Prolia (denosumab) / Amgen, BeOne Medicines, Daiichi Sankyo - LARVOL DELTA

Combined treatment with radium-223 (RAD) and enzalutamide (ENZ) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Insights from the global REASSURE study (ESMO 2025) - P, P3 | "Incidence of fractures was slightly higher in ALL pts (10%) with fewer pts receiving concomitant BPAs (denosumab 28% and zoledronic acid 13%)...Table: 2401P ENZ/RAD (N=45) ALL Pts (N=1,472) Median time since initial diagnosis of bone metastases to study entry, months 14 23 Median time since castration resistant cancer to study entry, months 7 13 Extent of disease, % Bone only metastases 80 81 Bone metastases + lymph node only 9 13 Disease burden, % 20 metastases but not Superscan 18 20 Superscan 4 6 Laboratory values, median ALP (U/L) 131 133 PSA (ng/mL) 33 59 Prior abiraterone, % 40 48 Prior docetaxel, % 16 39 Prior Sipuleucel-T, % 18 9 Conclusions In this subgroup of pts treated with combined ENZ/RAD in a real-world setting, there was no new safety signal...Pts received ENZ/RAD earlier in the disease course based on time from mCRPC, time from initial diagnosis of bone metastases and prior docetaxel. Fracture incidence was low in ENZ/RAD, and the majority of pts..."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Treatment Sequencing of CDK4/6 Inhibitors in Bone-Only Hormone Receptor-Positive Metastatic Breast Cancer: Multi-Center Real-World Data Revealing a Numerical Trend Favoring Later-Line Use. (PubMed, Cancers (Basel)) - "In HR+/HER2- MBC patients with bone-only disease, first-line CDK4/6 inhibitor therapy demonstrates a trend toward superior PFS. After correcting for key observational biases, the later line of therapy does not independently alter OS. These findings reinforce that first-line CDK4/6 inhibitor plus endocrine therapy remains the definitive standard of care, and later-line initiation should be reserved solely for select clinical scenarios where first-line use was not feasible."

Journal • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Osteonecrosis of the jaw (ONJ) in patients with metastatic breast cancer treated with denosumab in a randomized phase III trial comparing 4 vs. 12 weekly administration (REDUSE, SAKK 96/12) (SABCS 2024) - P3 | "The observed ONJ rate of 8.1% in the standard arm is in line with the literature for patients who received DN q4w for more than two years (6.0% to 9.8%). Administration of DN q12w reduces the risk of ONJ and/or tooth infections substantially. This risk reduction is clinically relevant with an absolute difference of 6.2% for ONJ and/or tooth infection after a median follow-up of 3.4 years."

Clinical • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor

Real world outcomes comparing denosumab and zoledronic acid in patients with metastatic renal cell cancer with bone metastases: A propensity score matched analysis from global federated health research network (ESMO 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Fibrosarcoma of bone masquerading as fibrous dysplasia: diagnostic pitfall and molecular correlates of aggressive behavior. (PubMed, J Pathol Transl Med) - "The patient remains alive with disease at 27 months after presentation. This case highlights a diagnostic pitfall in which low-grade fibrosarcoma with denosumab-associated ossification may mimic fibrous dysplasia and underscores the prognostic value of molecular profiling beyond histologic grading."

Journal • Fibrosarcoma • Musculoskeletal Diseases • Oncology • Orthopedics • Osteosarcoma • Sarcoma • Solid Tumor • GNAS • KIT • PDGFRA

Long-term outcomes of adjuvant denosumab in breast cancer: Fracture reduction and survival results from 3,425 patients in the randomised, double-blind, placebo-controlled ABCSG-18 trial. (ASCO 2022) - P3 | "Adjuvant Dmab 60mg every 6 months during AI therapy is safe, and markedly reduces treatment-induced clinical fractures even in the long-term. DFS, BMFS, and OS are improved in this descriptive final long-term analysis of ABCSG-18. Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer."

Clinical • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Diseases • Oncology • Solid Tumor

Pharmacological therapies for the prevention of fractures in men. (PubMed, Cochrane Database Syst Rev) - "We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men."

