Identifying Research Priorities in Limb Reconstruction Surgery in the United Kingdom.

Introduction: Limb reconstruction surgery (LRS) has a wide range of clinical applications within orthopaedic and trauma surgery. We sought a consensus view from limb reconstruction healthcare practitioners across the United Kingdom to help guide research priorities within LRS. Our aim is to guide future clinical research in LRS, and assist healthcare practitioners, clinical academics, and funding bodies in identifying key research priorities to improve patient care. Materials and methods: A modified Delphi approach was used; it involved an initial scoping survey and a 2-round Delphi process to identify the consensus research priorities in both adult and paediatric LRS. Participants were asked to rank approved submitted questions according to perceived importance on a 5-point Likert scale, where 1 represented lowest importance and 5 indicated highest importance. Mean scores were calculated to identify a consensus of the top ten research priorities for adult and paediatric LRS. Results: One hundred and fifteen participants primarily from across the United Kingdom working in LRS contributed to the modified Delphi process. Participants ranked and then re-ranked the presented research topics in terms of perceived importance. This led to the identification of a top ten research priorities in both adult and paediatric LRS, respectively, based on the collective responses of LRS practitioners. The highest-ranked questions in both adult and paediatric practice related to how to best assess and record patient-reported outcome measures (PROMs) in LRS patients. Other priorities included the effectiveness of specialist physiotherapy, the use of patient-focused psychological support, and the use of various operative management strategies for infection and limb length discrepancies. Conclusion: We present a consensus-driven research priority study that outlines the key research topics and themes determined by healthcare professionals within LRS in the United Kingdom. Clinical significance: These questions will assist funding bodies in prioritising where research funding may be best utilised and help drive future improvement in patient care. How to cite this article: British Limb Reconstruction Society Research Collaborative. Identifying Research Priorities in Limb Reconstruction Surgery in the United Kingdom. Strategies Trauma Limb Reconstr 2024;19(1):1-8.

Optimising the Orthopaedic Trauma Society Open Fracture Classification system: a proposal for modification in the context of high civilian gunshot fractures.

OBJECTIVES: Uniformly classifying long bone open fractures is challenging. The purpose of this study was to propose a modified Orthopaedic Trauma Society (OTS) Open Fracture Classification System, developed in a setting with a high incidence of civilian gunshot fractures. METHODS: From our prospectively collected database, we identified all patients with open tibia and femur fractures treated with intramedullary nailing over a 4 year period. All open fractures were retrospectively reclassified from the Gustilo-Anderson Classification system to the OTS Open Fracture Classification System. RESULTS: One hundred and thirty-seven cases were identified. Ninety per cent of subjects were males. Their mean age was 34 years. The most common mechanism of injury was low-velocity civilian gunshot wounds (GSW) in 54.7% of cases. Soft tissue management was primary closure in 23.4% and soft tissue reconstruction in 24.1%. In 52.6% of cases (these all being secondary to civilian GSW), soft tissue management was healing via secondary intention. This is not included as a soft tissue management option in the OTS classification system. Fracture reclassification using the OTS Open Fracture Classification System was only possible in 47.5% of cases (Simple in 23.4%, Complex B in 24.1%). CONCLUSION: We conclude that the OTS Open Fracture Classification System is not inclusive of all open tibia and femur fractures as it does not cater for gunshot fractures. We propose a modification as follows: alter 'wound debridement' to 'appropriate wound care' and to subcategorise 'Simple' into type A and B: healing via secondary intention and primary closure, respectively.

Circular External Fixator Removal in the Outpatient Clinic Using Regional Anaesthesia: A Pilot Study of a Novel Approach.

