北京若生智能科技有限公司
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denosumab (RTPR045 / RTPR 045 / DenosteRel)

✓ Approved

Reliance Life Sciences Private Limited · TNFSF11 · 单克隆抗体

什么是 denosumab？

denosumab 是一种单克隆抗体，由Reliance Life Sciences Private Limited研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Subcutaneous Injection。

药物档案

商品名RTPR045, RTPR 045, DenosteRel
公司Reliance Life Sciences Private Limited
药物类别单克隆抗体, 抗体
分子靶点TNFSF11
给药途径Injectable (Others), Subcutaneous Injection
状态Approved
来源： ClinicalTrials.gov, Reliance Life Sciences Private Limited

作用机制

分子靶点

denosumab 作用于 1 个分子靶点：

TNFSF11TNF superfamily member 11 (ODF, CD254)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

denosumab 针对 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Bone cancer✓ Approved
Musculoskeletal and connective tissue disordersOsteoporosis✓ Approved

相关研究文献

PubMedJournal of bone and mineral metabolism2026-10-27

Denosumab, clinical fractures, and osteonecrosis of the jaw in hemodialysis patients: a comparative study.

Toida Tatsunori T, Kurita Noriaki N, Fujita Akihito A, Tominaga Ryoji R et al.

Comparative effectiveness of denosumab versus bisphosphonates for overall fracture risk and medication-related osteonecrosis of the jaw (MRONJ) in patients on hemodialysis remains unclear. We compared fracture outcomes and MRONJ using linked medical-dental claims. We used the DeSC Healthcare Database to identify patients on hemodialysis with osteoporosis or prior fragility fractures prescribed denosumab or bisphosphonates from March 2015 to August 2022. Separate prevalent-user (ongoing users) and new-user (treatment initiators) cohorts were constructed. The primary outcome was all clinical fractures, including first and subsequent events; secondary outcomes were first clinical, hip, vertebral, and other fractures. The safety outcome was first MRONJ. IPTW-weighted Cox models estimated hazard ratios with 95% confidence intervals. Among 2379 prevalent-user and 1024 new-user records, mean age was 79 years, and 30-40% had a history of clinical fractures. In the prevalent-user cohort, denosumab was associated with a lower incidence of all clinical fractures than bisphosphonates. Point estimates for first-fracture outcomes generally favored denosumab but were imprecise. In the new-user cohort, the point estimates were generally similar in direction, but the results were not statistically significant. First MRONJ incidence was 0.31 and 0.65 per 100 person-years in the bisphosphonate and denosumab groups, respectively, without statistical significance. In the prevalent-user cohort, denosumab was associated with a lower incidence of all clinical fractures than bisphosphonates, whereas first-fracture associations and the new-user analysis were imprecise. These findings and the low incidence of MRONJ may inform shared decision-making regarding antiresorptive therapies.

PMID 42934321
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PubMedDiseases (Basel, Switzerland)2026-10-26

RANK/RANKL/OPG Axis Expression and Response to Anti-RANKL Therapy in Gnathic Giant Cell Lesions: A Systematic Review and Meta-Analysis.