Clinical • Journal • Review • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Fracture Risk Associated With Long-Term Discontinuation of Postmenopausal Osteoporosis Treatment: A French Population-Based Study Using National Claims Data (Système National des Données de Santé). (PubMed, ACR Open Rheumatol) - "We observed high rates of LTD of osteoporosis treatments among postmenopausal women in France, with LTD of oral bisphosphonates increasing fracture risk by 12% and LTD of denosumab almost doubling fracture risk. These data underscore the need for careful LTD decision-making, especially for denosumab."

Journal • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Is C-Terminal Telopeptide Associated With Medication-Related Osteonecrosis of the Jaw Risk Following Extraction in Osteoporosis Patients Treated With Denosumab? (PubMed, J Oral Maxillofac Surg) - "Lower CTX levels and greater number of extractions were associated with increased risk for developing MRONJ among patients with osteoporosis treated with denosumab who require dental extractions."

Journal • Metabolic Disorders • Orthopedics • Osteoporosis • Rheumatology

Medication-related osteonecrosis of the external auditory canal and treatment with teriparatide. (PubMed, JCEM Case Rep) - "A 67-year-old woman developed left-sided MROEAC after 15 years of alendronate followed by a short course of denosumab. Teriparatide was well tolerated and was associated with increased bone turnover markers, but radiologic resolution was incomplete. Surgical management may still be necessary."

Journal • Otorhinolaryngology

Patterns of Osteoporosis Treatment Initiation Following Low-Trauma Fracture: A Population-Based Retrospective Cohort Study in New South Wales, Australia, Using Linked Administrative Health Data. (PubMed, Med J Aust) - "More than three-quarters of individuals remain untreated after fracture, highlighting persistent and substantial gaps in secondary fracture prevention. Treatment initiation is strongly associated with fracture site and multimorbidity burden, and initiation rates are lower in males. Increasing reliance on denosumab underscores the need for careful long-term treatment planning and strategies."

Journal • Retrospective data • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

A pilot study evaluating denosumab in symptomatic knee osteoarthritis patients with elevated subchondral bone metabolic activity detected by PET/MRI (ChiCTR) - P=N/A | N=20 | Not yet recruiting | Sponsor: Shanghai Sixth People's Hospital; Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

New trial • Immunology • Osteoarthritis • Rheumatology

Real world outcomes comparing denosumab and zoledronic acid in patients with metastatic thyroid cancer with bone metastases: A propensity score matched analysis from global federated health research network (ESMO 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Revealing the Potential Mechanism for Extracellular Matrix Remodeling via Mechanical Stimulation in Myeloma Bone Disease (IMS 2026) - "However, current treatment strategies using bone-modifying agents like bisphosphonates or denosumab only suppress bone resorption without stimulating sufficient bone repair through bone remodeling... We demonstrate that bone marrow-resident MM cells induce ECM alterations in the tumor microenvironment, and that biophysical stimuli could counteract these changes. Moreover, the analysis of the cancer genome atlas indicates that the tumor cell-derived ECM signature can strongly distinguish among myeloma cell types, suggesting that changes in ECM composition of the tumor microenvironment might be relevant for the prediction of disease stage and patient prognosis."

Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Orthopedics • CCL2

Giant Cell Tumor of the Distal Humerus: A Rare Location With a Good Response to Denosumab. (PubMed, Cureus) - "Its use increases the risk of calcium-phosphorus abnormalities and growth disorders. Our case demonstrated that a well-defined treatment regimen combined with calcium-phosphorus supplementation could control the aggressiveness of GCTs."

Journal • Endocrine Disorders • Giant Cell Tumor of Bone • Oncology • Osteosarcoma • Pain • Pediatrics • Solid Tumor

