Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis.

More than 40% of individuals will develop osteoarthritis (OA) during their lifetime, yet there are currently no licensed disease-modifying treatments for this disabling condition. Common polymorphic variants in ALDH1A2, which encodes the key enzyme for synthesis of all-trans retinoic acid (atRA), are associated with severe hand OA. Here, we sought to elucidate the biological significance of this association. We first confirmed that ALDH1A2 risk variants were associated with hand OA in the U.K. Biobank. Articular cartilage was acquired from 33 individuals with hand OA at the time of routine hand OA surgery. After stratification by genotype, RNA sequencing was performed. A reciprocal relationship between ALDH1A2 mRNA and inflammatory genes was observed. Articular cartilage injury up-regulated similar inflammatory genes by a process that we have previously termed mechanoflammation, which we believe is a primary driver of OA. Cartilage injury was also associated with a concomitant drop in atRA-inducible genes, which were used as a surrogate measure of cellular atRA concentration. Both responses to injury were reversed using talarozole, a retinoic acid metabolism blocking agent (RAMBA). Suppression of mechanoflammation by talarozole was mediated by a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Talarozole was able to suppress mechano-inflammatory genes in articular cartilage in vivo 6 hours after mouse knee joint destabilization and reduced cartilage degradation and osteophyte formation after 26 days. These data show that boosting atRA suppresses mechanoflammation in the articular cartilage in vitro and in vivo and identifies RAMBAs as potential disease-modifying drugs for OA.

Population Study of Hand and Wrist Manifestations of Congenital Insensitivity to Pain.

Background: Congenital insensitivity to pain is a rare autosomal recessive condition characterized by insensitivity to painful stimuli due to absence of sensory and sympathetic post ganglionic neurons in the skin and skeletal system leading to lack of protective sensation and altered joint propioception. This study was performed to assess hand and wrist manifestations of patients with congenital insensitivity to pain in the Maltese Islands. Methods: Records of public and private hospitals were reviewed to identify patients suffering from this condition. A review of notes, patients, and imaging was performed. A Disabilities of the Arm, Shoulder, and Hand score was obtained to assess level of function. Results: Nine patients were identified. Mean age of diagnosis was 8.9 years. Interphalangeal joints were most commonly affected. Multiple spontaneous or posttraumatic fingertip ulceration occurred in 5 patients. Anhidrosis resulted in more protracted ulcers and infections, requiring amputation of distal and middle phalanges due to osteomyelitis. The wrist joint was less commonly involved and showed more complex joint involvement. Conclusion: The hand and wrist are involved in different ways, with fingertip ulceration leading to potential infection and osteomyelitis in the hand, whereas the wrist joint is involved in cases of increased axial loading and load transfer, such as following prolonged use of walking and mobility aids. The latter should be borne in mind during management of lower limb conditions. Hand care and hygiene is important in all patients, especially in cases of anhidrosis due to the increased rate of ulceration and osteomyelitis requiring surgical intervention. Despite the severity of the condition, patients report good overall function.

Systematic Review of Thumb Carpometacarpal Joint Hemiresection Interposition Arthroplasty Materials.

BACKGROUND: Osteoarthritis of the first carpometacarpal joint is a common condition. Various management options and surgical procedures have been described to treat symptomatic cases. Many systematic reviews examine aspects of thumb carpometacarpal joint osteoarthritis treatment, although none solely examines the outcomes of trapezial partial resection and interposition arthroplasty in stage II to III patients in detail, yet this technique is of growing interest as surgeons seek more nuanced, tailored approaches for osteoarthritis of the first carpometacarpal joint. METHODS: A systematic review of the thumb carpometacarpal joint hemiresection and interposition arthroplasty was performed with pain assessment as a primary outcome measure and patient-reported outcome measures (PROMs) and reoperation rate as secondary outcome measures. A search was performed between 2004 and 2019 using MEDLINE, Embase, and PubMed. Preferred Reporting Items and Systematic Reviews and Meta-Analyses guidelines were used. RESULTS: Twenty-nine articles met the inclusion criteria and were included in the final review. Pain relief and improved PROMs were described in all the articles using this technique with all the interposition materials. Materials such as polyurethane urea matrix and poly-l/d-lactide scaffold had higher complication rates. Revision rates varied and were highest with the polyurethane urea matrix. CONCLUSIONS: This review shows that hemiresection interposition arthroplasty is a useful technique and provides symptomatic benefit in patients with Eaton-Littler stage II and III osteoarthritis. Revision surgery rates due to persistent pain and instability were higher with the use of implants. Larger and long-term studies of this technique using autologous or more bioinert materials and implants are required to assess duration of symptomatic benefit.

Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges.

Vascularised composite allograft (VCA) transplantation is now a feasible reconstructive option for patients who have suffered significant soft tissue injuries. However, despite numerous technical advances in the field over two decades, a number of challenges remain, not least the management of transplant rejection. Part of the difficulty faced by clinicians is the early recognition and prevention of acute rejection episodes. Whilst this is potentially easier in VCAs than solid organ transplants, due to their visible skin component, at present the only validated method for the diagnosis of acute rejection is histological examination of a tissue biopsy. The aim of this review article is to provide an evidence-based overview of progress in the field of VCA biomarker discovery, including immune cell subsets, immune cell effector pathways, and circulating markers of allograft damage, and to discuss future challenges in the field.

Vascularised composite allotransplantation in solid organ transplant recipients: A systematic review.

INTRODUCTION: A solid organ transplant (SOT) recipient, already taking immunosuppression, may represent the ideal candidate for vascularised composite allograft transplantation (VCA). However, concerns have been raised about the potential risk of SOT loss or the need for increased immunosuppression to sustain the VCA. This systematic review examines all published cases of SOT recipients who have received a VCA to establish associated morbidity and immunosuppression requirements. METHODS: A systematic review was performed in accordance with the PRISMA guidelines. The PubMed, MEDLINE and EMBASE databases were searched for original articles published between January 1997 and May 2019. Only articles relating to patients who had received both a VCA and SOT with a reported follow up of greater than six months were included. RESULTS: Fifteen articles were identified, including data from 39 VCAs in 37 patients. There was no increase in the number of SOT rejection episodes, complications such as post-transplant lymphoproliferative disorder or graft versus host disease, de novo donor specific HLA antibodies or short-term risks to the recipient when compared with SOT in isolation. One child required a sustained increase in their baseline immunosuppression following bilateral hand transplantation. CONCLUSIONS: In this small heterogeneous cohort, the addition of a VCA to a SOT does not appear to increase the short-term risks to the SOT or the patient with comparable results to SOT in isolation. However, data are often poorly reported and longer-term follow up and uniform reporting of outcomes would be beneficial to more accurately assess the safety profile of combining VCA with SOT.

Outcome of arthrodesis for severe recurrent proximal interphalangeal joint contractures in Dupuytren's disease.

We report long-term outcomes of proximal interphalangeal joint arthrodesis for treatment of severe recurrent joint contractures secondary to Dupuytren's disease. The patients had at least two previous procedures for Dupuytren's contracture that involved the same joint, before undergoing joint fusion. Patient demographics, satisfaction, functional outcome, complications, revision and re-operation rates are reported. Eleven patients were included with a mean age of 64 years (range 53-73). The mean proximal interphalangeal joint contracture at presentation was 102° (range 80°-120°). None required revision surgery at a mean of 8 years and 9 months (range 9-199 months). All patients were able to perform their activities of daily living and would recommend this operation to family and friends. This series shows that proximal interphalangeal joint arthrodesis combined with needle fasciotomy or segmental fasciectomy provides a satisfactory salvage procedure in cases of severe recurrent Dupuytren's disease.Level of evidence: IV.

Free Vascularized Rectus Abdominis Transfer With Pedicled Intercostal Innervation for Functional Reconstruction of the Elbow in Total Brachial Plexus Palsy.

