What is the role of PTH-related protein (PTHrP) in the etiology of hypercalcemia?

Updated: Dec 03, 2020
  • Author: Mahendra Agraharkar, MD, MBBS, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Hypercalcemia caused by a neoplasm tends to be much more serious. The mechanism of hypercalcemia in malignancy can be from the ectopic production of a PTH-like factor, PTH-related protein (PTHrP), or osteolytic metastases. Cancers that produce PTHrP include breast cancer, lung cancer, prostate cancer, and multiple myeloma. [15]

PTHrP increases the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in bone. RANKL in turn contributes to the development of hypercalcemia by binding to receptor activator of nuclear factor kappa B (RANK) on the surface of osteoclast precursors, leading to bone osteolysis.

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