Refractory Rebound Hypercalcemia Following Abrupt Denosumab Withdrawal in an Adult With Myeloma-Related Bone Disease: A Clinically Challenging Metabolic Surge (SOHO 2026) - "Her disease was in remission after induction therapy followed by autologous stem cell transplant; she was currently on maintenance lenalidomide...Multiple hospitalizations ensued, and her hypercalcemia proved refractory to hydration, calcitonin, and repeated zoledronic acid infusions... Rebound hypercalcemia is a rare side effect of denosumab in adults and stems from rapid restoration of osteoclastogenesis and accelerated bone resorption when RANKL inhibition abruptly ceases. Individuals with prolonged antiresorptive exposure or high-turnover bone disease are particularly vulnerable. Pooled safety data from the FDA reported that 0.7% of patients experience rebound hypercalcemia following discontinuation of denosumab across all tumor types."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Urothelial carcinoma of the bladder with prostatic stromal invasion and early postoperative bone metastases: a case report. (PubMed, Front Urol) - "He subsequently received denosumab combined with conformal intensity-modulated radiotherapy to vertebral metastatic lesions...For patients with bladder neck or prostatic masses, especially those with normal PSA but imaging evidence of bladder-prostate junction involvement, an immunohistochemical panel including GATA3, CK7, CK20, p63, Uroplakin III, PSA, and NKX3.1 should be used early for differential diagnosis. Prostatic stromal invasion combined with lymphovascular invasion, perineural invasion, and a positive surgical margin may indicate highly aggressive disease and an increased risk of early distant metastasis, requiring intensified postoperative risk assessment, systemic treatment decision-making, and close follow-up."

IO biomarker • Journal • Back Pain • Benign Prostatic Hyperplasia • Bladder Cancer • Lumbar Back Pain • Musculoskeletal Pain • Oncology • Pain • Prostate Cancer • Solid Tumor • Urothelial Cancer • GATA3 • HER-2 • KRT20 • NKX3-1 • PD-L1 • TP63 • UPK3

Osteonecrosis of the jaw (ONJ) in patients with metastatic castration resistant prostate cancer (mCRPC) treated with denosumab in a randomized phase III trial comparing 4 vs. 12 weekly administration (REDUSE, SAKK 96/12). (ASCO-GU 2025) - P3 | "Administration of DN q12w reduces the risk of ONJ. This risk reduction of ONJ or TI is clinically relevant with an overall absolute difference of 1.6% for all grades and 1.9% for ≥3 after a median follow-up of 2.4 years. Efficacy data for time to first SSE (the primary endpoint of this trial) is not yet mature and will be reported later."

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Potent bisphosphonate therapy for preventing fractures after denosumab discontinuation in osteoporosis: A GRADE-assessed systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "Potent BP therapy was related to decreased vertebral fracture risk after denosumab termination, particularly when compared with no subsequent therapy. Evidence versus SERM comparators was limited and inconclusive. The results are in agreement with the present clinical guideline recommendations for sequential BP use after the discontinuation of denosumab, but further high-quality randomized trials are required to prove this."

Clinical • Journal • Retrospective data • Review • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Efficacy and safety of zoledronic acid versus denosumab in the treatment of primary osteoporosis: a single-center retrospective cohort study. (PubMed, Front Endocrinol (Lausanne)) - "Denosumab exhibits superior long-term efficacy over zoledronic acid in improving bone mineral density and suppressing bone turnover. Both agents demonstrate excellent safety profiles and represent effective therapeutic options for the management of osteoporosis."

Biomarker • Clinical • Journal • Retrospective data • Osteoporosis • Rheumatology • COL1A2

Q6W Versus Q4W Denosumab in Lung Cancer With Bone Metastases: A Randomized Non-Inferiority Trial (IASLC-WCLC 2026) - "Results were consistent between ITT and PP analyses. Conclusions : The Q6W regimen of denosumab demonstrated non-inferiority to Q4W in bone PFS and may serve as a clinically acceptable alternative with improved convenience."

Clinical • Head-to-Head • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Direct medical costs of de-escalated denosumab in patients with bone metastases: within-trial analysis of the randomized phase III non-inferiority trial SAKK 96/12 REDUSE (ESMO 2026) - No abstract available

Clinical • Head-to-Head • HEOR • P3 data • Oncology • Solid Tumor

Real world outcomes comparing denosumab and zoledronic acid in patients with metastatic prostate cancer with bone metastasis: A propensity score matched analysis from global federated health research network (ESMO 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Quality of life in patients with bone metastases receiving reduced denosumab: A randomized phase III non-inferiority trial SAKK 96/12 REDUSE (ESMO 2026) - No abstract available

Clinical • Head-to-Head • HEOR • P3 data • Oncology • Solid Tumor

Comparative Effectiveness of Sequential Romosozumab-Denosumab vs. Denosumab Alone on Fracture Risk: A Target Trial Emulation Study (ACR Convergence 2026) - No abstract available

HEOR • Musculoskeletal Diseases • Orthopedics