Journal of Bone Oncology最新文献

{"title":"The risk of pathological fractures after intralesional curettage in Atypical Cartilaginous Tumours: A retrospective cohort study","authors":"C.H.J. Scholte ,&nbsp;K. van Langevelde ,&nbsp;D.M.J. Dorleijn ,&nbsp;M. Fiocco ,&nbsp;D. Broekhuis ,&nbsp;P.D.S. Dijkstra ,&nbsp;M.A.J. van de Sande ,&nbsp;R.J.P. van der Wal","doi":"10.1016/j.jbo.2025.100731","DOIUrl":"10.1016/j.jbo.2025.100731","url":null,"abstract":"<div><h3>Purpose</h3><div>Atypical cartilaginous tumors (ACT) are locally aggressive, cartilage-producing neoplasms, traditionally classified as chondrosarcoma grade 1. They exist within the spectrum of cartilaginous tumors, between enchondroma and high-grade chondrosarcoma. The diagnosis of ACT remains challenging, with limited consensus on optimal treatment. Despite ongoing debate, intralesional curettage is commonly performed, though the risk of pathological fractures post-treatment remains a significant complication. This study aims to investigate the impact of cortical window design on fracture risk following curettage for ACT in the distal femur.</div></div><div><h3>Methods</h3><div>We compared two types of cortical windows: smooth oval (low stress riser) and windows with sharp or predrilled rounded corners (high stress riser). A retrospective cohort of 153 patients treated between 2000 and 2020 was included. Fracture occurrence was recorded, and logistic regression models were used to assess the relationship between surgical technique and fracture risk. We corrected for void filling and tumour size.</div></div><div><h3>Results</h3><div>Our findings revealed no significant difference in fracture risk between the two types of cortical windows (OR = 1.62, 95 % CI:0.66–3.96). However, the use of cement as a void filler significantly increased fracture risk, with odds ratio (OR) approximately five times higher than those using bone chips (OR = 5.00, 95 % CI:1.81–13.88). Tumor size (cm) was also associated with fracture risk (OR 1.31, 95 % CI:1.04–1.63).</div></div><div><h3>Conclusion</h3><div>The study highlights the importance of choosing appropriate void filling material, with bone chips offering a lower fracture risk compared to cement. These results suggest that optimizing surgical techniques, particularly the choice of filling material, may reduce post-curettage fracture risk in ACT treatment.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100731"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WGCNA-identified COL13A1 drives osteosarcoma metastasis and progression via TGF-β signaling","authors":"Kang-Wen Xiao ,&nbsp;Zhenyi Chen ,&nbsp;Chong Zhang ,&nbsp;Zhiqiang Yang ,&nbsp;Liangyu Guo ,&nbsp;Yuanlong Xie ,&nbsp;Jun Lei ,&nbsp;Lin Cai","doi":"10.1016/j.jbo.2025.100721","DOIUrl":"10.1016/j.jbo.2025.100721","url":null,"abstract":"<div><div>Osteosarcoma (OS) is a malignant bone tumor with high incidence of metastasis. However, the molecular landscape of osteosarcoma remains incompletely understood. Weighted gene co-expression network analysis (WGCNA), differential expressed genes (DEGs), Cox regression, gene set enrichment analysis (GSEA), receiver operating characteristic curve (ROC) and survival analysis were conducted to screen potential targets and molecular mechanism for OS. Seven modules were considered to be closely related to the prognosis of OS. Subsequent immunohistochemistry (IHC), survival and ROC analysis indicated that high expression of COL13A1 was seen in OS tissue and was significantly associated with poor clinical outcome. COL13A1 expression may correlate with inhibition of M1 polarization and could serve as a predictor for immunotherapy response. Further cellular experiments showed that the expression of COL13A1 promoted the proliferation, migration and invasion. Besides, high expression of COL13A1 enhanced TGF-β signaling through β1 integrin and upregulated MMP9 and cyclin D1 expression. Finally, the low expression of COL13A1 limited the weight and lung metastasis of tumor, and reduced bone destruction in the orthotopic tumor-bearing model. COL13A1 was identified as a novel regulator of OS progression via TGF-β signaling, suggesting its potential as a therapeutic target pending further validation.