PURPOSE: Reanimation of palsied upper limbs usually follows an escalating pattern of nerve repair, nerve transfers, and musculotendinous transfers and culminates in free functioning muscle transfers. When there are no other musculotendinous options, we explored the possibility of transferring the rectus abdominus to the biceps by maintaining the nerve pedicle but dividing the vascular pedicle and anastomosing it to the brachial artery. METHODS: We performed anatomical dissection of the nerve and blood supply of 6 rectus abdominis muscles in 3 cadavers. A retrospective analysis of 4 patients in whom a rectus abdominus muscle transfer with a pedicled nerve, but free vascular supply, was then performed. RESULTS: The anatomical feasibility study demonstrated that it was possible to elevate the rectus abdominis on its intercostal nerve supply to the midaxillary line, allowing the muscle to be pedicled on its nerve supply and be transferred to the arm to reconstruct biceps. The vascular supply could be reestablished by anastomosis of inferior epigastric vessels to the brachial artery and veins. In 4 patients, elbow flexion strength of M3 or greater was achieved. Average elbow range of dynamic flexion was 120° (range, 92° to 131°). Shoulder stability and external rotation improved in all patients with resolution of shoulder subluxation. Two patients developed donor site hernias requiring mesh reconstruction. Complications included a hypertrophic recipient site scar in one patient, and recipient site wound dehiscence in another. CONCLUSIONS: Rectus abdominus can be transferred to reconstruct elbow flexion when other musculotendinous transfers are unavailable and as an alternative to free functioning muscle transfer. However, rectus abdominus transfer still requires microsurgical skills for the vessel anastomoses. This is an effective procedure for functional reconstruction of the elbow and adds to the armamentarium in the management of brachial plexus pathology when other transfers are unavailable. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

The Adipofascial Deltopectoral Flap to Cover the Brachial Plexus in Thoracic Outlet Syndrome and Radiation Plexitis.

Revascularisation of the brachial plexus is controversial. Traditional techniques use free tissue transfer of omentum, groin fat or muscle, on the principle of supplying rich quantities of vascularised tissue to wrap around the nerves permitting neural gliding and revascularising the scarred nerves. However, the complexity of an additional microsurgical procedure coupled with uncertainty of their effectiveness have curtailed their clinical application. We describe a local pedicled transposition flap that is a novel modification of the deltopectoral (DP) flap using only the subcutaneous adipofascial tissue vascularised by the medial pectoral perforators. This flap is harvested through the supraclavicular brachial plexus access incision. This avoids free tissue transfer and additional donor scarring, yet provides adequate volumes of well-vascularised tissue for mechanical protection and revascularisation of the plexus. We reviewed sixteen consecutive patients who underwent a pedicled adipofascial DP flap to protect the brachial plexus over the 20-year study period. Inclusion criteria were patients with recurrent thoracic outlet compression and patients with radiation plexitis. At latest follow-up (average 3.6 years), 75% of patients reported the improvement or resolution of symptoms. The majority of patients reported improved pain scores (82%) with an average pain visual analogue scale (VAS) score of 5.1. Patients were very satisfied with scar outcomes, reporting low Vancouver Scar Scale Scores and low scar VAS scores. Post-operative MR imaging, available in 31% of the cohort, demonstrates the maintenance of flap position and vascularity at an average of 2.1 years. This novel and simple technique is recommended in aiding revascularisation and cover of the brachial plexus in recurrent and recalcitrant plexopathy.

Surgical Techniques for Revascularization in Abdominal Wall Transplantation.

BACKGROUND: Abdominal wall vascularized composite allotransplantation (AW-VCA) can be considered as a technically feasible option for abdominal wall reconstruction in patients whose abdomen cannot be closed using traditional methods. However, successful initial abdominal wall revascularization in the setting of visceral organ transplantation can pose a major challenge as graft ischemia time, operating in a limited surgical field, and variable recipient and donor anatomy must be considered. Several techniques have been reported to accomplish abdominal wall revascularization. METHODS: A literature review was performed using PubMed for articles related to "abdominal wall transplantation (AWT)." The authors of this study sorted through this search for relevant publications that describe abdominal wall transplant anatomy, technical descriptions, and outcomes of various techniques. RESULTS: A total of four distinct revascularization techniques were found in the literature. Each of these techniques was described by the respective authors and reported varying patient outcomes. Levi et al published a landmark article in 2003 that described technical feasibility of AWT with anastomosis between donor external iliac and inferior epigastric vessels with recipient common iliac vessels in end-to-side fashion. Cipriani et al described a microsurgical technique with anastomosis between donor and recipient inferior epigastric vessels in an end-to-end fashion. Giele et al subsequently proposed banking the abdominal wall allograft in the forearm to reduce graft ischemia time. Recently, Erdmann et al described the utilization of an arteriovenous loop for synchronous revascularization of abdominal wall and visceral transplants for reduction of ischemia time, operative time, while eliminating the need for further operations. CONCLUSION: Vascularized composite allotransplantation continues to advance with improving immunotherapy and outcomes in solid organ transplantation. Optimizing surgical techniques remains paramount as the field continues to grow. Refinement of the presented methods will continue as additional evidence and outcomes become available in AW-VCA.

