Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness.
METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness.
RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients\' LRFS and OS.
CONCLUSIONS: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

UNASSIGNED: The potential risks of denosumab on pediatric patients have raised concerns about its safety. This article aims to analyze the adverse effects of denosumab in minors, with a specific focus on hypercalcemia.
UNASSIGNED: A case study involving a child was analyzed. The OpenVigil 2.1 was utilized to extract adverse event data from the FAERS database, focusing on denosumab as the primary suspect drug in pediatric patients. The study also reviewed published cases of children developing hypercalcemia after discontinuing denosumab.
UNASSIGNED: The incidence of denosumab induced hypercalcemia in individuals under 18 years old is significantly higher than the overall incidence. The signal value for hypercalcemia was higher in the male group and was highest in the adolescent group. Hypercalcemia usually appeared approximately 4 months after denosumab discontinuation. Males had a higher peak blood calcium level. Patients aged 0-11 years had a higher average peak serum calcium compared to aged 12-17 years.
UNASSIGNED: This study highlights the risk of hypercalcemia after discontinuation of denosumab in minors, with young age and male gender identified as potential high-risk factors. These findings offer valuable safety warnings and preventative measures for the secure administration of this drug in pediatric populations.

OBJECTIVE: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients.
METHODS: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55-90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed.
RESULTS: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%-15% taking oral bisphosphonates.
CONCLUSIONS: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.
目的： 探讨地舒单抗（DENOS）与唑来膦酸（ZOL）治疗新诊断多发性骨髓瘤骨病（MBD）的疗效及安全性。 方法： 回顾性分析2021年3月1日至2023年6月30日解放军总医院第五医学中心血液病医学部收治的80例新诊断MBD患者的临床资料。18例伴重度肾损害（SRI）患者[内生肌酐清除率（CrCl）<30 ml/min]均接受DENOS治疗，62例非SRI患者分为DENOS组（30例）和ZOL组（32例）。 结果： 80例MBD患者中26例（33%）发生低钙血症，22例发生于第1次用药后。非SRI患者中DENOS组低钙血症发生率高于ZOL组[20%（6/30）对13%（4/32），P=0.028]，SRI患者低钙血症发生率为89%（16/18）。多因素分析显示，CrCl<30 ml/min与DENOS治疗后低钙血症相关（P<0.001）。抗骨吸收药物治疗1个月后，DENOS组SRI、非SRI患者血清Ⅰ型胶原交联羧基端肽β特殊序列降低率大于ZOL组（68%对59%对27%，P<0.001），DENOS组SRI、非SRI患者血清Ⅰ型原胶原氨基端前肽升高率大于ZOL组（34%对20%对11%，P<0.05）。抗骨吸收药物治疗后各组全段甲状旁腺激素升高。所有患者均未发生抗骨吸收药物相关颌骨坏死及肾脏不良事件，各组血液学总有效率、完全缓解率、严格意义的完全缓解率差异均无统计学意义（P值均>0.05），中位无进展生存及总生存时间均未达到。 结论： DENOS治疗MBD具有较强的抗骨吸收作用和低肾毒性，低钙血症是常见不良反应，多为轻中度且可控。.

UNASSIGNED: To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.
UNASSIGNED: Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.
UNASSIGNED: Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the \"primary suspected (PS)\" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.
UNASSIGNED: Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).

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Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS on osteoclast activity and chondrocyte apoptosis using tartrate-resistant acid phosphatase (TRAP) assay, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and TUNEL staining. To assess the impact of DS on the NF-κB pathway, we performed Western blot and immunofluorescence staining. Additionally, we used an OA model to explore the influence of DS on subchondral bone remodeling and cartilage degeneration in vivo. We found that DS hindered receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis by inhibiting the activity of the NF-κB pathway. Besides, DS alleviated reactive oxygen species (ROS)-induced apoptosis in chondrocytes by regulating the expression of genes related to apoptosis. Moreover, we observed an attenuation of OA-related subchondral bone remodeling and cartilage degeneration in vivo. Our findings indicate that DS could effectively suppress osteoclast activity and chondrocyte apoptosis, thereby mitigating OA-related subchondral bone remodeling and cartilage degeneration. These results provide a mechanistic basis for using DS to treat OA.

UNASSIGNED: This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis.
UNASSIGNED: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included.
UNASSIGNED: Of 448 randomized patients, 421 completed the study (MW031, n = 322; placebo, n = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (p = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups.
UNASSIGNED: This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis.
UNASSIGNED: NCT05215977 (ClinicalTrials.gov.).