Hypercalcemia in Cancer Pathophysiology and Management
Summary
Hypercalcemia is a common and potentially life‐threatening complication of malignancy, arising in up to 40 percent of patients with advanced neoplasms. It results from tumour‐driven disruptions in calcium homeostasis, most notably via parathyroid hormone-related peptide (PTHrP) secretion, osteoclast activation at sites of bone metastasis, ectopic production of calcitriol and, rarely, true parathyroid hormone (PTH) secretion. Elevated serum calcium impairs neuromuscular, cardiovascular and renal function, producing symptoms that range from fatigue and polyuria to arrhythmia and renal failure. Initial management focuses on aggressive intravenous hydration to enhance renal calcium excretion, followed by antiresorptive therapies—principally bisphosphonates or the RANK ligand inhibitor denosumab—to suppress osteoclast‐mediated bone resorption. Adjunctive agents such as calcitonin and glucocorticoids may be employed in specific contexts, for example calcitriol-mediated hypercalcemia. Optimal long-term control demands concurrent treatment of the underlying malignancy, multidisciplinary coordination and, increasingly, the integration of novel targeted agents that interrupt tumoral calcium‐regulating pathways.
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Hypercalcemia in Cancer Pathophysiology and Management publication trend
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Technical terms
Parathyroid hormone-related peptide (PTHrP): A tumoral protein analogue of PTH that stimulates osteoclasts and renal calcium reabsorption, driving humoral hypercalcemia of malignancy.
Humoral hypercalcemia of malignancy (HHM): Elevated serum calcium caused by circulating factors (chiefly PTHrP) secreted by neoplastic cells at sites distant from bone metastases.
Osteoclast: A specialised bone cell responsible for bone matrix degradation, releasing calcium and phosphate into the circulation.
Bisphosphonates: Pharmacological inhibitors of osteoclast activity that reduce bone resorption and lower serum calcium levels.
Denosumab: A monoclonal antibody targeting RANK ligand to prevent maturation and activity of osteoclasts, used when bisphosphonates are contraindicated or ineffective.
Calcitriol (1,25-dihydroxyvitamin D): The active form of vitamin D that increases intestinal calcium absorption and may be produced ectopically by some tumours.
References
- Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies. Cells (2024).
- Cancer-related hypercalcemia and potential treatments. Frontiers in Endocrinology (2023).
- Prevalence of hypercalcemia among cancer patients in the United States. Cancer Medicine (2016).
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