Introduction: External fixator (EF) devices are commonly used in the management of complex skeletal trauma, as well as in elective limb reconstruction surgery for the management of congenital and acquired pathology. The subsequent removal of an EF is commonly performed under general anaesthesia in an operating theatre. This practice is resource-intensive and limits the amount of time available for other surgical cases in the operating theatre. We aimed to assess the use of regional anaesthesia as an alternative method of analgesia to facilitate the EF removal in an outpatient setting. Design and methods: This prospective case series evaluated the first 50 consecutive cases of EF removal in the outpatient clinic between 10/06/22 and 03/02/23. Regional anaesthesia using ultrasound-guided blockade of peripheral nerves was administered using 1% lidocaine due to its rapid onset and short half-life. Patients were assessed for additional analgesia requirements and then were asked to evaluate their experience and perceived pain using the visual analogue scale (VAS). Results: Fifty patients were included in the study. The mean age was 46.8 years (range 21-85 years). About 54% of the patients were male patients (N = 27). Post-procedure, all patients indicated positive satisfaction ratings, each participant responded as either 'satisfied' (N = 6), 'very satisfied' (N = 24) or 'highly satisfied' (N = 20). In addition, 90% of the participants reported that they would opt for this method of EF removal again in future. The VAS for pain immediately following completion of the procedure was low, with a mean score of 0.36 (range 0-4), where a score of 0 = 'No pain', and 10 = 'worst pain possible'. The median score was 0. Conclusion: We present the first description of outpatient EF removal using regional anaesthesia, with a prospective case series of 50 fully conscious patients from whom the EF was removed. This novel technique is likely to be cost-effective, reproducible, and safe. This technique reduces the burden of EF removal from an operating list and also improves the patient's experience when compared with other forms of conscious sedation. By eliminating the use of Entonox and methoxyflurane for sedation and analgesia, this technique also demonstrates a method of improving environmental sustainability. How to cite this article: Williams LM, Stamps G, Peak H, et al. Circular External Fixator Removal in the Outpatient Clinic Using Regional Anaesthesia: A Pilot Study of A Novel Approach. Strategies Trauma Limb Reconstr 2023;18(1):7-11.

Return to Work Following Intramedullary Nailing of Lower-Limb Long-Bone Fractures in South Africa.

BACKGROUND: Injuries are one of the leading causes of global death and disability and commonly have substantial economic implications. The economic impact of injuries is particularly pronounced in low- and middle-income countries, where 90% of injuries occur. In this study, we aimed to assess return-to-work rates of individuals who sustained a lower-limb long-bone fracture in South Africa and to identify factors that influence the ability to return to employment. METHODS: This prospective cohort study was conducted across 2 tertiary trauma centers in Cape Town, South Africa. Adults who received intramedullary nail fixation for a lower-limb fracture between September 2017 and December 2018 were recruited and followed for 18 months postoperatively. The participants' return to employment was assessed at 6 and 18 months post-injury. Multivariate logistic regression was used to identify factors that influence post-injury employment. RESULTS: Of the 194 participants enrolled, 192 completed follow-up. The study population had a median age of 33.0 years, and most of the participants (76.6%) were male. Seventy-five percent of the participants were employed before their injury. At 6 and 18 months post-injury, 34.4% and 56.3% of participants, respectively, were employed. Of those employed pre-injury, 70.1% had returned to work at 18 months. Multivariate regression identified increasing age, unemployment prior to injury, and working in the informal employment sector as factors that impede an individual's likelihood of working 18 months post-injury. For those in employment prior to injury, increasing age was the only factor found to impede the likelihood of returning to work following an injury. CONCLUSIONS: This study highlights the profound effect that lower-limb long-bone fractures may have on an individual's ability to return to work in South Africa, with the potential to cause substantial economic impact on an individual's livelihood and that of their dependents. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

The reuse of circular external fixator components: an assessment of safety and potential savings.

PURPOSE: Cost-saving strategies are important, especially in a resource-constrained environment. One such strategy well supported in the literature is the reuse of temporary monolateral external fixator components, a strategy we utilize at our institution. The aim of the study was to determine the safety and cost saving associated with the reuse of definitive circular external fixator components in a resource-constrained environment. METHOD: We performed a retrospective review of all adult patients who were treated with either new or reused circular external fixators from a single manufacturer between January and December 2017. Reused circular external fixator components, excluding half pins and wires, were subjected to an in-house reprocessing protocol. Cost savings were calculated as the difference between the price of a completely new frame and the amount invoiced for new components only in a reused frame. RESULTS: Thirty-three patients were included in the study with an average age of 31.9 years. The mean duration of treatment with a circular external fixator was 5.8 months. No mechanical failure events were recorded during the study period. Our institution saved approximately 52% (R717 503.89) and 63% (R136 568.19) of expected total cost for hexapod and Ilizarov frames, respectively. CONCLUSION: The strategy of reusing circular external fixator components is unconventional, and this study was conducted to evaluate the safety and potential savings in a resource-constrained environment. We demonstrated this practice to be reasonably safe and to result in significant cost savings which might be relevant in low-and-middle-income countries.

Clinical outcomes of ankle fractures in sub-Saharan Africa: a systematic review.