Current Strategies for Reconstruction of Soft Tissue Defects of the Spine.

Spinal surgery has been revolutionized by advances in instrumentation, bone graft substitutes, and perioperative care. Extensive dissection, creation of large areas of dead space, and the use of instrumentation in compromised patients, however, predisposes to high rates of wound complications. Postoperative wound complications in patients undergoing complex spinal surgery can have devastating sequelae, including hardware exposure, meningitis, and unplanned reoperation. Recognition of high-risk patients and prediction of wound closure difficulties, combined with preemptive reconstructive surgical strategies may prevent complications. The purpose of this review is to discuss the principles of spine wound management and provide a synopsis of the soft tissue reconstructive strategies utilized in spinal surgery. We review the senior author's preferred reconstructive algorithm for the management of these complex wounds, in addition to outcomes data relating to the timing of reconstructive surgery.

Radial nerve palsies associated with paediatric supracondylar humeral fractures: a caution in the interpretation of neurophysiological studies.

Traumatic and iatrogenic neurological complications associated with paediatric supracondylar humeral fractures are well recognised. The severity of the nerve injury associated with supracondylar humeral fractures can be difficult to assess clinically and relies upon clinical progression or absence of recovery and neurophysiology. It is accepted that complete nerve palsy with neurophysiological complete block and absence of clinical recovery after three months requires surgical exploration and reconstruction. However, we argue that even a partial nerve palsy that is failing to recover as expected by 3 months should be explored even when the neurophysiology suggests the nerve is in continuity. We report two cases of closed Gartland type III paediatric extension-type supracondylar humeral fractures treated with closed reduction and percutaneous pinning and open reduction and internal fixation, respectively. Both children developed persistent postoperative radial nerve motor palsy. Neurophysiological studies sought prior to exploration indicated a degree of sensory nerve function in both cases, indicating a nerve in continuity. Subsequent surgical exploration revealed interfragmentary radial nerve compression at the fracture site at two levels in one case and at one level in the second case. The site of compression was excised and the nerve grafted. Excellent near-normal radial nerve recovery was achieved except for the persistent loss of extensor carpi radialis function in the first child. We publish these findings to highlight the possibility of misinterpreting the incomplete nerve lesion and the neurophysiology of a nerve in continuity, as a nerve that would spontaneously recover. At exploration, in these two cases, it was clear by the level of interfragmentary compression that the nerve would not have recovered without surgical intervention. We recommend exploration and repair of the radial nerve, when function to the nerve is compromised, even in the face of neurophysiological evidence of an intact nerve.

The impact of intestinal transplantation on quality of life.

INTRODUCTION: Intestinal failure (IF) and intestinal transplant (ITx) are associated with poor quality of life (QoL). Disease-specific assessment of QoL for IF and ITx is challenging, owing to the different problems encountered. We have sought to compare QoL pre-ITx with post-ITx and have compared generic QoL with a stable IF population. METHODS: Two prospectively maintained databases of patients referred for and undergoing ITx and a chronic (Type 2 & 3) IF cohort were interrogated. QoL instruments used were generic (EQ-5D-5L and SF-36) and disease-specific (HPN-QOL and ITx-QOL). Analysis used Student's t-test and one-way ANOVA with Bonferroni correction for multiple comparisons. Data were collected pre- and post-ITx at 3, 6, 12-months and yearly thereafter. RESULTS: All QoL instruments improved following ITx to levels comparable with a cohort of stable IF patients not requiring ITx. Both the visual analogue score component (EQ-5D-5L) and the effect of underlying illness on QoL (HPN-QOL/ITx-QOL) were higher following ITx than either pre-ITx or when compared with the IF cohort. Effects on general health, ability to eat and drink, to holiday and travel were improved as early as 3 months post-ITx. Other components did not before 6-12 months following ITx, but were maintained to at least 24 months. Patient personal financial pressures are greater following ITx, even in a publicly funded healthcare system. CONCLUSION: ITx has beneficial effects on QoL compared to those assessed for or awaiting ITx. QoL following ITx is similar to patients with IF not requiring ITx. A QoL instrument that covers the journey of patients from IF through ITx would assist longitudinal analysis of the value and timing of ITx at an individual level.