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100721"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of bone architecture following androgen deprivation therapy in patients with prostate cancer using 3D-modeling from hip DXA","authors":"Ji Yong Park ,&nbsp;A Ram Hong ,&nbsp;Jee Hee Yoon ,&nbsp;Hee Kyung Kim ,&nbsp;Ho-Cheol Kang ,&nbsp;Seung Il Jung ,&nbsp;Dongdeuk Kwon ,&nbsp;Eu Chang Hwang","doi":"10.1016/j.jbo.2025.100713","DOIUrl":"10.1016/j.jbo.2025.100713","url":null,"abstract":"<div><h3>Introduction</h3><div>Androgen deprivation therapy (ADT) for prostate cancer negatively affect areal bone mineral density (aBMD); however, its impact on volumetric BMD (vBMD) and bone geometry remains underexplored. This study aimed to evaluate changes in aBMD, vBMD, and hip structural analysis (HSA) following one year of ADT.</div></div><div><h3>Materials and methods</h3><div>This retrospective observational study included 41 patients with prostate cancer without bone metastasis who received ADT for one year and underwent dual-energy X-ray absorptiometry (DXA) both before and after treatment. In addition to aBMD, trabecular and cortical vBMD, integral vBMD (trabecular + cortical), cortical surface BMD (sBMD), cortical thickness, and hip structural parameters were assessed at the hip using 3D-Shaper software.</div></div><div><h3>Results</h3><div>The mean age and body mass index of the patients were 75.5 ± 6.8 years and 24.0 ± 3.0 kg/m², respectively. More than half had a Gleason score of 4 or 5, and the majority had T3 disease. After one year of ADT, significant reductions in aBMD were observed at the lumbar spine (–4.5 ± 4.0 %, <em>P</em> &lt; 0.001) and total hip (–3.7 ± 5.1 %, <em>P</em> &lt; 0.001). 3D-DXA analysis revealed significant declines in integral vBMD (–3.8 ± 3.9 %) and trabecular vBMD (–4.9 ± 7.4 %) (both <em>P</em> &lt; 0.001), while cortical vBMD showed no significant change (–1.6 ± 6.0 %, <em>P</em> = 0.062) at the total hip. Cortical sBMD decreased significantly by –2.7 ± 5.2 % (<em>P</em> &lt; 0.001). Cortical thickness also significantly decreased at the total hip (–1.2 ± 3.2 %, <em>P</em> = 0.011). With respect to hip structural parameters, cross-sectional area consistently decreased, and buckling ratio increased across the femoral neck, trochanteric, and shaft regions (all <em>P</em> &lt; 0.05), indicating increased femoral fragility and reduced resistance to axial and compressive forces.</div></div><div><h3>Conclusions</h3><div>ADT exerts a substantial detrimental effect on bone strength, resulting in reductions in aBMD, vBMD, and alteration of HSA. 3D-DXA may serve as a valuable and accessible tool for detecting structural bone changes in prostate cancer patients undergoing ADT.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100713"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rotationplasty performed in adults versus minors: a comparative study of long-term quality of life, functional and biomechanical outcomes","authors":"Gitte G.J. Krebbekx ,&nbsp;N.F.J. Waterval ,&nbsp;M.A. Brehm ,&nbsp;M.J.C. Duivenvoorden ,&nbsp;I.N. Sierevelt ,&nbsp;J.A.M. Bramer ,&nbsp;G.M.M.J. Kerkhoffs ,&nbsp;F.G.M. Verspoor","doi":"10.1016/j.jbo.2025.100732","DOIUrl":"10.1016/j.jbo.2025.100732","url":null,"abstract":"<div><h3>Background</h3><div>Rotationplasty is a surgical technique primarily used in pediatric patients with malignant bone tumors around the knee. Its application in adults is rare, and outcomes are poorly defined. This study aimed to compare long-term QoL, function, and gait between patients treated with rotationplasty in childhood versus adulthood.</div></div><div><h3>Methods</h3><div>This cross-sectional post-hoc predefined secondary analysis included 33 patients treated between 1980–2002 (9 adults, 24 minors). Assessments included the mental and physical component score of the Short Form-36 (SF-36, MCS/ PCS), overall satisfaction, radiographs (Kellgren-Lawrence) of the pseudo-knee, contralateral ankle, and hips, Toronto Extremity Salvage Score (TESS), Musculoskeletal Tumor Society Score (MSTS), energy cost of comfortable walking during a 6-minute walk test, and 3-Dimenional gait analysis. Group comparisons were performed across all outcomes. Additionally, a systematic literature search identified published adult cases.