PURPOSE: Ankle fractures may cause disability and socioeconomic challenges, even when managed in a high-resource setting. The outcomes of ankle fractures in sub-Saharan Africa are not widely reported. We present a systematic review of the patient-reported outcomes and complications of patients treated for ankle fractures in sub-Saharan Africa. METHODS: Medline, Embase, Google Scholar and the Cochrane Central Register of Controlled Trials were searched, utilising MeSH headings and Boolean search strategies. Ten papers were included. Data included patient demographics, surgical and non-surgical management, patient-reported outcome measures and evidence of complications. RESULTS: A total of 555 patients with ankle fractures were included, 471 of whom were followed up (range 6 weeks-73 months). A heterogenous mix of low-quality observational studies and two methodologically poor-quality randomised trials demonstrated mixed outcomes. A preference for surgical management was found within the published studies with 87% of closed fractures being treated operatively. A total of five different outcome scoring systems were used. Most studies included in this review were published by well-resourced organisations and as such are not representative of the actual clinical practice taking place. CONCLUSION: The literature surrounding the clinical outcomes of ankle fractures in sub-Saharan Africa is sparse. There appears to be a preference for surgical fixation in the published literature and considering the limitations in surgical resources across sub-Saharan Africa this may not be representative of real-life care in the region.

Radiographic union score for tibia (RUST) scoring system in adult diaphyseal femoral fractures treated with intramedullary nailing: an assessment of interobserver and intraobserver reliability.

OBJECTIVES: The Radiographic Union Score for Tibia (RUST) scoring system has been validated in multiple studies assessing the healing of tibial fractures. Our objective was to assess the interobserver and intraobserver reliability for the RUST in diaphyseal femoral fractures treated with intramedullary (IM) nailing. PATIENTS AND METHODS: A total of 60 sets of anteroposterior (AP) and lateral radiographs of diaphyseal femoral fractures treated by reamed IM nailing were randomly selected from a prospectively collected database. The 60 sets of radiographs were then scored by three reviewers using the RUST system. Interobserver reliability was measured at initial scoring. The 60 sets of radiographs were scored again by the three reviewers to calculate the intraobserver reliability. RESULTS: The RUST scores ranged from 4 to 12 with a mean score of 11.3 ± 1.3. The interobserver intraclass correlation coefficient (ICC) was 0.87 (95% CI, 0.81-0.92) and the intraobserver ICC was 0.91 (95% CI, 0.88-0.94), which indicated excellent agreement. CONCLUSION: This study demonstrated that the RUST system can be used reliably in the assessment of healing in diaphyseal femur fractures treated by reamed intramedullary nailing, with excellent interobserver and intraobserver reliability.

Train related injuries: A descriptive analysis highlighting orthopaedic injuries and management.

INTRODUCTION: Orthopaedic injuries constitute a major aspect of morbidity and mortality following train accidents. The pattern of orthopaedic/musculoskeletal injuries sustained following these accidents has not been fully characterised. The main aim of this study is to describe the range of orthopaedic injuries reported in a major trauma centre and evaluate their management, as well as reporting mortality and amputation rates. Further aims are to identify the social and demographic background of the patients to suggest treatment and prevention strategies. METHODS: This study is a retrospective observation of all clinical files of patients presented to Level 1 Trauma Centre in Cape Town, South Africa, as "train casualty" from January 2013 to July 2019, which were reviewed and evaluated. A total of 174 patients were included, of which 92 were orthopaedic referrals. The average age was 29 years, and 87% were male. RESULTS: Tibial fractures were most common (N = 19), 38% of patients sustained open fractures, and 68% of patients (in total) underwent surgery. Wound debridement was the most common operation, followed by open reduction internal fixation (ORIF). Twelve patients (13%) underwent amputation to 14 body parts. Eight patients (4.6%) (in total) died in the trauma unit. DISCUSSION: This study provides insight into train accident victims and their orthopaedic injuries and management patterns. The victims are largely young males. The majority of orthopaedic injuries require surgical intervention, and those who make it to the hospital have a good chance of survival and limb salvage. It appears that in addition to early hospital access and specialised updated treatments, morbidity and mortality in train accidents could be reduced by improving safety measures and social awareness to reduce railway violence and accidents.

Bibliometric analysis of research on the effects of human immunodeficiency virus in orthopaedic and trauma surgery.