The Effect of Age on Outcome in Excision of Chronic Osteomyelitis with Free Muscle Flap Reconstruction.

Introduction: Curative surgical treatment of chronic osteomyelitis often requires free tissue transfer if there is significant soft tissue compromise. We investigated whether age influenced outcomes of curative osteomyelitis excision in those patients requiring free muscle flap soft tissue reconstruction. Methods: We assessed ninety-five consecutive patients treated with excision of chronic osteomyelitis, skeletal stabilisation/reconstruction and free muscle transfer between 2006 and 2012. We compared outcomes of those aged ≥60 years (n=23) with those <60 years old (n=72). Results: Groups were similar with regard to Cierny and Mader anatomic type and physiological host classification. Length of procedure and length of hospital stay were similar for both groups. There was a greater proportion of ASA grade III patients in the older cohort. Infection recurrence occurred in one of the older cohort (4.3%) and in seven patients in the younger cohort (9.9%) at a mean follow-up of 42 months (range 11-131 months), this was not statistically significant (p=0.27874). There were five free flap losses (6.9%) in the younger group and none in the older group. A greater proportion of patients from the younger cohort required further unplanned surgery (28%) compared to the older group (4.3%), which was statistically significant (p=0.01174). Seven patients (7.4%) had serious medical complications - five of whom were in the younger cohort, including one mortality. Conclusions: Both the young and old can enjoy satisfactory outcomes from surgical resection of chronic osteomyelitis with simultaneous orthoplastic reconstruction including free tissue transfer. Age alone should not be a barrier to potentially curative surgical treatment.

Extrapolating novel techniques utilised in solid organ transplantation to the microsurgical and vascularised composite allograft arena.

Ischemia reperfusion injury (IRI) is characterised initially by restriction of oxygenated blood flow to an organ bed, resulting in tissue hypoxia and ischaemic injury, followed by further 'reperfusion' injury upon restoration of perfusion, with an influx of oxygen, inflammatory cells and generation of free radicals. The culmination is a complex interplay between cellular and biochemical processes involved in inflammation and coagulation, exhibited as the 'no re-flow' phenomenon. Under ideal circumstances, autologous free tissue transfer is performed with short ischemic times. However, there are certain clinical scenarios where the ischaemic period can be prolonged due to technical and non-technical factors. IRI is inevitable and can be possibly more pronounced in such cases. In these cases, there may be a role for plastic surgeons to adopt some of the anti-ischaemia reperfusion injury (IRI) practices used in solid organ transplantation (SOT). Knowledge of the current trends in SOT IRI reduction should be discussed by plastic surgeons to assess whether certain facets can be extrapolated into the plastic and reconstructive armamentarium. These can be applicable to more challenging microsurgical cases, including composite free tissue transfer. Three important aspects are discussed further in this editorial: (1) cold flushing, (2) machine perfusion and pharmacological manipulation. Ongoing research will need to study the impact these potential interventions will have on the acute complications but also in which subset of patients they would be most beneficial. This area is novel and exciting but cautious implementation is advised with careful scrutiny of future data.

Retrospective audit of 957 consecutive 18F-FDG PET-CT scans compared to CT and MRI in 493 patients with different histological subtypes of bone and soft tissue sarcoma.