</div></div><div><h3>Results</h3><div>People who underwent surgery during adulthood reported significantly higher physical QoL compared to those operated in childhood (MD 6.1, 95 % CI 0.0–12.3; <em>p</em> = 0.05). No significant differences were observed for the SF-36 MCS, TESS, MSTS, energy cost, sagittal-plane biomechanics, and radiographic OA prevalence. Adults exhibited a significantly shorter stride length (p &lt; 0.01) and a longer double support phase (p = 0.01) compared to those treated in childhood. The literature review (22 studies, 51 patients) demonstrated overall favorable outcomes, though no objective gait data were reported.</div></div><div><h3>Conclusion</h3><div>Adults who undergo rotationplasty can achieve long-term quality of life, functional, and gait outcomes at least comparable to those operated on in childhood. These findings suggest that rotationplasty may be a viable reconstructive option in adults.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100732"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis","authors":"Guofang Huang ,&nbsp;Tianhui Hou ,&nbsp;Dianwen Song ,&nbsp;Tong Meng","doi":"10.1016/j.jbo.2025.100729","DOIUrl":"10.1016/j.jbo.2025.100729","url":null,"abstract":"<div><div>Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME—a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune cells, extracellular matrix, and bioactive factors (e.g., cytokines, growth factors)—orchestrates skeletal homeostasis physiologically, yet its dysregulation drives tumorigenesis and metastatic colonization via three interconnected axes: (1)<!--> <!-->Cellular dynamics<!--> <!-->(osteocyte senescence, immune evasion); (2)<!--> <!-->Matrix remodeling<!--> <!-->(imbalance between osteolytic and osteoblastic activity); (3)<!--> <!-->Signaling disruption<!--> <!-->(abnormal cytokine and growth factor signaling). While BME-directed therapies (e.g., receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, C-X-C chemokine receptor type 4(CXCR4) antagonists) show promise in disrupting tumor-supportive niches, their off-target effects on healthy bone (e.g., osteonecrosis, impaired fracture healing) pose significant clinical challenges. This review systematically synthesizes: BME composition and tumor-induced reprogramming, Mechanistic roles in metastasis and treatment resistance, Emerging targeted therapies and translational trade-offs. By positioning the BME as both a pathogenic driver and therapeutic vulnerability, we aim to inform future strategies for tissue-specific microenvironmental targeting in bone malignancies.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100729"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutting edge developments in bone oncology – Highlights from the Cancer and Bone Society 2024 annual meeting","authors":"Deanna N. Edwards ,&nbsp;Shreya Patel ,&nbsp;Gabriel M. Pagnotti","doi":"10.1016/j.jbo.2025.100724","DOIUrl":"10.1016/j.jbo.2025.100724","url":null,"abstract":"<div><div>The 2024 Annual Conference of the Cancer and Bone Society (CABS), held jointly with the Bone Research Society at the University of Sheffield, highlighted the Society’s enduring mission to advance understanding of cancer–bone interactions through collaboration, mentorship, and scientific excellence. Established from the early Cancer Induced Bone Disease meetings and re-emerging as an independent body in 2016, CABS continues to serve as a global community bridging basic, translational, and clinical research. This year’s meeting featured a comprehensive scientific program spanning tumor–bone biology, therapeutic innovation, and microenvironmental regulation. Clinical sessions emphasized the evolution of bone-targeted treatments such as bisphosphonates, denosumab, and radiopharmaceuticals, alongside predictive biomarkers to guide personalized