In a recent phase 2 superiority clinical trial we demonstrated that a single dose of 60mg of the human monoclonal antibody denosumab inhibits osteolytic lesion activity in patients undergoing revision total hip arthroplasty (THA), demonstrating proof of biological efficacy for this clinical application. Here, we examined the effect that denosumab has on disease biology at the osteolysis tissue level. Osteolytic tissue taken from the prosthesis-bone lesion interface at revision surgery in patients with osteolysis (n=10 participants that had received a single 60 mg dose of denosumab 8 weeks prior to revision surgery and n=10 that had received placebo) was examined for total genetic message activity and protein levels using whole genome sequencing and mass spectrometry, respectively. The top five upregulated enriched pathways with denosumab treatment included inflammatory response, myeloid cell activation, myeloid leukocyte migration, neutrophil and granulocyte activation (p<6.26 × 10. −28. ). Cell morphogenesis was amongst the most downregulated pathways (p<3.42 ×10. −23. ). Finally, comparison of the trial mRNA and protein data versus mouse single cell RNA sequencing data of the same pathway blockade in mouse tibia showed the same direction of effect, suggesting that giving the drug causes then cells responsible for osteolysis to disperse into a more immature form (128 of 189 genes (z=4.87, P<0.0001) disease and functional pathways at the mRNA level and 10 of 11 (z=2.72, P=0.0065) at the protein level). In this first-in-man study we identify multiple genes and pathways within periprosthetic osteolysis tissue that are affected by denosumab treatment. The dominant pathways involved upregulation of innate inflammatory signaling and downregulation of cell morphogenesis. We also found enrichment of similar disease and functional pathways at both the mRNA and protein levels versus mRNA pathway enrichment found in mouse osteomorphs. These data provide the first human data of the mechanistic effect of denosumab treatment on inflammatory osteolytic lesion activity after joint replacement that is necessary to support its clinical application. ∗Winner of The Bone & Joint Journal prize∗

Aims. Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review. Methods. We included 76 patients with distal radius GCTB in three sarcoma centres (1990 to 2019). Median follow-up was 8.8 years (2 to 23). Seven patients underwent curettage, 38 curettage with adjuvants, and 31 resection; 20 had denosumab. Results. Recurrence rate was 71% (5/7) after curettage, 32% (12/38) after curettage with adjuvants, and 6% (2/31) after resection. Median time to recurrence was 17 months (4 to 77). Recurrences were treated with curettage with adjuvants (11), resection (six), or curettage (two). Overall, 84% (38/45) was cured after one to thee intralesional procedures. Seven patients had 12 months neoadjuvant denosumab (5 to 15) and sixmonths adjuvant denosumab; two recurred (29%). Twelve patients had six months neoadjuvant denosumab (4 to 10); five recurred (42%). Two had pulmonary metastases (2.6%), both stable after denosumab. Complication rate was 18% (14/76, with 11 requiring surgery). At follow-up, median MusculoSkeletal Tumour Society score was 28 (18 to 30), median Short Form-36 Health Survey was 86 (41 to 95), and median Disability of Arm, Shoulder, and Hand was 7.8 (0 to 58). Conclusion. Distal radius GCTB treatment might deviate from general GCTB treatment because of complexity of wrist anatomy and function. Novel insights on surgical treatment are presented in this multicentre study and systematic review. Intralesional surgery resulted in high recurrence-rate for distal radius GCTB, also with additional denosumab. The large majority of patients however, were cured after repeated curettage. Cite this article: Bone Jt Open 2022;3(7):515–528