Mahmood Darya Khalid DK, Hama Arivan Mahmood AM, Hashmi Ahmad Shoeb AS

Understanding the biological role of the receptor activator of nuclear factor-κB ligand (RANK), its ligand (RANKL), and the decoy receptor osteoprotegerin (OPG) is vital for clarifying the pathogenesis of gnathic giant cell-containing lesions and directing targeted clinical treatments. Following PRISMA 2020 guidelines and a registered PROSPERO protocol [CRD420261461026], we searched PubMed, Scopus, and Web of Science databases for human tissue-level or clinical denosumab studies (2003-2026). Quality was appraised using adapted NOS and JBI checklists. A fixed-effect inverse-variance meta-analysis pooled continuous RANK parameters between aggressive and non-aggressive CGCG subtypes. Eleven primary tissue-marker studies (259 specimens; two previously considered studies were excluded as unpublished, non peer-reviewed sources) and 10 non-overlapping clinical cohorts/case reports (58 patients total: 55 from 7 multi-patient cohorts + 3 single-case reports [Hameed, O'Connell, Kawamura]). Mononuclear stromal cells represent the pathogenetic driver, secreting RANKL to recruit RANK-expressing mature giant cells. Meta-analysis (k = 2 studies) showed that raw membrane RANK-positive cell percentages did not differ significantly between aggressive and non-aggressive phenotypes (pooled Hedges' g = 0.25, 95% CI -0.29-0.80, p = 0.36), while non-aggressive lesions showed a borderline, non-significant trend toward higher staining intensity-distribution (SID) scores (g = 0.55, 95% CI -0.00-1.11, p = 0.0506). Because this 95% CI crosses zero, and only two studies (k = 2) were pooled, this represents a non-significant trend rather than a statistically confirmed difference between aggressive and non-aggressive CGCG; both pooled estimates are, therefore, hypothesis-generating only. In clinical cohorts, denosumab achieved objective clinical and radiological tumor responses in all reported cases, enabling downstaging from disfiguring resection to conservative curettage. However, post-cessation recurrence was frequent, ranging from 37% in adults to 100% in pediatric cohorts, with pediatric patients at risk of rebound hypercalcemia. The RANK/RANKL/OPG axis, driven by RANKL-secreting mononuclear stromal cells, underlies osteolytic activity in gnathic giant cell lesions. Denosumab is an effective neoadjuvant bridge to jaw-preserving surgery but is not curative; a RANKL-independent, OPG-resistant SOFAT pathway has been hypothesized as one possible contributor to treatment failure, although this proposal is derived from a single external study and requires independent validation before any clinical inference is drawn. Close post-treatment metabolic and radiographic surveillance is warranted in pediatric patients. Prospective studies are needed to define optimal weaning protocols.

PMID 42929987
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PubMedMedical sciences (Basel, Switzerland)2026-10-26

Bone Mineral Density in Women with Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis.

Sultanova Zhanat Z, Issenova Saule S, Dissyukeyeva Yelena Y, Nukusheva Saule S et al.

This study aims to quantitatively evaluate bone mineral density (BMD) in women with functional hypothalamic amenorrhea (FHA), determine differences across skeletal sites, and summarise current evidence on the diagnosis and management of impaired bone health in this population. Methods: A systematic search of comparative studies evaluating BMD by dual-energy X-ray absorptiometry (DXA) in women with FHA or anorexia nervosa (AN) and healthy eumenorrhoeic controls was performed. Eleven studies met the eligibility criteria, five of which were included in the meta-analysis. The quantitative synthesis comprised 14 group comparisons, with lumbar spine and hip BMD analysed separately. Effect sizes were pooled using Hedges' g with 95% confidence intervals (CI) under a random-effects model. Sensitivity analyses using REML estimation with Hartung-Knapp adjustment and leave-one-out analyses were performed to assess the robustness of the pooled estimates. Results: The narrative synthesis of 11 studies generally showed lower BMD in women with FHA or AN compared with healthy controls. In the meta-analysis, among women with FHA, hip BMD was significantly lower than in healthy controls (Hedges' g = -0.60; 95% CI -1.13 to -0.06; p = 0.030; I2 = 63%), while a moderate reduction was observed at the lumbar spine (Hedges' g = -0.68; 95% CI -1.48 to 0.13; p = 0.101; I2 = 83%). In women with AN, substantial reductions were observed at both the lumbar spine (Hedges' g = -1.66; 95% CI -2.28 to -1.04; p < 0.001; I2 = 71%) and the hip (Hedges' g = -1.37; 95% CI -2.33 to -0.42; p = 0.005; I2 = 89%). The lumbar spine reduction in AN remained statistically significant across sensitivity and leave-one-out analyses and was the most robust finding, whereas the statistical significance of hip BMD estimates in both FHA and AN and of lumbar spine BMD in FHA was sensitive to the analytical approach or exclusion of individual studies. The systematic review demonstrated that DXA with interpretation based on Z-scores remains the preferred method for skeletal assessment in premenopausal women with FHA. Bone health assessment is recommended after ≥6 months of amenorrhea or earlier in women with severe energy deficiency or a history of fractures. Restoration of energy availability, weight gain, and recovery of menstrual function remain the cornerstone of treatment. When amenorrhea persists and low BMD is confirmed, physiological transdermal 17β-estradiol combined with cyclic progesterone is the preferred hormonal therapy, whereas combined oral contraceptives, bisphosphonates, and denosumab are not recommended for routine management. Conclusions: Functional hypothalamic amenorrhea is associated with reduced BMD, with substantially greater skeletal deficits observed in the AN subgroup. These findings support early assessment of bone health and timely correction of low energy availability in women with FHA. The considerable between-study heterogeneity and sensitivity of some pooled estimates highlight the need for larger prospective studies using standardized diagnostic criteria and uniform skeletal outcome measures.