care. Presentations on renal cell carcinoma bone metastases, multiple myeloma, and prostate cancer underscored persistent clinical challenges and opportunities for integration of immunotherapies and precision radiotherapy. Molecular sessions revealed how non-coding RNAs, TGF-β/Gli2 signaling, metabolic dependencies, and stromal mediators—including osteomodulin, IL-1β, and adiponectin—govern tumor colonization, dormancy, and resistance. Advances in immuno-oncology demonstrated the potential of γδ CAR-T cells, oncolytic viruses, and immune-metabolic targeting to enhance therapeutic efficacy in the bone microenvironment. Spatial and single-cell profiling provided unprecedented resolution of the metastatic niche, identifying novel osteoblast-derived stromal subsets and neurovascular remodeling as key determinants of disease progression. Complementary preclinical models and computational simulations, including 3D engineered bone marrow constructs and micro–finite element analysis, offered new frameworks to study therapeutic responses and fracture risk. The meeting also celebrated the growing leadership of Early-Stage Investigators (ESIs), whose contributions extended beyond research presentations to creative networking and mentorship events. These efforts reflected CABS’ commitment to inclusivity, community building, and sustaining the next generation of leaders in cancer and bone research. Collectively, the 2024 CABS Annual Conference captured a transformative moment in the field—where mechanistic discoveries, advanced modeling, and translational collaboration converge to improve outcomes for patients with skeletal malignancies. As CABS looks ahead to the 2026 meeting in Tampa, Florida, the Society remains steadfast in fostering global partnerships and advancing integrative approaches to conquer cancer in bone.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100724"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone metastasis in colorectal cancer: Pathophysiology, prognostic factors, survival outcomes, and treatment strategies – A comprehensive review","authors":"Lea Hatoum ,&nbsp;Rita El Murr ,&nbsp;Ahmad Assi ,&nbsp;Rami Mohanna ,&nbsp;Amer Sebaaly ,&nbsp;Hampig-Raphaël Kourie","doi":"10.1016/j.jbo.2025.100727","DOIUrl":"10.1016/j.jbo.2025.100727","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer ranks as the third most prevalent cancer globally, with over 1.9 million new cases and 930,000 deaths in 2020. While the liver and lungs are the most common site of colorectal cancer metastases, bone metastasis is relatively rare but clinically significant. The rarity of bone metastasis in colorectal cancer, early diagnosis challenges, and the poorly understood mechanisms underlying bone metastasis have resulted in lesser research compared to other metastatic sites of colorectal cancer.</div></div><div><h3>Objective</h3><div>The goal of this review is to summarize pathophysiology, clinical presentation, risk and prognostic factors, survival outcomes, and treatment options for bone metastasis in colorectal cancer. Results: Bone metastasis occurred in 6 to 10 % of colorectal cancer patients, with the spine and pelvis being the most common sites. Bone metastasis from colorectal cancer may result from hematogenous dissemination and retrograde venous flow through Batson’s plexus. Early diagnosis can be challenging, and Positron Emission Tomography / Computed Tomography (PET/CT) provided the best accuracy for diagnosing bone metastasis in colorectal cancer. Isolated bone metastasis, low neutrophil-to-lymphocyte ratio (NLR) (high NLR with HR: 1.54), low alkaline phosphatase levels, N0 stage colorectal cancer were associated with a better prognosis and survival. High carcinoembryonic antigen (OR: 2.368, HR: 3.300), alkaline phosphatase (OR: 6.89, HR: 2.12), and CA 19–9 levels (HR: 1.5), Lactate dehydrogenase (HR: 1.961), perineural invasion (HR: 3.457), right sided location (HR: 1.84), multiples bone metastasis sites (HR: 1.452), hypercalcemia (HR: 3.75), pathologic fracture (HR:1.91) and more than two extra-bone metastatic organs (HR: 2.357) were linked to worse prognosis. The therapeutic approach for colorectal cancer patients with bone metastasis consists of a multidisciplinary strategy including systemic chemotherapy, palliative surgery, radiotherapy and bisphosphonate.