UNASSIGNED: The management of the GCT continues to be controversial. The most accepted treatment reported is extended curettage with various adjuvants. However, the rate of recurrence has been very high (10-66%). For better understanding of the lesion and its management, it has become necessary to revise the existing grading system.
UNASSIGNED: The recommendation of the proposed grading is based on 480 cases of GCT along with the analysis of other major reports published. Out of these, 279 were grade-II and 109 grade-III which were subjected to en bloc excision and reconstruction with non-vascularized fibular graft. Depending on the site, the grafts were stabilized with a suitable plate or extra long Kirschner wires.
UNASSIGNED: The observations made in 480 cases over a period of 5 decades revealed that for Campanacci grade-II and grade-III lesions, en bloc excision and suitable reconstruction resulted in minimum recurrence rate of 1.2%. The fibular reconstruction after excision has proved advantageous to our patients as it provides a stable joint in the form of an arthrodesis of the neighboring joint.
UNASSIGNED: GCT of bone has been a challenging lesion. Extended curettage has been recommended as the choice of treatment but the reported rate of recurrence has been high. En bloc excision and suitable reconstruction with fibular strut graft have resulted in 1.2% recurrence. It is, therefore, suggested the existing grading system should be revised mainly for grade-II and grade-III lesions which can bring down the high rate of recurrence in this unpredictable tumor.
UNASSIGNED: Level-IV.

Giant cell tumour of bone (GCTB) is one of the most common local aggressive tumourous lesions with a wide variety of biological behaviour. However, there are no clear indicative criteria when choosing the type of procedure and the complication rates remain high, especially in terms of local recurrence. The purpose of the study was to (1) identify the main risk factors for local recurrence, (2) evaluate the recurrence-free survival in dependence on neoadjuvant denosumab use and the type of procedure, and (3) compare the functional outcomes after curettage and en bloc resection. The group included 102 patients with GCTB treated between 2006 and 2020. The mean age of patients was 34.4 years (15-79). The follow-up period was 8.32 years (2-16) on average. Local recurrence occurred in 14 patients (29.8%) who underwent curettage and in 5 patients (10.6%) after en bloc resection. Curettage was shown to be a factor in increasing recurrence rates (OR = 3.64 [95% CI: 1.19-11.15]; p = 0.023). Tibial location was an independent risk factor for local recurrence regardless of the type of surgery (OR = 3.22 [95% CI: 1.09-9.48]; p = 0.026). The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments at five years postoperatively (p = 0.0307). Functional ability and pain as reported by patients at the latest follow-up were superior after curettage compared to resection for upper and lower extremity (mean difference: -4.00 [95% CI: -6.81 to -1.18]; p < 0.001 and mean difference: -5.36 [95% CI: -3.74 to -6.97]; p < 0.001, respectively). Proximal tibia tumour location and curettage were shown to be major risk factors for local recurrence in GCTB regardless of neoadjuvant denosumab treatment. The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments. The functional outcome of patients after curettage was better compared to en bloc resection.

BACKGROUND: Serum tartrate-resistant acid phosphatase 5b is well known to be increased in giant cell tumors of bone. However, there are only a few studies that analyzed the association with tartrate-resistant acid phosphatase 5b expression in those patients. Therefore, we analyzed the characteristics of patients with giant cell tumors of bone and high tartrate-resistant acid phosphatase 5b expression.
METHODS: This retrospective study included 26 patients with giant cell tumors of bone. The correlation between tartrate-resistant acid phosphatase 5b before initial treatment and tumor volume was evaluated. Patients were divided into two groups according to tartrate-resistant acid phosphatase 5b level. Statistical analysis was performed between the two groups.
RESULTS: Tartrate-resistant acid phosphatase 5b was elevated in 17/26 patients, and the mean value was 852 mU/dL. There was no correlation with tumor volume (r = 0.034, P = 0.86). The mean age of 34.5 years in the HT group was significantly younger than the mean age of 47.4 years in the LT group (P = 0.040). Pathologically, 19/26 cases showed at least one focal area with features of typical giant cell tumor of bone. Although 11/18 patients in the LT group exhibited relatively noticeable secondary changes, all patients in the HT group exhibited typical features (P = 0.0074).
CONCLUSIONS: Tartrate-resistant acid phosphatase 5b levels were not elevated in some giant cell tumors of bone. This study suggested that tartrate-resistant acid phosphatase 5b may be elevated in younger patients and in cases with fewer pathological secondary changes, regardless of tumor volume.