BACKGROUND: There is little research investigating how human immunodeficiency virus (HIV) affects outcomes in orthopaedic surgery. With advances in treatment, HIV has become a chronic health problem and the chance of orthopaedic surgeons encountering it in clinical practice is increasing. AIM: To ascertain the quantity and quality of peer-reviewed publications in orthopaedic journals about HIV. METHODS: A search of the Web of Science database was carried out, identifying any articles relating to HIV published in orthopaedic journals. These were assessed for geographic origin and level of evidence. RESULTS: Of 48.7% of orthopaedic journals listed on the Web of Science database had published articles relating to HIV. There were 168 articles about HIV in orthopaedic journals with only 40.5% (n = 68) published in the time frame we analysed (January 2007 to September 2017). Very few articles came from low-income countries and any articles published from that setting were collaborations. All of the articles were low level of evidence. CONCLUSION: There is a need for more high level orthopaedic and trauma research investigating the effects of HIV, particularly research from low-income countries, where higher level research will help to guide improvements in their treatment of its musculoskeletal manifestations and complications.

Civilian gunshot injuries in orthopaedics: a narrative review of ballistics, current concepts, and the South African experience.

The incidence of civilian gunshot injuries is on the rise worldwide.Unfortunately, there is a lack of high-level evidence guiding management. The treatment of orthopaedic injuries from gunshots is complex and requires consideration of multiple aspects, including energy transfer to the tissue, severity of the wound, possible contamination, presence of fractures and associated injuries. With this narrative review we aim to discuss some of the relevant ballistics, current concepts, and controversies in the general management of civilian gunshot-related orthopaedic injuries based on the available evidence and personal experience. Important points which will be highlighted are the initial management in the emergency room, the assessment and management of soft tissue injuries, associated injuries, use of antibiotics, indication and techniques for fracture fixation, and gunshot injuries to joints.

Total Hip Arthroplasty in a Low-Income Country: Ten-Year Outcomes from the National Joint Registry of the Malawi Orthopaedic Association.

We describe our 10-year experience performing total hip arthroplasty (THA) in patients enrolled in the National Joint Registry of the Malawi Orthopaedic Association. METHODS: Eighty-three THAs were performed in 70 patients (40 male and 30 female) with a mean age of 52 years (range, 18 to 77 years). The cohort included 24 patients (14 male and 10 female; mean age, 52 years [range, 35 to 78 years]) who were human immunodeficiency virus (HIV)-positive. RESULTS: The main indications for surgery were osteonecrosis (n = 41 hips) and osteoarthritis (n = 26 hips). There were no deaths perioperatively and no early complications at 6 weeks. Forty-six patients (59 THAs) were seen at 10 years postoperatively, with a mean Harris hip score (HHS) of 88 (range, 41 to 91) and a mean Oxford Hip Score (OHS) of 46 (range, 25 to 48). Five hips (8% of 59) were revised due to loosening (n = 4) and fracture (n = 1). There were no infections or dislocations. Fourteen patients died, including 4 HIV-positive patients, of unknown causes in the follow-up period, and 10 patients were lost to follow-up. In the group of 24 HIV-positive patients, there were no early complications, and the mean HHS was 88 (range, 76 to 91) at >10 years. CONCLUSIONS: Our 10-year experience and long-term outcomes after primary THA in a low-income setting show that good results can be achieved within a controlled hospital environment, thereby establishing a benchmark against which other hospitals and registries in similar low-income countries can compare their results. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Total Knee Arthroplasty in a Low-Income Country: Short-Term Outcomes from a National Joint Registry.

BACKGROUND: We describe our 10-year experience with total knee arthroplasty in patients who are included in the Malawi National Joint Registry. METHODS: A total of 127 patients underwent 153 total knee arthroplasties (TKAs) between 2005 and 2015. The mean duration of follow-up was 4 years and 3 months (range, 6 months to 10 years and 6 months). The study group included 98 women and 29 men with a mean age of 65.3 years (range, 24 to 84 years). Nine patients were human immunodeficiency virus (HIV)-positive. RESULTS: The primary indication for surgery was osteoarthritis (150 knees), and the mean preoperative and postoperative Oxford Knee Scores were 16.81 (range, 4 to 36) and 45.61 (range, 29 to 48), respectively. Four knees (2.6%) were revised because of early periprosthetic joint infection (1 knee), aseptic loosening (1 knee), and late periprosthetic joint infection (2 knees). There were no perioperative deaths. In the group of 9 patients who were HIV-positive, there were no early or late complications and the mean Oxford Knee Score was 47 (range, 42 to 48) at the time of the latest follow-up. CONCLUSIONS: This study demonstrated good short-term results following 153 primary TKAs performed in a low-income country. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Fracture management in HIV positive individuals: a systematic review.