</div></div><div><h3>Conclusion</h3><div>Early diagnosis and management of bone metastasis in colorectal cancer patients is essential to improve quality of life and survival. Further research is needed to identify methods for early detection and develop tailored treatment strategies.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100727"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic kidney disease and denosumab in metastatic bone disease: A multicenter Turkish cohort study on severe hypocalcemia, skeletal events, and survival","authors":"Halil İbrahim Ellez ,&nbsp;Hüseyin Salih Semiz ,&nbsp;Ferhat Ekinci ,&nbsp;Atike Pınar Erdoğan ,&nbsp;Fatih Kuş ,&nbsp;Fatih Karataş ,&nbsp;Ertuğrul Bayram ,&nbsp;Kubilay Karaboyun ,&nbsp;Havva Yeşil Çınkır ,&nbsp;Nilgün Yıldırım ,&nbsp;Melek Karakurt Eryılmaz ,&nbsp;Esma Türkmen Bekmez ,&nbsp;Özkan Alan ,&nbsp;Melike Özçelik ,&nbsp;Yakup Düzköprü ,&nbsp;Teoman Şakalar ,&nbsp;Naziye Ak ,&nbsp;Yusuf İlhan ,&nbsp;Tuğba Yavuzşen ,&nbsp;Nazım Serdar Turhal","doi":"10.1016/j.jbo.2025.100730","DOIUrl":"10.1016/j.jbo.2025.100730","url":null,"abstract":"<div><h3>Background</h3><div>Denosumab, a monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), is widely used to prevent skeletal-related events (SREs) in patients with bone metastases from solid tumours. However, its safety in individuals with advanced chronic kidney disease (CKD), particularly regarding severe hypocalcaemia and skeletal complications, is not well defined.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, multicentre study within the Turkish Oncology Group including patients with breast, prostate, or lung cancer who received denosumab between January 2011 and December 2022. Demographic and clinical data, CKD stage, prior fractures, serum calcium levels, episodes of hypocalcaemia, concomitant medications, and adverse events were recorded. Primary endpoints were the incidences of grade ≥ 3 hypocalcaemia and other grade ≥ 3 toxicities; secondary endpoints included skeletal-related events and overall survival.</div></div><div><h3>Results</h3><div>We analysed 264 patients from 17 oncology centres. Overall, 18 patients (6.8 %) experienced grade ≥ 3 toxicity, including 16 cases of severe hypocalcaemia and two of renal function decline. Among 42 patients with baseline estimated glomerular filtration rate (eGFR) &lt; 60 mL/min, 13 (31.0 %) developed grade ≥ 3 toxicity (11 hypocalcaemia, two renal decline), representing a significantly higher risk than in patients with eGFR ≥ 60 mL/min (p &lt; 0.01). Pathological fractures occurred in 21 patients, six with eGFR &lt; 60 mL/min (p = 0.035). Eight patients required surgery for skeletal-related events, four with eGFR &lt; 60 mL/min (p = 0.012).</div></div><div><h3>Conclusion</h3><div>Cancer patients with CKD receiving denosumab have an increased risk of severe hypocalcaemia and skeletal complications. Close monitoring of calcium and renal function is essential, and clinicians should carefully balance the benefits of denosumab against these risks in this vulnerable population.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100730"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient increase in skeletal-related events after discontinuation of high-dose denosumab in cancer patients","authors":"Nokitaka Setsu ,&nbsp;Nobuhiko Yokoyama ,&nbsp;Taito Esaki ,&nbsp;Masafumi Yamaguchi ,&nbsp;Eriko Tokunaga ,&nbsp;Takahito Negishi","doi":"10.1016/j.jbo.2025.100717","DOIUrl":"10.1016/j.jbo.2025.100717","url":null,"abstract":"<div><h3>Background</h3><div>Denosumab is widely used to prevent skeletal-related events (SREs) in patients with bone metastases. However, rebound bone resorption after discontinuation is recognized. In osteoporosis, discontinuation of low-dose denosumab increases multiple vertebral fractures, but data on high-dose discontinuation remain limited.