Understanding the genetic basis responding to nitrogen (N) fertilization in crop production is a long-standing research topic in plant breeding and genetics. Albeit years of continuous efforts, the genetic architecture parameters, such as heritability, polygenicity, and mode of selection, underlying the N responses in maize remain largely unclear. In this study, about n = 230 maize inbred lines were phenotyped under high N (HN) and low N (LN) conditions for 2 consecutive years to obtain 6 yield-related traits. Heritability analyses suggested that traits highly responsive to N treatments were less heritable. Using publicly available SNP genotypes, the genome-wide association study (GWAS) was conducted to identify n = 237 and n = 130 trait-associated loci under HN and LN conditions, n = 164 for N-responsive (NR) traits, and n = 31 for genotype by N interaction (G × N). Furthermore, genome-wide complex trait Bayesian (GCTB) analysis, a method complementary to GWAS, was performed to estimate genetic parameters, including genetic polygenicity and the mode of selection (S). GCTB results suggested that the NR value of a yield component trait was highly polygenic and that 4 NR traits exhibited negative correlations between SNP effects and their minor allele frequencies (or the S value <0)-a pattern consistent with negative selection to purge deleterious alleles. This study reveals the complex genetic architecture underlying N responses for yield-related traits and provides candidate genetic loci for N resilient maize improvement.

UNASSIGNED: Giant-cell tumor of bone (GCTB) is a relatively benign, but locally aggressive osteoclastogenic stromal tumour of the bone. Although denosumab has been approved as an monoclonal antibody against RANK ligand for the treatment of GCTB, few clinical trials of the benefit in tumor response have been conducted to prove the efficiency in Chinese population.
UNASSIGNED: In this multicentric, random controlled, clinical trial, 160 patients were enrolled to compare the therapeutic efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable GCTB.
UNASSIGNED: Between 2nd Jan 2015 and 1st Jan 2018, 160 adults (aged ≥ 18 years) with ①surgically unsalvageable GCTB, ②surgically salvageable GCTB with planned surgery expected to result in severe morbidity were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg once every 4 weeks with loading doses of 120 mg subcutaneously admininstered on days 8 and 15; n = 80) or intravenous zoledronic acid (ZA group; 4 mg once every 4 weeks; n = 80) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals.
UNASSIGNED: Denosumab and zoledronic acid had similar tumor responses (p = 0.118) and clinical benefits (p = 0.574). Disease progression was observed in fewer patients in the DB group (12.5%) than ZA group (15.0%). Denosumab caused fatigue (p = 0.001) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.059) and hypotension (p = 0.059). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was the same for the ZA group and the DB group (p = 0.425). The accumulate recurrence-free survival rate at 4-year follow-up is higher in DB group (p = 0.035).
UNASSIGNED: Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable GCTB.