PMID 42930534
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PubMedCritical reviews in oncology/hematology2026-10-25

Bone Health in Oncology: Defining Biosimilar Denosumab Use Through Multidisciplinary Collaboration.

Aapro Matti M, Coleman Robert R, Dixit Niharika N, Epstein Joel B JB et al.

Bone metastases represent a major source of morbidity in advanced solid tumors, leading to skeletal-related events (SREs), pain, and impaired quality of life. Although guidelines recommend the use of bone-modifying agents (BMAs) to prevent SREs, real-world data consistently show delayed initiation, inconsistent dosing, and poor treatment persistence for these agents. This ongoing undertreatment contributes to preventable skeletal complications, greater healthcare utilization, and diminished patient outcomes. Denosumab and bisphosphonates remain the cornerstone of bone-targeted therapy. Recent evidence indicates that sustained BMA use is strongly associated with preserved functional status, reduced bone pain, and potentially improved survival. However, access and affordability continue to limit optimal use in many settings. The introduction of denosumab biosimilars offers an important opportunity to address these barriers. Phase III trials across multiple denosumab biosimilars developed by Sandoz, Samsung Bioepis, Celltrion, and Fresenius Kabi have shown equivalent efficacy, safety, and immunogenicity to the reference denosumab, with comparable lumbar spine bone mineral density gains and low rates of adverse events. Budget-impact modeling projects substantial cost savings and expanded patient access, reinforcing their role in reducing financial toxicity and promoting more equitable bone health care. Optimal management of bone metastases requires coordinated, multidisciplinary care involving oncologists, dentists, nurses, pharmacists, radiologists, rehabilitation specialists, supportive and palliative care teams. Such collaboration ensures timely BMA initiation, preventive dental evaluation, adherence monitoring, and continuity of therapy across systemic treatment lines. Integrating biosimilars within structured, patient-centered care pathways offers a sustainable strategy to close existing treatment gaps and improve outcomes for patients with bone metastases.

PMID 42926077
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PubMedFrontiers in medicine2026-10-25

An osteogenic microenvironment improves response during denosumab treatment in giant cell tumors of bone in the spine.

Birch Robyn R, Eltit Felipe F, Ng Tony T, Rhines Laurence D LD et al.