PURPOSE: Human immunodeficiency virus (HIV) infection could potentially play an important role in the management of fractures as they have been shown to affect fracture healing and the post-operative risk of implant sepsis. METHODS: A systematic review of the relevant literature was performed on PubMed and Scopus databases. Twenty-six studies were identified, critiqued and analysed accordingly. No randomised controlled trials were identified. RESULTS: HIV positivity was not shown to influence an individual's risk of early wound infection in operatively managed closed fractures. The rate of pin track infection in open injuries managed with external fixators was low. However, in open injuries managed with internal fixation, early wound infection rates were increased in the HIV-positive population compared to HIV-negative individuals. Regarding late implant infection, in closed fractures there appeared to be no increased risk of infection but there is limited evidence for open injuries. Additionally, further evidence is needed to establish if the rate of union in both open and closed fractures are influenced by HIV status. CONCLUSION: Overall, no evidence was found to suggest that surgical management of fractures in the HIV population should be avoided, and fixation of closed fractures in the HIV population appeared to be safe. The effect of anti-retroviral therapy is unclear and this should be further researched. However, based on the limited evidence, caution should be taken in the management of open fractures due to the potentially increased infection risk. The impact of anti-retroviral therapy on the outcomes of surgery needs further evaluation.

Late implant sepsis after fracture surgery in HIV positive patients.

A prospective cohort study was undertaken to assess the incidence of late-implant sepsis after internal fixation in HIV-positive patients. A total of 91 HIV-positive patients (67 males and 24 females) who underwent 103 procedures (111 implants) were followed up for a mean period of 27 months (range 12-66 months). No occurrences of late implant sepsis were found in 100 implants (94 procedures) in 82 patients at 27 months' follow-up (range 12-66 months). Nine patients (9 procedures, 9 implants) developed early infections within 6 weeks and were treated with antibiotics (6 patients), amputation (1 patient) or removal of metal work (2 patients). There was no evidence of subsequent late implant sepsis in any of these patients, at a mean follow-up of 25 months (range 12-52 months). This study demonstrates that it is safe to perform internal fixation in HIV-positive patients, with no observed increase risk of late implant sepsis. There is no indication to remove implants after fracture union, other than for the general clinical indications that may lead to removal of metal work in any patient.

Clinical results of linezolid in arthroplasty and trauma MRSA related infections.

AIM: To analyse the management of patients treated with linezolid for orthopaedic infections. METHODS: Twenty-two patients with orthopaedic related infections receiving a course of linezolid were reviewed retrospectively. Patients were classified into either post trauma, post arthroplasty and non trauma related infections. A diagnosis of infection was based on clinical findings, positive microbiological specimens, and positive signs of infection on radiological imaging and raised inflammatory markers. Pathogens isolated, inflammatory markers both at presentation and at final follow up, length of linezolid treatment, adverse drug reactions, concomitant anti-microbial therapy, length of hospital stay and any surgical interventions were recorded. RESULTS: Infections were classified as post arthroplasty (n = 10), post trauma surgery (n = 8) or non-trauma related infections (n = 4). Twenty patients (91%) underwent surgical intervention as part of their treatment. The number of required surgical procedures ranged from 1 to 6 (mean = 2.56). Mean total length of stay per admission was 28.5 d (range 1-160 d). Furthermore, the mean duration of treatment with linezolid of patients who had resolution of symptoms was 31 d (range 10-84 d). All patients within this group were discharged on oral linezolid. Pathogens isolated included methicillin resistant Staphylococcus aureus, coagulase negative staphylococci, coliforms, enterococcus, Staphylococcus epidermidis, streptococcus viridans, Escherichia coli, group B streptococcus and pseudomonas. An overall 77% of patients demonstrated resolution of infections at follow-up, with mean C-reactive protein reducing from 123 mg/L to 13.2 mg/L. CONCLUSION: This study demonstrates that the use of linezolid offers excellent efficacy in orthopaedic related infections when used alongside appropriate surgical management.

The management gram-negative bacterial haematogenous vertebral osteomyelitis: a case series of diagnosis, treatment and therapeutic outcomes.