(1) Despite the benign nature of the giant cell tumor of bone (GCTB), it shows a local recurrence rate of up to 50% and a chance of malignant transformation. The widely accepted local therapy in extremity GCTB is surgery, in the form of extended intralesional curettage with adequate disease clearance and retention of the limb, wherever possible. Denosumab, a human monoclonal antibody directed against the RANKL and associated inhibition of the RANKL pathway, is a relevant therapy option for advanced GCTB, to benefit tumor response and surgical down-staging. (2) The literature review of patients with GCTB treated with denosumab is performed via PubMed, using suitable keywords from January 2009 to January 2021. (3) Current indications for denosumab use are not definitively clear and unambiguous. Most GCTB patients with localized disease can be successfully treated with surgical curettage, and the role of denosumab in preoperative therapy in this patient population remains unclear. (4) However, patients with primary unresectable lesions or metastases may experience long-term clinical and radiological remission and pain control with denosumab treatment, and in this clinical situation, denosumab is currently the treatment of choice.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor commonly arising from the epiphysis of the distal femur and proximal tibia. Standard GCTB treatment is joint-preserving surgery performed using thorough curettage and the filling of the cavity with allo-, auto-, polymethyl methacrylate (PMMA), or synthetic bone graft. Calcium phosphate cement (CPC) is an artificial bone substitute, which has the benefit of being able to adjust defects, consequently inducing immediate mechanical strength, and promoting biological healing. Secondary osteoarthritis may occur following GCTB treatment and may need additional surgery if severe. However, details regarding surgery for secondary osteoarthritis have not been fully elucidated. There are no reports on the use of total knee arthroplasty (TKA) for the treatment of secondary osteoarthritis following CPC packing. The insertion of an alignment rod is a standard procedure in TKA; however, it was difficult to perform in this case due to CPC. Therefore, we used a computed tomography (CT)-free navigation system to assist the distal femur cut. This study presents a knee joint secondary osteoarthritis case following CPC packing for GCTB curettage that was treated with standard TKA.
METHODS: A 67-year-old Japanese woman, who was previously diagnosed with left distal femur GCTB and was treated by curettage and CPC packing 7 years ago, complained of severe knee pain. Left knee joint plain radiography revealed Kellgren and Lawrence (K-L) grade 4 osteoarthritis without evidence of tumor recurrence. Therefore, she was scheduled for TKA. There are no reports on the cutting of a femoral condyle surface with massive CPC with accurate alignment. Because it is difficult to insert the alignment rod intramedullary and cut the femoral condyle with CPC, we planned CT-free navigation-guided surgery for accurate bone cutting using an oscillating tip saw system to prevent CPC cracks. We performed standard TKA without complications, as planned. Postoperative X-ray showed normal alignment. Knee Society Knee Score (KSKS) and Knee Society Function Score (KSFS) ameliorated from 27 and 29 to 64 and 68, respectively The patient can walk without a cane postoperatively.
CONCLUSIONS: There was no report about the surface TKA guided by CT-free navigation after primary GCT surgery with CPC. We believe that this case report will help in planning salvage surgery for secondary osteoarthritis after CPC packing.

BACKGROUND: Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage.
METHODS: One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB.
CONCLUSIONS: Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.

To highlight the new developments in the management of advanced giant cell tumor of bone, a rare locally aggressive benign tumor, which was traditionally managed with surgery alone by either curettage and local adjuvant therapy, wide resection, or marginal excision. Here, we review the current role of systemic therapy for management of locally advanced or metastatic giant cell tumor of bone (GCTB).
The elucidation of the pathophysiology of giant cell tumor of bone, especially with regards to the role of nuclear factor kappa B ligand (RANKL), has led to the Food and Drug Administration (FDA) approval of denosumab in the management of locally advanced or metastatic GCTB. For advanced giant cell tumor where surgical resection alone can cause severe morbidity, the paradigm has shifted from local treatment alone to multidisciplinary management with the consideration of use of denosumab.

Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone. While the role of denosumab in the setting of advanced and unresectable disease is well established, its role in surgically resectable disease is currently under discussion. Several prospective and retrospective series on neoadjuvant therapy in potentially resectable tumor with high morbidity surgery reported a relapse rate of 10-20% after resection and 30-40% after curettage. At the same time, less morbid surgery has obvious clinical advantages for the patient, and several studies have shown the efficacy of denosumab in downgrading of the surgical procedure. Currently, the role of neoadjuvant denosumab in operable GCTB is limited to selected cases in which a diffuse reactive bone formation and peripheral ossification can make an easier surgical procedure, for example, in tumors with a large soft tissue component. A planned resection may become less morbid when preoperative denosumab is administered. Whenever a segmental resection is thought to be indicated at diagnosis, denosumab may be considered in the neoadjuvant setting. A preoperative course of 6 months is considered safe and effective. Two case scenarios are presented and critically discussed. Because of the high recurrence rates after denosumab treatment followed by curettage, we discourage the use of denosumab when curettage is considered feasible. In this setting, a short course of preoperative denosumab (2-6 months) may be considered for highly selected cases, for example in pathological fractures. The role of adjuvant denosumab needs further investigation. Long-term disease control has been reported in case of non-surgical lesions, even after treatment interruption, but there is no consensus on ideal treatment duration and dosage for these scenarios. In all cases, multidisciplinary discussion with oncology, pathologist, radiologist, and surgeons is mandatory. Patient\'s comorbidities, dental conditions, and preferences, including family planning, should always be taken into account.