zoledronic acid / Generic mfg. - LARVOL DELTA

Synergistic enhancement of γδ T cell cytotoxicity against tumor spheroids through B7H3 CAR and zoledronate sensitization (ASH 2025) - "From this we can conclude that armoring γδ T cells imparts antigen specificity, but this must be analyzed in the context of the strong cytotoxic activity mediated by the innate immune receptors present on activated γδ T cells. These findings support further investigation into the combined use of pre infusion of zoledronate and CAR γδ T cells as a strategy to potentiate cytotoxic responses against human solid tumors."

IO biomarker • Brain Cancer • Breast Cancer • Glioblastoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Ovarian Cancer • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • CD276 • IL15 • IL2

Early intervention in smoldering multiple myeloma: A systematic review of comparative prospective trials (ASH 2025) - "Two studies were phase I/II trials, one comparing the use of dose-escalated multipeptide PVX-410 vaccine +/- lenalidomide (R) in SMM patients, and the other comparing dose-escalated anakinra +/-Lenalidomide/dexamethasone (Rd)...Two studies were phase II RCTs; one compared Rd +/- Carfilzomib (K) in 58 high-risk SMM patients, with statistically significantly higher 3-year PFS in KRd of 94% versus Rd of 40%; p<0.001, across a median follow-up period of 34 months...The second phase II RCT included 20 intermediate- and high-risk SMM patients treated with Iberdomide (I) +/- d, with ORR of 84.6% versus 80% in the Id versus I group...One phase III RCT compared zoledronic acid +/- thalidomide in a total of 68 SMM patients, with a median TTP of 2.4 versus 1.2 years, 1-year PFS of 85% versus 55%, and 1-year ORR of 37% versus no confirmed response during the median follow-up of 5.9 years... Preliminary evidence from comparative trials suggests that early treatment of..."

Clinical • Review • Hematological Malignancies • Multiple Myeloma • Smoldering Multiple Myeloma

Comparative efficacy of therapeutic interventions for thalassemia-induced osteoporosis: A network meta-analysis (ASH 2025) - "Compared with control, significant improvement in BMD at Total Hip or Femoral Neck (Z-score) was observed in Zoledronic Acid [MD = 0.51; 95% CI: 0.27 to 0.75], Alendronate [MD = 0.37; 95% CI: 0.20 to 0.54], Pamidronate [MD = 0.27; 95% CI: 0.01 to 0.54], and Zinc [MD = 0.26; 95% CI: 0.09 to 0.43]. It emphasizes the critical role of bisphosphonates, nutritional supplementation, and novel agents in enhancing bone health and overall quality of life for this patient population. These findings provide essential guidance for clinicians in optimizing osteoporosis management for individuals with thalassemia."

Retrospective data • Beta-Thalassemia • Genetic Disorders • Osteoporosis • Rheumatology

Fingolimod in combination with bortezomib demonstrates synergistic tumor inhibition and bone anabolic effects in myeloma bone disease (ASH 2025) - "In mouse bone explants, fingolimod (10-100 nM) demonstrated dual effects:increasing osteoblast markers (alkaline phosphatase, osteocalcin mRNA) and osteocyte differentiation(DMP1 mRNA) while simultaneously suppressing osteoclast markers (ACP5/TRAcP, cathepsin K mRNA),contrasting with zoledronic acid's exclusive osteoclast inhibition. Fingolimod, at clinically achievable doses, synergizes with bortezomib through dualmechanisms: 1) direct disruption of sphingolipid-mediated survival pathways in tumor cells 2) remodelingthe BME by coupled osteoclast inhibition/osteoblast activation, including systemic osteo-protection,suggesting neutralization of circulating osteolytic factors. Future work includes validation in PDX models,sphingolipid-risk biomarker development, and Phase Ib trials in relapsed/refractory MM with bonedisease. Fingolimod's established safety profile as an oral multiple sclerosis therapy enables rapid clinicaltranslation."

Combination therapy • IO biomarker • CNS Disorders • Hematological Malignancies • Multiple Myeloma • Multiple Sclerosis • Oncology • Orthopedics • Plasmacytoma • BCL2 • CTSK • IL6 • MCL1 • SPHK2 • TNFA • TRAP

Final analysis of the evaluation of safety and efficacy of denosumab in patients with multiple myeloma and severe renal impairment: An IMWG bone subcommittee study (ASH 2025) - "Renal impairment (RI), a cardinal feature of MM, further complicates treatment strategies.Denosumab, a bone-directed agent, has demonstrated non-inferiority to zoledronic acid but its efficacyand safety in patients with severe RI remains underexplored. Denosumab 60 mg, monthly,seems to be sufficient to prevent both SREs and hypocalcemia. However, further prospective researchwith larger cohort and longer follow-up period will confirm these results and refine treatment guidelines."

