ArticleJournal for immunotherapy of cancer2024
Favorable impact of PD1/PD-L1 antagonists on bone remodeling: an exploratory prospective clinical study and ex vivo validation.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The effect of radiotherapy, chemotherapy, and immunotherapy on fusion rate in spinal surgery using osteobiologics for patients with metastatic spinal disease: a systematic review.Neurosurgical review · 2024Pooled it
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Biologic immunomodulators and spinal fusion: evidence, mechanisms, and perioperative considerations.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Immune Checkpoint Inhibitors and Bone Health: Mechanisms, Clinical Implications, and Emerging Perspectives on Bone Fragility.Current osteoporosis reports · 2026Review
- Bone Adverse Events in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy: A Comprehensive Review of the Literature from the Clinical Action Group of the European Calcified Tissue Society.Calcified tissue international · 2026Review
- Programmed cell death protein 1 (PD-1) blockade regulates skeletal remodeling in a sex- and age-dependent manner.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Assessing the effects of immune checkpoint inhibitors on bone utilizing machine learning-assisted opportunistic quantitative computed tomography.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Article
- Tumor microenvironment and immune-related myositis: addressing muscle wasting in cancer immunotherapy.Frontiers in immunology · 2025Review
- The regulatory effects of PD-1/PD-L1 inhibitors on bone metabolism: opportunities and challenges in osteoporosis management.Frontiers in immunology · 2025Review
- Immune-related osteoblastic bone alterations mimicking bone metastasis in a small-cell lung cancer patient treated with durvalumab: a case report.Translational lung cancer research · 2024Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSkeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment strategies. Despite their widespread use in early disease stages, the effects of immune checkpoint inhibitors (ICIs) on the skeleton are still poorly defined. Here, we initiated a comprehensive investigation of the impact of ICIs on bone health by longitudinal assessment of bone turnover markers in patients with cancer and by validation in a novel bioengineered 3D model of bone remodeling.
methodsAn exploratory longitudinal study was conducted to assess
resultsDuring the first month of treatment, CTX levels decreased sharply but transiently. In contrast, we observed a delayed increase of serum levels of PINP and OCN after 4 months of therapy. In vitro, ICIs impaired the maturation of preosteoclasts by inhibiting STAT3/NFATc1 signaling but not JNK, ERK, and AKT while lacking any direct effect on osteogenesis. However, using our bioengineered 3D bone model, which enables the simultaneous differentiation of OB and OC precursor cells, we confirmed the uncoupling of the OC/OB activity on exposure to ICIs by demonstrating impaired OC maturation along with increased OB differentiation.
conclusionOur study indicates that the inhibition of the PD1/PD-L1 signaling axis interferes with bone turnover and may exert a protective effect on bone by indirectly promoting osteogenesis.
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