Abstract. Objective. In this phase 2 clinical trial (EudraCT 2011-000541-20) we examined the effect of denosumab versus placebo on osteolytic lesion activity in patients undergoing revision surgery after THA. Methods. Men and women ≥ 30 years old scheduled for revision surgery for symptomatic, radiologically-confirmed osteolysis were randomised (1:1) to receive either denosumab 60mg or placebo subcutaneously eight weeks prior to operation. At surgery, biopsies from the osteolytic membrane-bone interface were taken for histomorphometric analysis of osteoclast number, the primary outcome measure. Secondary outcome measures included other static histomorphometric indices and systemic bone turnover markers. Adverse events and patient-reported clinical outcome scores were recorded as safety endpoints. Results. Of the 24 subjects enrolled, 22 completed the study (10 denosumab) and comprise the per-protocol analysis. There were no differences in baseline characteristics and bone turnover markers between groups (p>0.05). The denosumab group had 78% fewer osteoclasts at osteolytic lesion sites (95% CI −61 to −95, P=0.011), 81% lower osteoclast surface (−70 to −95, P=0.009), and 73% lower eroded surface (−54 to −92, P=0.020) compared to the placebo group. Number of osteoblasts and osteoblast surface were also reduced by 81% (−62 to −100, p=0.021) and 82% (−64 to −101, p=0.017), respectively. Immunocytochemistry for cell proliferation (Ki67) and apoptosis (Caspase 3) identified no differences between the groups (p>0.05). At surgery, serum CTX-I in the denosumab group was 80% lower (−65 to −95, p<0.001), TRAP5b −65% (−40 to −90, p<0.001), PINP −53% (−41 to −65, p<0.001). Patient-reported outcome measures and the rate of adverse events (denosumab 6, placebo 7) were similar between groups (P>0.05). Conclusion. A single dose of denosumab reduced osteoclast activity within osteolytic lesions and was safe to administer. These data provide a biological basis for a phase 3 trial using clinical outcomes of pain, function and prosthesis survival as the study endpoints. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of pathological fractures in patients with bone metastases from advanced cancers by evaluating all available randomized controlled trials (RCTs) on this subject. A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing zoledronic acid with denosumab in prevention of pathological fractures in bone metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were pathological fractures. Four RCTs (7320 patients) were included. Denosumab was superior to ZA in reducing the likelihood of pathological fractures, when all tumour types were combined (OR 0.86, 95% CI [0.74, 0.99], p = 0.04). Denosumab was not significantly favoured over ZA in endodermal origin (breast and prostate) (OR 0.85, 95% CI [0.68, 1.05], p = 0.13) and mesodermal origin tumours (solid tumours and MM) (OR 0.87, 95% CI [0.71, 1.06], p = 0.16). Denosumab significantly reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases. When pathological fractures were grouped by tumour origin (endodermal or mesodermal), there was no significant difference between denosumab and ZA. Further long-term studies are needed to confirm the effectiveness of these treatment regimens

To date there is no medical treatment alternative to surgery for osteolysis after THA. In this proof-of-concept clinical trial we examined the effect of a human monoclonal antibody against osteoclasts versus placebo on osteolytic lesion activity in patients undergoing revision surgery. Patients scheduled for revision for symptomatic osteolysis were randomised (1:1) to receive either denosumab 60mg or placebo subcutaneously eight weeks prior to operation. At surgery, biopsies from the osteolytic membrane-bone interface were taken for histomorphometric analysis of osteoclast number. Secondary outcome measures included systemic bone turnover markers. 22 subjects completed the study (10 denosumab). The denosumab group had 83% (−63 to −97), P=0.011 fewer osteoclasts at osteolytic lesion sites, 87% lower osteoclast surface (−65 to −95, P=0.009), and 72% lower eroded surface (−35 to −93, P=0.020) versus the placebo group. At surgery, serum CTX-I, TRAP5b and PINP were 80% (−65 to −95, p<0.001), 57% (−40 to −90, p<0.001), and 44% (−41 to −65, p<0.001) lower in the denosumab versus placebo groups, respectively. The rate of adverse events (denosumab 6, placebo 7) were similar between groups (P>0.05). These data provide a biological basis for a definitive clinical trial using pain, function and prosthesis survival as the study endpoints. As osteolysis/ aseptic loosening is the leading cause of prosthesis failure world-wide, the establishment of a non-surgical solution would reduce patient suffering and dramatically reducing the cost to healthcare economies

Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy

Aim. The osteolytic process of osteomyelitis is, according to textbooks, caused by increased osteoclast activity due to RANKL production by osteoblasts. However, recent findings contradict this theory. Therefore, the aim was to investigate, in a porcine osteomyelitis model, how osteolysis is affected by massive inflammation and RANKL blocking, respectively. In parallel, patients with chronic osteomyelitis, diabetes, foot osteomyelitis, and fracture related infections (FRI) were included for advanced histological analysis of osteolysis. Methods. In pigs, a tibial implant cavity was created and inoculated with 10. 4. CFU of Staphylococcus aureus: Group A (n=7). Group B (n=7); + 1cm. 3. spongostan into the cavity. Group C (n=4); + systemic Denosumab treatment. Spongostan was used as an avascular material to support bacterial growth and thus increase the inflammatory response. Denosumab treatment was administrated to suppress osteoclast activity by RANKL inhibition (as in osteoporotic patients). The volume of osteolysis was accessed by CT scans. Immunohistochemistry with antibodies towards Cathepsin K was used to identify osteoclasts within the bone lesions. Briefly, the number of Cathepsin K positive cells, i.e., both precursors and bone resorbing osteoclasts, respectively, were counted in 10 high power fields (400x). In total, 50 bone infection patients were included (Herlev Hospital). From each patient five parried samples were taken for histology and microbiology, respectively. Histopathology, CT osteolysis volume estimation, and molecular expression of osteoclasts and inflammatory markers are ongoing. One FRI patient was osteoporotic and treated with Denosumab for 6 years. Results. All pigs were confirmed infected in the implant cavity. The volume (2.41 ± 1.29cm. 3. ) of osteolysis was significantly increased in the spongostan group in comparison to Group A (1.24 ± 0.59 cm. 3. ) (p=0.04). Thereby, the spongostan group had bacteria deeper into the bone from the inoculation point. Sufficient Denosumab treatment, i.e. reduced serum Ca was seen in 3 pigs. None of the Denosumab treated pigs showed reduced osteolysis in comparison to Group A (1.42 ± 0.63 cm. 3. ). The Cathepsin K score of Group C was 17 (15-23 IQR) of precursor osteoclasts and 2 (0-2 IQR) of osteoclasts in Howship lacunae. The Denosumab treated patient showed substantial osteolysis and histological analysis confirmed acute inflammatory. Conclusions. Application of spongostan, i.e., bacterial host optimization and massive inflammation promotes osteolysis and local bacterial dissemination. Osteoclast blocking with Denosumab showed no impact on osteolysis. Elucidation of the pathophysiology causing bone loss in osteomyelitis is fundamental. However, the widely accepted osteoclast-based theory might not be the only relevant

Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression. We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months). 109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation. Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs

The August 2015 Oncology Roundup. 360 . looks at: Glasgow prognostic score in soft-tissue sarcoma; Denosumab in giant cell tumour; Timing, complications and radiotherapy; Pigmented villonodular synovitis and arthroscopy; PATHFx: estimating survival in pathological cancer; Prosthetic lengthening of short stumps; Chondrosarcoma and pathological fracture

The June 2015 Oncology Roundup. 360 . looks at: Infection in megaprosthesis; Impressive results for mid femoral reconstruction; Revered teaching or old myth? Femoral neck protection in metastatic disease; Megaprosthesis about the knee; Malignant transformation in multiple hereditary exostoses; Fracture of intercalary bone allograft; Comorbidity and outcomes in sarcoma; A worrying turn? Use of denosumab for giant cell tumour of bone

The August 2014 Oncology Roundup. 360 . looks at: Anaesthesic modality does not affect outcomes in tumour surgery; infection predictors in orthopaedic oncology; sarcoma depth unimportant in survival; photon/proton radiotherapy surprisingly effective in chondrosarcoma control; total humerus replacement a success!; LDH simple predictor of survival in sarcoma; Denosumab again! and Oops procedures in triplicate

Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1

Introduction and Objective. Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. Other emerging treatments for ABCs include bisphosphonates, percutaneous doxycycline, sclerotherapy and Denosumab. In addition, we previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. One of the potential advantages of such a method is that surgical treatments are not necessary, thus allowing for both a minimally invasive approach and the treatment of poorly accessible lesions. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine and followed for at least one year. Materials and Methods. Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12– 60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. Results. Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48±2.36 HU to 161.71±23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up. We also observed that five out of six female patients (83.3%) were less than sixteen years old and four of these (66.7%) were managed with a single dose of BMC injection, while a higher percentage of male patients (6/8, 75%) were more than sixteen years old and more than one injection was administered to them. Conclusions. The results of this study reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE is contraindicated or ineffective. The initial size of the cyst and its localization does not influence the efficacy of the treatment. However, BMC injection could be indicated as treatment of choice for spinal ABC in young adolescent women

The October 2013 Oncology Roundup. 360 . looks at: En bloc resection, irradiation and re-implantation; Metastasis and osteosarcoma; Mobile spine and osteosarcoma; Denosumab miraculous for GCT; Fevers, megaprostheses and sarcomas; PET and prognosis; Canine sarcomas not so different?; Bone cement and giant cell tumours

Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Aims

Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis.

Aims

The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.