Clinical • Chronic Kidney Disease • Endocrine Disorders • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Musculoskeletal Diseases • Orthopedics • Renal Disease

The allogeneic fully human anti-CD38-CAR-γδ T cells enable off-the-shelf CAR-T cell therapy for myeloma (ASH 2025) - "Introduction The prognosis for myeloma patients has been improved by proteasome inhibitors (PIs),immunomodulatory drugs (IMiDs), and antibodies, particularly anti-CD38 antibodies such asdaratumumab and isatuximab...Thus, weattempted to develop fully human anti-CD38-CAR γδ T cells for repetitive off-the-shelf use in myelomapatients.Methodsγδ T cells were cultured using zoledronic acid and IL-2 and expanded from PBMCs of healthy donors...TheseCAR-γδT cells have fully human scFv and MHC-unrestricted cytotoxicity, so they can be used multipletimes, which is economically advantageous. Allogeneic fully human anti-CD38-CAR γδ T cells may shednew light on the treatment of myeloma patients as an off-the-shelf therapeutic agent, potentially leadingto an increase in cutting-edge treatment options."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • IL2

Novel γδ T cell engager platform for cancer immunotherapy promoted T cell expansion with a persistence-indicating phenotype (ASH 2025) - "Here, we present initial findings from a novel activating γδ T cellengager platform (γδ-TCE) targeting CD19+ B cell hematologic malignancies (INB-619). In vitro cytolytic function and EC50 were determined by addition of incremental concentrationsof INB-619 (0 to 10 nM) to co-cultures of equal numbers of the NALM-6 B-ALL cell line and γδ T cellsderived from peripheral blood mononuclear cells (PBMCs) in a 1:1 effector to target (E:T) ratio...Controlsincluded PBMC alone, PBMC + 10%NALM-6, and PBMC + 10% NALM-6 + Zoledronate as a control for γδ Tcell function... By combining meaningful effector cell expansion, strong anti-tumor activity, and a low CRS-associated cytokine profile, this innovative γδ TCE platform presents a promising new approach to cancerimmunotherapy. Additionally, its modular and flexible design suggests potential uses across a wide rangeof cancer targets by leveraging the innate recognition capabilities of γδ T cells with targeted engagementof specific..."

Hematological Malignancies • Leukemia • Oncology • CD27 • IFNG • TNFA

Optimizing skeletal health: An analysis of bone-modifying agent prescription patterns and incidence of skeletal-related events in multiple myeloma (ASH 2025) - "Afterthe diagnosis of MM, 185 patients (85.6%) were prescribed BMA (75.1% zoledronate, 11.4% denosumaband 12.4% Pamidronate). Among patientswho received BMA, 17.8% developed SREs predominantly between two to five years after the first dose,which is comparable to previous studies. Future studies may look into initiatives to improve guidelineadherence."

Hematological Malignancies • Multiple Myeloma • Musculoskeletal Diseases

Severe cutaneous adverse reactions to anti-osteoporosis drugs: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database and a review of published cases. (PubMed, Front Pharmacol) - "Denosumab (24%), alendronate (23.25%), and zoledronic acid (17.13%) were most frequently reported. Anti-osteoporosis drugs, notably bisphosphonates and strontium ranelate, are rarely linked to SCARs but may cause serious consequences. Increased clinical awareness, pre-treatment risk evaluation, and vigilant monitoring are essential for at-risk patients."

Adverse events • Journal • Real-world evidence • Dermatology • Osteoporosis • Rheumatology • Steven-Johnson Syndrome • Vasculitis

The Mitigating Effect and Mechanism of Polydeoxyribonucleotide Against Zoledronic Acid-Induced Growth Suppression of Human Gingival Fibroblasts. (PubMed, Int J Mol Sci) - "Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. The antioxidant N-acetylcysteine (NAC) similarly reduced ZA-induced ROS and p-TBK1 levels and improved cell growth, although it had limited effects on p-PKB at 8 h. Importantly, delayed PDRN treatment following ZA exposure reversed ZA-induced cell growth inhibition and TBK1 activation in a dose- and time-dependent manner. In summary, these findings demonstrate that ZA suppresses HGF-1 cell growth through ROS production, TBK1 activation, and inhibition of PKB and STAT-3, whereas PDRN counteracts these effects primarily by suppressing TBK1 activation and oxidative stress."