BACKGROUND: The use of 18F-FDG PET-CT (PET-CT) is widespread in many cancer types compared to sarcoma. We report a large retrospective audit of PET-CT in bone and soft tissue sarcoma with varied grade in a single multi-disciplinary centre. We also sought to answer three questions. Firstly, the correlation between sarcoma sub-type and grade with 18FDG SUVmax, secondly, the practical uses of PET-CT in the clinical setting of staging (during initial diagnosis), restaging (new baseline prior to definitive intervention) and treatment response. Finally, we also attempted to evaluate the potential additional benefit of PET-CT over concurrent conventional CT and MRI. METHODS: A total of 957 consecutive PET-CT scans were performed in a single supra-regional centre in 493 sarcoma patients (excluding GIST) between 2007 and 2014. We compared, PET-CT SUVmax values in relation to histology and FNCCC grading. We compared PET-CT findings relative to concurrent conventional imaging (MRI and CT) in staging, restaging and treatment responses. RESULTS: High-grade (II/III) bone and soft tissue sarcoma correlated with high SUVmax, especially undifferentiated pleomorphic sarcoma, leiomyosarcoma, translocation induced sarcomas (Ewing, synovial, alveolar rhabdomyosarcoma), de-differentiated liposarcoma and osteosarcoma. Lower SUVmax values were observed in sarcomas of low histological grade (grade I), and in rare subtypes of intermediate grade soft tissue sarcoma (e.g. alveolar soft part sarcoma and solitary fibrous tumour). SUVmax variation was noted in malignant peripheral nerve sheath tumours, compared to the histologically benign plexiform neurofibroma, whereas PET-CT could clearly differentiate low from high-grade chondrosarcoma. We identified added utility of PET-CT in addition to MRI and CT in high-grade sarcoma of bone and soft tissues. An estimated 21% overall potential benefit was observed for PET-CT over CT/MRI, and in particular, in 'upstaging' of high-grade disease (from M0 to M1) where an additional 12% of cases were deemed M1 following PET-CT. CONCLUSIONS: PET-CT in high-grade bone and soft tissue sarcoma can add significant benefit to routine CT/MRI staging. Further prospective and multi-centre evaluation of PET-CT is warranted to determine the actual predictive value and cost-effectiveness of PET-CT in directing clinical management of clinically complex and heterogeneous high-grade sarcomas.

De novo donor-specific HLA antibodies after combined intestinal and vascularized composite allotransplantation - a retrospective study.

Combining vascularized composite allotransplantation (VCA) with intestinal transplantation to achieve primary abdominal closure has become a feasible procedure. Besides facilitating closure, the abdominal wall can be used to monitor intestinal rejection. As the inclusion of a VCA raises the possibility of an enhanced alloimmune response, we investigated the incidence and clinical effect of de novo donor-specific HLA antibodies (dnDSA) in a cohort of patients receiving an intestinal transplant with or without a VCA. The sequential clinical study includes 32 recipients of deceased donor intestinal and VCA transplants performed between 2008 and 2015; eight (25%) modified multivisceral transplants and 24 (75%) isolated small bowel transplants. A VCA was used in 18 (56.3%) cases. There were no episodes of intestinal rejection without VCA rejection. Fourteen patients (14 of 29; 48.3%) developed dnDSA. In the VCA group, fewer patients developed dnDSA; six of 16 (37.5%) VCA vs. eight of 13 (61.5%) non-VCA. There was no statistically significant difference in one- and 3-year overall graft survival stratified for the presence of dnDSA; P = 0.286. In the study, there is no evidence that the addition of a VCA increases the incidence of dnDSA formation compared to transplantation of the intestine alone.

Giant cell tumour of the distal radius/ulna: response to pre-operative treatment with short-term denosumab.

BACKGROUND: Treatment of giant cell tumour of bone (GCTB) of the distal radius/ulna poses a surgical challenge, as complex reconstructive surgery may be required. This study evaluates the clinical, radiological and pathological findings in five cases of GCTB of the distal forearm where a 3 month course of denosumab was given prior to surgery. METHODS: Patients with biopsy proven distal forearm GCTB, treated for 3 months with denosumab, followed by salvage surgery (curettage and cementation) were included. Wrist pain and function were assessed using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT were performed pre-treatment and 2 months after initiation of denosumab therapy. Histological comparison was made between the original biopsy and surgical curettage specimens. RESULTS: Five patients with an average age of 25 years were included in the study. Improvement in wrist pain and function was seen in all patients with the average MMWS increasing from 30 pre-treatment to 85 at 3 months. Plain radiographs demonstrated marginal sclerosis in all cases with reconstitution of cortical and subarticular bone by 2 months; internal matrix sclerosis and osseous consolidation was more variable. Increased tumour heterogeneity and low signal were observed on T2-weighted MR images. PET/CT revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2 months. Histology showed disappearance of osteoclasts and increased fibro-osseous tissue. Denosumab treatment has the potential to facilitate salvage surgery, thus avoiding bone resection and graft reconstruction. A good outcome was achieved apart from local recurrence in one case. Follow up ranged from 17 to 54 months. CONCLUSION: Distal forearm GCTB responds clinically, radiologically and histologically to a short course of pre-operative denosumab therapy, which has the potential to facilitate salvage surgery.