = 0.0115) in compressed nerves than in intact nerves. Although the FA values increased significantly at six months after surgical treatment (p = 0.020), the ADC values decreased but not significantly (p = 0.498). There were strong correlations between the DTI parameters such as the FA value and the severity of the neurological symptoms as assessed using the Japanese Orthopaedic Association (JOA) score and the Roland-Morris Disability Questionnaire (RDQ). . Conclusion. This preliminary study suggests that it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with lumbar nerve entrapment. Take home message: DTI is a potential tool for functional diagnosis of lumbar nerve damage. Cite this article: Bone Joint J 2016;98-B:387–94

The diffusion of Fucidin, gentamicin, and clindamycin from acrylic cement was tested in an in vitro system. The activity of Fucidin was very short-lived and only against gram-positive organisms; gentamicin inhibited gram-positive and gram-negative organisms for twenty-two and eleven days respectively; clindamycin had significant action only against gram-positive organisms and retained some activity for fifty-six days. We suggest that the destruction of organisms in the tissues is more likely to be achieved by topical and intravenous administration of antibiotics during the operation than by incorporation of antibiotic in the cement

We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

Objectives. Inflammation of the retrocalcaneal bursa (RB) is a common clinical problem, particularly in professional athletes. RB inflammation is often treated with corticosteroid injections however a number of reports suggest an increased risk of Achilles tendon (AT) rupture. The aim of this cadaveric study was to describe the anatomical connections of the RB and to investigate whether it is possible for fluid to move from the RB into AT tissue. Methods. A total of 20 fresh-frozen AT specimens were used. In ten specimens, ink was injected into the RB. The remaining ten specimens were split into two groups to be injected with radiological contrast medium into the RB either with or without ultrasonography guidance (USG). Results. In specimens injected with ink, diffusion outside the RB was observed with staining of the anterior portion of the AT. In eight contrast-injected specimens (five USG, three non-USG), a similar localised diffusion pattern was observed, with the contrast identified superiorly and anteriorly. In two contrast-injected specimens (non-USG), the diffusion pattern was more extensive. Conclusion. This study confirmed the existence of connections between the RB and the AT, especially rich in the anteroinferior portion of the tendon, which should be considered a weak zone for substances injected into the RB. We hypothesise that this part of the AT might be most vulnerable to rupture after corticosteroid injections. Cite this article: P. A. Pękala, B. M. Henry, J. R. Pękala, K. Piska, K. A. Tomaszewski. The Achilles tendon and the retrocalcaneal bursa: An anatomical and radiological study. Bone Joint Res 2017;6:446–451. DOI:10.1302/2046-3758.67.BJR-2016-0340.R1

Objectives. Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin. Methods. Vancomycin-impregnated articulating cement spacers and fosfomycin-impregnated articulating cement spacers were immersed in sterile phosphate-buffered saline (PBS) solutions and then incubated. Samples were collected for bioactivity evaluation. The aliquots were tested for MRSA inhibition with the disc diffusion method, and the inhibition zone diameters were measured. The inhibition zone differences were evaluated using the Wilcoxon Rank Sum Test. Results. The vancomycin group had significantly larger inhibition zones than the fosfomycin group from day three through to completion of the fourth week of incubation (p < 0.001). The vancomycin group exhibited a MRSA inhibition zone up to four weeks but the fosfomycin group showed an inhibition zone for only three days and after that did not show the the potential to inhibit MRSA. Conclusion. This in vitro study found that the inhibitory effect of vancomycin-impregnated articulating cement spacers against MRSA outperformed fosfomycin-impregnated articulating cement spacers. Further comparing our results to other published reports suggests there might be a limitation of the disc diffusion bioassay to show a large inhibitory zone in a high concentration of a highly soluble antibiotic. Cite this article: V. Yuenyongviwat, N. Ingviya, P. Pathaburee, B. Tangtrakulwanich. Inhibitory effects of vancomycin and fosfomycin on methicillin-resistant Staphylococcus aureus from antibiotic-impregnated articulating cement spacers. Bone Joint Res 2017;6:132–136. DOI: 10.1302/2046-3758.63.2000639

Objectives. Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature. Methods. In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1