Journal • Oncology • Osteoporosis • Rheumatology • Solid Tumor • STAT3

Effect of zoledronic acid on recurrent vertebral fractures after percutaneous vertebroplasty. (PubMed, J Orthop) - "Post-PVP ZA administration improved BMD, delayed secondary fractures, and reduced bone turnover in OVCF patients, thereby promoting better clinical outcomes. An appropriate bone cement volume also contributed to prolonged fracture-free intervals."

Journal • Musculoskeletal Diseases • Orthopedics • Pain

How to optimize the use of anti-osteoporotic medication in clinical practice? (PubMed, Expert Opin Pharmacother) - "New data are available to guide the choice of start and sequence of anti-resorptives and osteo-anabolics according to the level of fracture risk in postmenopausal women, in patients treated with glucocorticoids, after a hip fracture and in patients treated with a treat to target strategy. Integrating FRAX, the level of aBMD, a detailed fracture history including imaging of the spine, and additional risk factors contributes to decide on treatment with antiresorptive-treatment (in high-risk subjects) and osteoanabolic-treatment (in very high-risk subjects) and their sequence to achieve a target with a low fracture risk which needs lifelong follow up for further diagnostic and treatment decisions."

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

Treatment trends after hip fracture of veterans with osteoporosis. (PubMed, J Clin Densitom) - "Hip fractures have a large impact on morbidity and mortality in the older population. Our study shows opportunity for increased utilization of parenteral therapies in patients who fractured on a background of oral bisphosphonate therapy. Delays may be the result of several issues including cost, recognition of fracture risk change, lack of communication, and comfort with therapies. The low percentage of parenteral medication use indicates some opportunity for more potent treatment. Future research directions could analyze civilian databases to get a more generalizable data set."

Journal • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Characterization of Stimulated γδ T Cells: Phenotypic Analysis and Implications for Allogeneic Cellular Immunotherapy. (PubMed, Cells) - "By investigating correlations between the phenotype of unstimulated γδ T cells and cellular cytotoxicity, as well as the degranulation ability of stimulated γδ T cells, we could draw conclusions about optimal donors for further allogeneic cellular therapies. Finally, we demonstrated that the phenotype varies over the time of culture and is clearly modifiable by changing the stimulation protocol."

Journal • Oncology

Clinical and functional outcomes of neo-adjuvant zoledronic acid therapy and valgus osteotomy in proximal femoral fibrous dysplasia. (PubMed, J Clin Orthop Trauma) - "Valgus osteotomy, stabilized with intra- or extramedullary fixation remains a valuable technique for managing FD-associated deformities. Further prospective studies are warranted to refine treatment protocols and validate long-term outcomes."

Journal • Musculoskeletal Diseases • Orthopedics • Pain

Refractory hypercalcemic crisis: A case of primary hyperparathyroidism with Gitelman syndrome. (PubMed, J Int Med Res) - "The patient experienced recurrent hypercalcemic crises that required treatment with zoledronic acid and denosumab after conventional interventions failed. This case emphasizes that hypocalciuria in the setting of persistent hypercalcemia-especially when severe hypomagnesemia is present-should raise suspicion for underlying Gitelman syndrome. Early identification of this coexistence is essential, as optimal management requires surgical treatment of primary hyperparathyroidism followed by targeted correction of electrolyte abnormalities associated with Gitelman syndrome, ultimately improving clinical outcomes."

Journal • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease

Efficacy of zoledronic acid in peri-menopausal women with osteopenia. (PubMed, J Bone Miner Metab) - "In peri-menopausal women with osteopenia with a T-score of - 1.75 to - 2.5, a single infusion of zoledronic acid increased lumbar spine and femoral neck BMD and suppressed the high bone turnover. Zoledronic acid thus could be used for preserving bone density and preventing the risk of osteoporosis and fragility fractures in the future."

Journal • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study. (PubMed, Orphanet J Rare Dis) - "This prospective cohort study provides evidence that implementing an effective and rational treatment protocol during tooth extractions significantly benefits high-risk MRONJ patients. Adherence to such protocols minimizes the risk of postoperative infection, fosters improved healing of extraction sites, and maximizes the prevention of MRONJ."

Journal • Dental Disorders • Infectious Disease • Oncology • Osteoporosis • Periodontitis • Rheumatology

Spinal Cord Infarction Following Zoledronic Acid Administration in a Patient With Metastatic Prostate Cancer. (PubMed, Cureus) - "Past medical history included metastatic prostate cancer, osteoporosis, deep vein thrombosis on apixaban, and a complex oncologic and spinal history. This case highlights an uncommon but devastating neurologic complication in the context of complex oncologic care and prompts the consideration of potential vascular risks of bisphosphonates in patients with prior spinal metastases, radiation, and surgery. It also emphasizes the diagnostic complexity and the potential for rehabilitation in spinal cord infarction with multifactorial oncologic and vascular compromise."

