Abstract
Malignancy-associated hypercalcemia (MAH) is the commonest cause of hypercalcemia in hospitalized patients. Its incidence is 15 cases per 100,000 person-year. Such complication develops in almost 10% of patients with advanced cancer representing, ultimately, the most frequent cause of death in several patients with cancer. Parathyroid hormone related protein (PTHrP), which has strong homology to parathyroid hormone, is the commonest hormonal mediator of MAH. Overall, about 80% of patients with MAH have increased PTHrP serum levels. Bisphosphonates are synthetic analogues of pyrophosphate, and represent the principal support of treatment. Several bisphosphonates have shown to decrease serum calcium levels by inhibiting PTH-dependent osteoclast activation. They are potent and effective inhibitors of osteoclast-mediated bone resorption, and have shown antiangiogenic properties in some experimental models. At present, pamidronate, zoledronate and ibandronate should be considered the drugs of choice in the treatment of MAH. Old agents such as mithramycin, calcitonine, and gallium nitrate have practically been abandoned due to their limited activity and huge side effects, especially for the kidney. A new experimental approach to MAH involves the blockade of receptor activator of nuclear factorkappa B ligand, usually abbreviated as RANKL. RANKL is a key element in the differentiation, function, and survival of osteoclasts, which plays an essential role in removing Ca ++ from the bone in response to PTH stimulation. This review provides information about the actual medical treatment of MAH.
Keywords: Malignancy-associated syndrome, hypercalcemia, bisphosphonates, parathyroid hormone related protein, PTHrP, cancer therapy, paraneoplastic syndrome, malignancy
Current Medicinal Chemistry
Title: Medical Treatment of Malignancy-Associated Hypercalcemia
Volume: 15 Issue: 4
Author(s): F. Lumachi, A. Brunello, A. Roma and U. Basso
Affiliation:
Keywords: Malignancy-associated syndrome, hypercalcemia, bisphosphonates, parathyroid hormone related protein, PTHrP, cancer therapy, paraneoplastic syndrome, malignancy
Abstract: Malignancy-associated hypercalcemia (MAH) is the commonest cause of hypercalcemia in hospitalized patients. Its incidence is 15 cases per 100,000 person-year. Such complication develops in almost 10% of patients with advanced cancer representing, ultimately, the most frequent cause of death in several patients with cancer. Parathyroid hormone related protein (PTHrP), which has strong homology to parathyroid hormone, is the commonest hormonal mediator of MAH. Overall, about 80% of patients with MAH have increased PTHrP serum levels. Bisphosphonates are synthetic analogues of pyrophosphate, and represent the principal support of treatment. Several bisphosphonates have shown to decrease serum calcium levels by inhibiting PTH-dependent osteoclast activation. They are potent and effective inhibitors of osteoclast-mediated bone resorption, and have shown antiangiogenic properties in some experimental models. At present, pamidronate, zoledronate and ibandronate should be considered the drugs of choice in the treatment of MAH. Old agents such as mithramycin, calcitonine, and gallium nitrate have practically been abandoned due to their limited activity and huge side effects, especially for the kidney. A new experimental approach to MAH involves the blockade of receptor activator of nuclear factorkappa B ligand, usually abbreviated as RANKL. RANKL is a key element in the differentiation, function, and survival of osteoclasts, which plays an essential role in removing Ca ++ from the bone in response to PTH stimulation. This review provides information about the actual medical treatment of MAH.
Export Options
About this article
Cite this article as:
Lumachi F., Brunello A., Roma A. and Basso U., Medical Treatment of Malignancy-Associated Hypercalcemia, Current Medicinal Chemistry 2008; 15 (4) . https://dx.doi.org/10.2174/092986708783497346
DOI https://dx.doi.org/10.2174/092986708783497346 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Short-Term Intra-Nasal Erythropoietin Administration with Low Sialic Acid Content is without Toxicity or Erythropoietic Effects
Current Neurovascular Research Vitamin D and Vascular Disease
Current Vascular Pharmacology Recent Applications of Doebner, Doebner-von Miller and Knoevenagel-Doebner Reactions in Organic Syntheses
Current Organic Synthesis Actin and Keratin are Binding Partners of the 1,25D<sub>3</sub>-MARRS Receptor/PDIA3/ERp57
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Obesity and Asthma
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Effects of Hyperlipidemia and Cardiovascular Diseases on Proliferation, Differentiation and Homing of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Advances in Osteoclast Differentiation and Function
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications
Current Drug Targets Beneficial Effects of Selective Vitamin D Receptor Activation by Paricalcitol in Chronic Kidney Disease
Current Drug Targets Bone Tissue Regeneration - Application of Mesenchymal Stem Cells and Cellular and Molecular Mechanisms
Current Stem Cell Research & Therapy Disorder in Milk Proteins: Formation, Structure, Function, Isolation and Applications of Casein Phosphopeptides
Current Protein & Peptide Science Differential Proteomic Identification and Bioinformatics Analysis of Femoral Neck in Elderly Female Patients with Hyperuricaemia
Current Proteomics Detection and Transport Mechanisms of Circulating microRNAs in Neurological, Cardiac and Kidney Diseases
Current Medicinal Chemistry Computational Approaches for the Identification and Optimization of Src Family Kinases Inhibitors
Current Medicinal Chemistry microRNA in Chondrogenesis, Cartilage and Osteoarthritis
Current Rheumatology Reviews The Role of Insulin-Like Growth Factor I Components in the Regulation of Vitamin D
Current Pharmaceutical Biotechnology Bioadhesive Films as Drug Delivery Systems
Drug Delivery Letters Is There An Association Between Vitamin D and Hypertension?
Recent Patents on Cardiovascular Drug Discovery Vitamin D and Cardiovascular Disease: A Novel Agent for Reducing Cardiovascular Risk?
Current Vascular Pharmacology The Current Role and Therapeutic Targets of Vitamin D in Gastrointestinal Inflammation and Cancer
Current Pharmaceutical Design