Medical treatment of malignancy-associated hypercalcemia

F. Lumachi, A. Brunello, A. Roma, U. Basso

Research output: Contribution to journalArticlepeer-review


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 MAE 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 factor-kappa 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.

Original languageEnglish
Pages (from-to)415-421
Number of pages7
JournalCurrent Medicinal Chemistry
Issue number4
Publication statusPublished - Feb 2008


  • Bisphosphonates
  • Cancer therapy
  • Hypercalcemia
  • Malignancy
  • Malignancy-associated syndrome
  • Paraneoplastic syndrome
  • Parathyroid hormone related protein
  • PTHrP

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Organic Chemistry
  • Pharmacology


Dive into the research topics of 'Medical treatment of malignancy-associated hypercalcemia'. Together they form a unique fingerprint.

Cite this