1. We have shown that the permeability of cartilage is the same in necropsy specimens as in the living animal. We have concluded that studies of material transport into cartilage carried out on necropsy specimens validly reflect in vivo conditions. 2. We have studied the effect of agitation of the fluid in which cartilage is immersed upon the rate of diffusion of substances into cartilage and have found that agitation increases the rate of penetration up to three or four fold. We believe that it may be inferred from this fact that the nutrition of cartilage is partly dependent on joint movement. 3. We have examined the permeability of the bone-cartilage interface to water and solutes and have found that in the adult no detectable material transfer occurs across this zone. In the child on the other hand the bone-cartilage interface appears to be permeable to water and solutes. 4. We have measured the diffusion coefficient of glucose in cartilage and have hence estimated the depth of cartilage which can be adequately supplied with glucose from the synovial fluid in the presence and absence of agitation. 5. We have examined both experimentally and theoretically the possible effect of intermittent loading on the rate of penetration of substances into cartilage. We have concluded that at low pressures intermittent loading contributes little to the material transfer into cartilage. At high pressures intermittent loading does lead to the transport of solutes into cartilage but it cannot significantly increase the rate of transfer above that attributable to normal diffusion. Loading cartilage surfaces for prolonged periods of time without allowing intermittent relaxation would be expected to lead to decreased diffusion, without any absorption of fresh fluid attributable to the action of a pump, and would thus result in an overall decrease in the rate of penetration of substances into cartilage

1. The hyaluronate of synovial fluid is an acidic linear polymer which can effectively resist the diffusion of other macromolecules into its domain. Gelatin was used as an experimental model for hyaluronate, to investigate its effect upon the diffusion of protein-polysaccharides from cartilage slices. 2. The concentration of protein-polysaccilaride in the extracting medium was quantitated by uronic acid estimation and liquid scintillation spectrometry of . 35. sulphate-labelled proteinpolysaccharide. 3. Concentrations of gelatin in excess of 20 per cent (W/v) significantly retarded diffusion of protein-polysaccharides out of cartilage slices, but evidently not the movement of these molecules within cartilage. 4. It is suggested that disaggregation of both the protein-polysaecharide molecules of cartilage and the hyaluronate of synovial fluid contribute to cartilage breakdown

The release of gentamicin sulphate, sodium fusidate and diethanolamine fusidate from Palacos and CMW cements was studied using elution and serial plate transfer tests. Further tests were made to assay the drug remaining in the cement after antibacterial activity could no longer be detected by the above methods, to detect the sustained slow release of the residual drug, and to ascertain the mechanism of release. The results confirmed that the release of gentamicin sulphate could be detected for longer from Palacos cement than from CMW cement, but the opposite was true for sodium fusidate. Little difference was found in the case of diethanolamine fusidate. Comparison of elution and serial plate transfer tests, and of results of elution in buffers of different pH, demonstrated that the test method employed had a significant effect on the results, and the omission of details of methodology from some publications made comparison and evaluation of results difficult. Varying quantities of residual drug were found in cement from which antibacterial activity could no longer be demonstrated; further tests for sustained, slow release showed that the antibiotic did not remain fixed in the cement but was released at a rate too slow to be detected in the elution and serial plate transfer tests. It is concluded that antibiotics are released from the cement by a process of diffusion, but tests to determine the mechanism of diffusion were unhelpful. The theory of diffusion of drugs through solid matrices, and the clinical implications of the experimental findings, are discussed

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria. We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive. We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (. sd. 15.7) to 124.6 (. sd. 46.2) in periosteal bone for gentamicin and 31.9 (. sd. 8.9) in endosteal and 2.9 (. sd. 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds

The release of various penicillins and other antibiotics from two brands of polymerised bone cement has been studied in vitro and in vivo in mice. Bone cement plugs containing antibiotics demonstrated antibacterial activity as a result of diffusion of antibiotic from the plugs into the surrounding medium. With all antibiotics tested, from 2-5 to 10 per cent of the antibiotic in the cement was released in vitro in active form within twenty-four hours. Most of the activity appeared within three hours of the start of the test, but in some cases low levels of activity were detected after four days. Antibiotic cement plugs implanted in mice and rats produced low concentrations of antibiotic in the blood up to two hours after implantation, but activity was seldom detected subsequently. In general, penicillins and non-penicillin antibiotics showed similar diffusion characteristics, and the pattern of release in vitro and in vivo was consistent with the leaching of antibiotic from, or near, the surface of the bone cement

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell’s technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell’s work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.

Cite this article: Bone Joint J 2023;105-B(1):11–16.

Aims

Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.