Giant cell tumors of bone are benign but locally aggressive tumors. Typically diagnosed in individuals between the ages of 20 and 40 years, these tumors cause significant amounts of pain, and morbidity. Giant cell tumors of bone can be treated with an increased dosing regimen of denosumab, a monoclonal antibody that targets receptor activator of nuclear kappa-B ligand, which has shown promise in reducing pain and tumor size, while contributing to improved ossification of the tumor. However, the ossification response observed varies, with some patients responding rapidly with total tumor ossification, while others respond slowly, if at all. Due to gaps in our current understanding of what improves ossification in patients, we aimed to identify patient specific biomarkers that contributed to increased ossification in our patient cohort. Pre-treatment biopsy samples from 19 patients collected from 3 North American centres were grouped based on their response to denosumab, determined from their change in Boriani ossification grade after treatment. The 19 patients pre-treatment tissue was used in gene expression analysis using RNA extraction and nanoString analysis. A subset of tissue from 6 patients and 3 healthy controls were included in protein expression analysis, where differential expression and gene set enrichment analysis was conducted to identify upregulated proteins and pathways contributing to the different treatment responses. A distinct microenvironment was identified through both genetic and proteomic expression. Good responders demonstrated upregulation of TNFRSF11B and CX3CL1, genes that are related to bone remodeling, and a downregulation of CX3CR1. Additionally, tissue remodeling and cell proliferation markers were upregulated, while immune related markers were downregulated in our good responders (increased ossification of tumor). Genetic analysis was complemented by protein analysis which in our good responders demonstrated upregulation of bone pathways associated with bone development, bone mineralization, ossification, and osteoblast differentiation, and downregulation in bone remodeling, bone resorption, and osteoclast differentiation. Further analysis identified upregulation of LTF, FBLN5, LOX, CHAD, and OGN, and downregulation of CEBPB, CTSK, and TFRC. Giant cell tumors of bone show varied mineralization responses to denosumab, with the biological factors associated with this variability remaining poorly understood. We used gene and protein expression analysis of pre-treatment biopsy tissue to compare good and poor mineralization responses. The good responders demonstrate a pre-treatment tumor microenvironment that favors bone formation and reduced resorption, suggesting that biomarker analysis of biopsied samples may help to understand a patient's response to denosumab and guide personalized treatment strategies.

PMID 42922809
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PubMedJournal of dental sciences2026-10-25

Biphasic remodeling and trabecular-cortical uncoupling in the jawbone during antiresorptive therapy and medication-related osteonecrosis: A quantitative imaging analysis.

Wei Ling-Ying LY, Lee Jun-Ching JC, Chiu Ching-Ming CM, Kok Sang-Heng SH et al.

Although antiresorptive therapy (ART) is crucial for managing oncology-related skeletal complications, it carries a risk of medication-related osteonecrosis of the jaw (MRONJ). Because conventional radiography relies on subjective interpretation, detecting early necrotic transition remains challenging. This study aimed to establish objective, quantitative imaging criteria for jawbone remodeling and MRONJ onset by evaluating 2D fractal dimension (FD) and 3D CBCT cortical thickness under zoledronic acid or denosumab therapy. Panoramic radiographs and CBCT scans of cancer patients receiving zoledronic acid (ZA, n = 155) or denosumab (Dmab, n = 168), and healthy controls (n = 95) were analyzed. Longitudinal FD and contralateral and lesion-site cortical thicknesses were quantified to differentiate systemic remodeling from localized necrosis. Systemic ART induced widespread jawbone osteosclerosis, characterized by significant longitudinal FD increases (ZA: P < 0.05; Dmab: P < 0.001) and contralateral cortical thickening (P < 0.05). Conversely, MRONJ onset triggered a distinct trabecular-cortical uncoupling: a paradoxical reduction in FD (osteolysis) at the necrotic site (P < 0.05) concurrent with reactive periosteal cortical thickening, most pronounced on the lingual aspect (P < 0.001). ZA induced diffuse sclerosis, whereas Dmab-induced changes were localized to the anterior mandible. Jawbone trabecular and cortical compartments exhibit distinct remodeling patterns during ART and osteonecrosis. Combining quantitative assessments of these compartments provides an objective, non-invasive method for monitoring skeletal burden and detecting early necrotic transitions before clinical bone exposure occurs.

PMID 42924146
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