Denosumab Re-Challenge and Long-Term Efficacy for Aneurysmal Bone Cyst of the Spine: Enhanced Treatment Algorithm.
Journal of clinical medicine
Surgical treatment of aneurysmal bone cysts (ABCs) can be challenging, especially in the spine. Non-surgical treatments such as with denosumab have shown promising results in different osteolytic pathologies. This retrospective observational study aimed to evaluate the long-term clinical and radiologic response of patients with ABCs of the mobile spine treated with denosumab and propose an updated treatment algorithm. Six patients with relapsed and symptomatic ABCs of the mobile spine were treated with denosumab (120 mg subcutaneously on days 1, 8, 15, 29, and every 4 weeks thereafter) between 2012 and 2023. Disease assessments were conducted using CT and MRI at 3, 6, 9, and 12 months post-treatment. Clinical data, including pain levels, symptoms, and adverse events, were documented from patients' charts. Patients underwent an initial phase of treatment with denosumab, receiving a mean of 22 administrations (range 13-42) over a median follow-up period of 41 months (range 15-98 months). Clinical improvement was observed in all patients after 4 weeks of treatment, and all patients demonstrated a radiological response after 12-24 weeks on denosumab. Three patients were progression-free after discontinuing denosumab following 13, 15, and 42 administrations, respectively. At the last follow-up, after 38, 43, and 98 months, these patients remained stable without relapse of the disease. Three patients had a relapse of disease after denosumab; two of them underwent denosumab re-challenge, while one patient received one mesenchymal stem cells (MSCs) injection. All patients showed clinical and radiological improvement and were resulted to be disease-free at the last follow-up. This study demonstrates the long-term efficacy and safety of denosumab in treating ABCs of the mobile spine, as well as the potential of re-challenge in managing recurrence. A treatment algorithm is proposed, positioning denosumab as a viable therapeutic option after other local treatments. Careful patient selection, monitoring, and further research are necessary to optimize denosumab use for ABCs.
10.3390/jcm13154522
Proximal Femoral Intraosseous Schwannoma.
Seminars in musculoskeletal radiology
Intraosseous schwannoma is a rare benign nerve sheath tumor comprising < 1% of bone tumors. Relatively common locations for this tumor include the skull and mandible, and, to a lesser degree, the spine and sacrum. Intraosseous schwannoma involving the appendicular skeleton is exceedingly rare. The clinical and imaging presentation, as in this case, is nonspecific and includes pain in the setting of a lytic bone lesion. The first step in management is bone biopsy that often produces greater than expected pain. Definitive management is surgical.
10.1055/s-0044-1791203
Analysis of the application value of SUV in quantitative SPECT/CT for diagnosing benign and malignant bone lesions.
Hellenic journal of nuclear medicine
OBJECTIVE:To analyze the application value of standardized uptake value (SUV) in quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) based on the maximum expectation reconstruction algorithm for diagnosing benign and malignant bone lesions. SUBJECTS AND METHODS:A retrospective analysis was conducted on the clinical data of 83 patients suspected of bone metastasis who underwent quantitative SPECT/CT bone scans in our hospital from September 2023 to July 2024. A total of 91 high-metabolic bone lesions were outlined for SUV measurement, while the spinal SUV of patients with normal bone metabolism were outlined as the control group (46 vertebral bodies). The maximum SUV (SUVmax), mean SUV (SUVmean), and minimum SUV (SUVmin) of benign lesions (benign group), malignant lesions (malignant group), and the control group were measured and compared. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of SUV in differentiating benign and malignant bone lesions using quantitative SPECT/CT. RESULTS:Based on the final diagnosis determined by pathology and/or imaging follow-up for 6-12 months or more, 50 malignant bone lesions and 41 benign bone lesions were identified. The levels of SUVmax, SUVmean, and SUVmin in the malignant and benign groups were higher than those in the control group, with the malignant group showing higher levels than the benign group (P<0.05). Receiver operating characteristic curve analysis showed that the areas under the curves for SUVmax, SUVmean, and SUVmin were 0.867, 0.909, and 0.896, respectively. The optimal cut-off value for SUVmax was 26.58g/mL, with a specificity of 100% and a sensitivity of 65.27%; for SUVmean, the optimal cutoff value was 12.75g/mL, with a sensitivity of 78.36% and a specificity of 93.54%; for SUVmin, the optimal cut-off value was 9.13g/mL, with a sensitivity and specificity of 81.42% and 89.87%, respectively. The diagnostic detection rate of quantitative SPECT/CT fusion imaging combined with SUVmean analysis (91.21%) was higher than that of conventional SPECT/CT fusion imaging qualitative analysis (74.73%) (P<0.05). CONCLUSION:Standardized uptake value in quantitative SPECT/CT to some extent supplements the qualitative analysis of tumor bone metastasis and benign bone lesions, offering a higher accuracy in diagnosing tumor bone metastasis and differentiating between benign and malignant lesions compared to conventional SPECT/CT bone fusion imaging.
10.1967/s002449912754
Denosumab combined with en bloc resection and arthrodesis for recurrent grade 3 giant cell tumor of bone in distal radius.
Journal of orthopaedic surgery and research
PURPOSE:This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. METHODS:A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. RESULTS:Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19-53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13-72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6-12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). CONCLUSIONS:Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. LEVEL OF EVIDENCE:level IV Therapeutic.
10.1186/s13018-024-05092-1
Safety and Efficacy of Moderate-Dose Denosumab in Fibrous Dysplasia: Observational Results from a Phase 2 Clinical Trial.
The Journal of clinical endocrinology and metabolism
CONTEXT:Fibrous dysplasia (FD) is a rare skeletal mosaic disease associated with fractures and disability. A phase 2 trial of the RANKL inhibitor denosumab (NCT03571191) reported profound reductions in lesion activity and increased lesional mineralization after 6-months of high-dose treatment. Denosumab was well-tolerated, however discontinuation was associated with severe hypercalcemia. OBJECTIVE:Investigate safety and efficacy of moderate-dose denosumab (120 mg/3 months) compared to the standard high-dose regimen. SETTING:Clinical Research Center. PATIENTS:Adults with FD. INTERVENTIONS:Eight adults received high-dose denosumab for 6 months (120mg/month with loading doses on weeks 2 and 3) followed by 8-months post-treatment observation. The protocol was amended to restart moderate-dose denosumab (120 mg/3 months) if clinically indicated. MAIN OUTCOME MEASURES:Bone turnover markers, 18F-NaF PET/CT, lesion biopsies. RESULTS:In 6 subjects who restarted moderate-dose treatment, changes in serum markers at initial and final dose were comparable (P1NP -82% and -91%, CTX -86% and -86% for moderate- and high-dose, respectively). There was no difference in 18F-NaF PET/CT lesional activity or absolute change in avid lesion volume between moderate- and high-dose regimens. Sequential tissue histological analyses in 1 subject demonstrated progressive lesional mineralization and reduced cellularity with moderate-dose treatment. Bone turnover markers on moderate-dose treatment showed sustained decline in 4 subjects, however 2 severely affected subjects developed rebound between doses, with recurrent hypercalcemia in 1 subject. CONCLUSIONS:Moderate-dose denosumab may provide clinical benefits comparable to the high-dose regimen in adults with FD, while potentially lowering associated risks. However, discrepancies in duration of efficacy are an important potential safety concern.
10.1210/clinem/dgae867
Clinical-proteomic classification and precision treatment strategy of chordoma.
Cell reports. Medicine
Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.
10.1016/j.xcrm.2024.101757