PURPOSE: The incidence of gram-negative bacterial haematogenous vertebral osteomyelitis (GNB HVO) is increasing. We performed a retrospective cohort study of patients with this type of infection in an effort to gain an improved understanding of the current clinical presentation, management and outcome. METHODS: Between May 2007 and May 2010, all patients, over the age of 18 years, suffering from GNB HVO were identified and their microbiological diagnoses were evaluated. RESULTS: This study identified seventy-nine patients with haematogenous vertebral osteomyelitis (HVO). Of these seventy-nine patients, 10 patients (12.66%) had Gram-negative organisms isolated. These organisms included Escherichia coli (4), Pseudomonas aeruginosa (3), Klebsiella pneumonia (1), Haemophilus influenza (1) and Enterobacter cloacae (1). Eight patients were successfully treated with antibiotics and/or surgery. Of the eight patients whose HVO was cured, five had Ciprofloxacin as part of their definitive antibiotic regime. CONCLUSION: The treatment of GNB HVO is often challenging because of unpredictable resistance patterns and limited published data on effective treatment regimens. Our study has highlighted the need for prompt microbiological sampling and initiation of early appropriate antibiotic regime. The most effective treatment for GNB HVO was with oral Ciprofloxacin over a period of 6-8 weeks.

The in vitro and in vivo effects of nicotine on bone, bone cells and fracture repair.

INTRODUCTION: Cigarette smoke has negative effects on bone metabolism and fracture repair. However, no study has reviewed effects of nicotine on bone and fracture repair independent of other constituents of cigarette smoke. The authors review the existing evidence of the effect of nicotine on 'bone' and 'bone cells' and fracture repair, drawing conclusions relevant to clinical practice and future research. AREAS COVERED: A literature review was conducted using PRISMA guidelines and PubMed, Cochrane, MEDLINE/OVID, EMBASE, NHS Evidence and Google scholar databases. Articles were included if they specifically investigated the effects of nicotine on 'bone' or fracture repair in animal or human models or in vitro effects on 'bone cells'. A total of 64 papers were included in this review, of which 15 were human in vitro studies and 49 animal studies wherein 9 were in vitro and 40 in vivo. In vivo studies of the effects of nicotine in animals demonstrated widespread effects on bone including osteoneogenesis, osseointegration, steady-state skeletal bone and genes and cytokines relevant to bone cell physiology and bone homeostasis. In these studies, nicotine's effects are predominately negative, inhibiting bone cell metabolism and fracture repair, whereas most in vitro studies reported biphasic responses in all bone cells except osteoclastic cells. EXPERT OPINION: The review suggests that nicotine has effects on osteoneogenesis, osseointegration and steady-state skeletal bone in animal in vivo models, as well as effects on all 'bone cells', via several mechanisms in both animal and human cell in vitro studies. The effect of nicotine is dose-dependent, with higher concentrations having predominantly negative effects, whereas at low concentrations a stimulatory effect is seen. Stimulatory effects on certain cells may indicate a possible, limited therapeutic role; advice regarding smoking cessation perioperatively should remain due to the other harmful components of cigarette smoke, but there may be scope for allowing the use of nicotine patches instead of complete abstention. Further research into clinical outcomes is required before the exact response of bone and fracture repair in humans to nicotine is known.

Anti-inflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: potential for treatment.

INTRODUCTION: Mesenchymal stem cells (MSCs) are multipotent stromal cells characterized by their ability to differentiate into adipocytes, chondrocytes, osteocytes and a number of other lineages. Investigation into their use has increased in recent years as characterization of their immunomodulatory properties has developed, and their role in the pathophysiology of joint disease has been suggested. AREAS COVERED: MSCs demonstrate immunosuppressive functionality by suppressing T- and B-cell responses following activation by cytokines such as IL-6 and IL-1α. They also can be induced to exert pro-inflammatory effects in the presence of acute inflammatory environment due to the actions of TNF-α and IFN-γ. In inflammatory joint diseases such as rheumatoid arthritis, MSCs in bone marrow migrate to joints by a TNF-α-dependent mechanism and may be in part responsible for the disease process. MSCs have also been demonstrated in increased numbers in periarticular tissues in osteoarthritis, which may reflect an attempt at joint regeneration. EXPERT OPINION: Clinical applications for MSCs have shown promise in a number of inflammatory and autoimmune disorders. Future work is likely to further reveal the immunosuppressive characteristics of MSCs, their role in the pathophysiology of joint diseases and provide the basis for new avenues for treatment.