</div></div><div><h3>Methods</h3><div>Among 493 patients treated with high-dose denosumab at our institution (2014–2023), 78 met eligibility criteria. SREs during and after treatment were compared using each patient as their own control. SREs were defined as pathological fracture, spinal cord compression, or radiotherapy/surgery for metastatic bone pain. Hypercalcemia, benign fragility fractures, and serum ALP level were also assessed.</div></div><div><h3>Results</h3><div>A total of 11 SREs were observed during denosumab and 24 after discontinuation. Post-discontinuation incidence was 14.1 per 1,000 person-months, 3.3 times higher than during treatment (95 % CI, 1.4–7.8). The increase was significant at 6–15 months, peaking at 12–15 months (IRR 8.7, 95 % CI, 2.8–27.5), and declined thereafter. Fewer denosumab doses were also associated with a higher risk of SREs after discontinuation. Two benign fragility fractures occurred during denosumab and four after discontinuation. Grade ≥ 3 hypercalcemia occurred only after discontinuation (3 cases). Transient ALP elevation at 9–18 months was observed in patients with post-discontinuation SREs, and ALP ≥ 95 U/L at 6 months predicted subsequent SREs (AUC 0.80).</div></div><div><h3>Conclusion</h3><div>SREs increased significantly 6–15 months after high-dose denosumab discontinuation. Elevated ALP was associated with post-discontinuation SREs. These findings emphasize that discontinuation contributes to SRE risk, possibly via rebound bone resorption, and underscore the importance of continuation of therapy whenever possible.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100717"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Zimmer® segmental distal femur mega-prostheses: Patient survival, surgical outcomes and functional outcome","authors":"Christina Enciso Holm,&nbsp;Jesper Peter Bömers,&nbsp;Allan Villadsen,&nbsp;Michael Mørk Petersen","doi":"10.1016/j.jbo.2025.100722","DOIUrl":"10.1016/j.jbo.2025.100722","url":null,"abstract":"<div><h3>Background</h3><div>Modular knee mega-prostheses are considered the method of choice for reconstruction after resection of malignant bone lesions around the knee. The available literature evaluating Zimmer® Segmental mega-prostheses is sparse. The purpose of the present study is to evaluate the use of Zimmer® Segmental mega-prosthesis for reconstruction of the distal femur, following the resection of bone malignancies and aggressive benign bone tumors.</div></div><div><h3>Material and Methods</h3><div>A retrospective study including 59 consecutive patients (F/M = 35/24), mean age 58 (range 17–86) who underwent reconstructions of the distal femur due to malignant bone lesions (n = 51) or aggressive benign bone tumors (n = 8) from 2017 to 2022. All reconstructions were performed with the most recent Zimmer® Segmental System with the XT Distal Femoral Component. Kaplan-Meier survival analysis was used for evaluation of overall survival. Competing risk analysis was used for assessing cumulative incidence of revision and amputation. Patients were followed until death or end of study (December 31st, 2024). Functional outcome and quality of life was evaluated with Musculoskeletal Tumor Society Score (MSTS), European quality of life − 5 Dimensions score (EQ 5D) and Oxford Knee Score (OKS).</div></div><div><h3>Results</h3><div>Twenty-eight (n = 28) patients were alive at follow-up. Overall survival after 5-year was 44 % (CI95%: 30–58 %). The risk of implant failure after 1 and 5 years was 8 % (95 %CI 1–16 %) and 12 % (95 %CI 4–20 %) respectively. One patient (2 %) underwent amputation. Mean MSTS score was 17 (57 %) (range 3–30). Mean EQ 5D index score was 0.88 and mean EQ-5D VAS score was 68. OKS demonstrated a mean score of 31.</div></div><div><h3>Conclusion</h3><div>The Zimmer® Segmental mega-prosthesis in distal femur reconstruction with the improved XT femoral component, demonstrated a relatively low risk of implant failure, and a low risk of amputation. The risk of implant failure was higher among patients who underwent radiotherapy.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100722"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}