RANK ligand and osteoprotegerin in myeloma bone disease.
Open accessAbstract
Myeloma bone disease is due to interactions of myeloma cells with the bone marrow microenvironment, and is associated with pathologic fractures, neurologic symptoms and hypercalcemia. Adjacent to myeloma cells, the formation and activation of osteoclasts is increased, which results in enhanced bone resorption. The recent characterization of the essential cytokine of osteoclast cell biology, receptor activator of NF-κB ligand (RANKL) and its antagonist osteoprotegerin (OPG), have led to a detailed molecular and cellular understanding of myeloma bone disease. Myeloma cells induce RANKL expression in bone marrow stromal cells, and direct RANKL expression by myeloma cells may contribute to enhanced osteoclastogenesis in the bone microenvironment in myeloma bone disease. Furthermore, myeloma cells inhibit production and induce degradation of OPG. These effects result in an increased RANKL-to-OPG ratio that favors the formation and activation of osteoclasts. Patients with myeloma bone disease have inappropriately low serum and bone marrow levels of OPG. Specific blockade of RANKL prevented the skeletal complications in various animal models of myeloma, and suppressed bone resorption in a preliminary study of patients with myeloma bone disease.
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Prostate cancer cells and multiple myeloma cells express RANKL directly.
“prostate cancer cells (CaP) (314 -316) and MM cells (317-322) have been shown to express RANKL directly.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [322]
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References 58 · Cited by 258
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- Authors
- Sezer, O., Heider, U., Zavrski, I., Kühne, C. A., & Hofbauer, L. C.
- Affiliations
- Philipps University of Marburg (DE)
- From the Department of Oncology and Hematology, Universitätsklinikum Charité, Berlin, Germany; the Department of Trauma Surgery, University of Essen, Essen, Germany; and the Division of Gastroenterology, Endocrinology and Metabolism, Philipps University, Marburg, Germany.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-03-15
- Volume
- 101
- Issue
- 6
- Pages
- 2094-2098
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1996560056
- Cited by
- 258
- References
- 58
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 5 · 2013: 10 · 2012: 9
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- myeloma bone disease, RANK ligand, osteoprotegerin, osteoclastogenesis, bone resorption, bone marrow microenvironment, mesenchymal stem cells, RANKL blockade, hypercalcemia, pathological fracture, multiple myeloma
- MeSH terms
- Animals, Bone Neoplasms, Carrier Proteins, Glycoproteins, Humans, Membrane Glycoproteins, Multiple Myeloma, Osteoblasts, Osteoclasts, Gene Expression, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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