Journal • Back Pain • Cardiovascular • CNS Disorders • Genito-urinary Cancer • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Nephrology • Oncology • Pain • Prostate Cancer • Rheumatology • Solid Tumor • Thrombosis • Urinary Incontinence • Urology

Rescuing Mitochondrial Dysfunction in Macrophages Prevents Osteonecrosis of the Jaw in Anti-Resorptive Therapy. (PubMed, Adv Sci (Weinh)) - "This study demonstrates that zoledronic acid (ZA) disrupts mitochondrial bioenergetic function in macrophages, leading to elevated mitochondrial membrane potential, excessive mitochondrial reactive oxygen species (mtROS), and increased HIF-1α expression, which together promote a pro-inflammatory transition in macrophages...To restore mitochondrial degradation and biofunction, ZA-loaded nanoparticles incorporating the mTOR inhibitor rapamycin (ZDPR) are developed. ZDPR effectively prevents BRONJ and exerts therapeutic benefits in osteoporosis and osteolysis. These findings highlight bone-targeted mitochondria rescue as a promising strategy to enhance antiresorptive therapy."

Journal • Inflammation • Metabolic Disorders • Osteoporosis • Rheumatology • ATG5 • HIF1A • MYD88 • TLR4

Aromatase inhibitors and medication-related osteonecrosis of the jaw: friends, foes, or bystanders? (PubMed, Crit Rev Oncol Hematol) - "Letrozole was the most frequently prescribed AI, followed by anastrozole and exemestane. MRONJ was reported in 43 studies, with 1,147 cases among 45,121 AI users (2.5% of AI users in the included samples), the majority of whom were concomitantly treated with zoledronic acid and/or denosumab...Data demonstrate the difficulty of disentangling the effects of AI from those of antiresorptive therapy in MRONJ pathogenesis. Future research should consider AI as potential confounders in analytical studies to clarify their independent contribution, if any, to observed MRONJ occurrences."

Journal • Review • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Efficacy of Zoledronic Acid on Bone Mineral Density in Boys With Duchenne Muscular Dystrophy: A Prospective Observational Study. (PubMed, Pediatr Neurol) - "Intravenous ZA significantly improved BMD and reduced bone turnover in boys with DMD without major adverse effects."

Journal • Observational data • Back Pain • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain

Bone modifying agents and multikinase inhibitors as treatments for chordoma: A TriNetX-based retrospective cohort study. (PubMed, Clin Neurol Neurosurg) - "This study highlights potential differences in survival and skeletal-related outcomes among chordoma patients treated with BMAs, specifically denosumab and MKIs. These preliminary findings underscore the need for prospective studies to better define optimal systemic therapies for this rare malignancy."

Journal • Retrospective data • Chordoma • CNS Disorders • Embryonal Tumor • Musculoskeletal Diseases • Oncology • Orthopedics • Solid Tumor

Combined innate immune cell therapy, tumor-specific antibody, and radiation prompt antitumor response in pancreatic cancer models. (PubMed, Sci Adv) - "We combine an innate cell-enriched product activated by interleukin-2 (IL-2) and zoledronic acid (ZA) (ICPIL2ZA) with low-dose radiotherapy (RT) and monoclonal antibodies (mAbs) to overcome this immunosuppressive TME...RT amplifies ICPIL2ZA effectiveness by inducing NKG2D ligands on tumor cells, facilitating immune infiltration that leads to tumor growth control and extends survival without apparent toxicity. These results suggest that ICPIL2ZA can overcome limitations of traditional therapies by augmenting antitumor capabilities of endogenous immune cells, highlighting a promising autologous strategy for PDAC and other immunologically "cold" tumors."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • NKG2D

Effect of metformin on inflammation and bone damage in a rat model of medication-related osteonecrosis of the jaw. (PubMed, Eur J Oral Sci) - "This study investigated how chronic metformin administration modulates the cellular profile and inflammatory markers in a zoledronic acid-based rat model of medication-related osteonecrosis of the jaw (MRONJ). Metformin also reduced the myeloperoxidase activity and decreased IL-1β levels in vitro. In conclusion, metformin reduced the severity of MRONJ by mitigating the inflammatory response."

Journal • Preclinical • Inflammation • IL1B • MPO • TRAP