Hypercalcemia of Malignancy

  • John W. Jacobs
  • Ellen Simpson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 208)


Hypercalcemia is frequently associated with malignant disease (Stewart et al, 1980, Mundy et al, 1984). The primary underlying cause is an increase in osteoclastic bone resorption but the mechanisms which lead to this increase are still the focus of current research. A number of investigators have utilized different approaches to identify factors which are secreted from tumors associated with hypercalcemia and which are responsible for increased bone resorption. It is now apparent that different classes of protein factors are responsible for the hypercalcemia observed in different types of malignancies. For example, in patients with myeloma the lymphokine, osteoclast-activating factor, is most likely the humoral factor secreted from myeloma cells and causing bone resorption (Mundy et al, 1974). Hypercalcemia can also occur in patients who have solid tumors without bone metastases and bone resorption in this type of hypercalcemia is often associated with hypophosphatemia and an increase in nephrogenous cyclic AMP excretion (Stewart et al, 1980).


Epidermal Growth Factor Receptor Bone Resorption Parathyroid Hormone Translation Product Osteoclastic Bone Resorption 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Breslau, N.A., McGuire, J.L., Zerwekh, J.E., Frenkel, E.P., and Pak, C.Y.C., 1974, Hypercalcemia associated with increased serum calcitriol levels in three patients with lymphoma, Annals Int Med 100: 1.Google Scholar
  2. Ibbotson, K.J., Twardzik, D.R., D’Souza, S.M., Hargreaves, W.R., Todaro, G.J., and Mundy, G.R., 1985, Stimulation of bone resorption in vitro by synthetic transforming growth factor-alpha, Science 228: 1007.CrossRefGoogle Scholar
  3. Klein, R.F., Strewler, G.J., Nissenson, R.A., Williams, R.D., and Leung, S.C., June, 1985, PTH-like protein from human carcinoma cells stimulates bone resorption, Abstract 145, 7th Annual Am Soc Bone and M in Res.Google Scholar
  4. Mundy, G.R., Raisz, L.G., Cooper, R.A., Schechter, G.P., and Salmon, S.E., Evidence for the secretion of an osteoclast stimulating factor in myeloma. N Engl J Med 291: 1041, 1974.CrossRefGoogle Scholar
  5. Mundy, G.R., Ibbotson, K.J., D’Souza, S.M., Simpson, E.L., Jacobs, J.W., and Martin, T.J., 1984, The hypercalcemia of cancer: Clinical implications and pathogenic mechanisms, New Engl J Med 310:1718.CrossRefGoogle Scholar
  6. Raisz, L.G., 1975, Epidermal growth factor resorbes bone in vitro, J Clin Invest 44: 103.Google Scholar
  7. Rodan, S.B., Insogna, K.L., Vignery, A. M-C., Stewart, A.F., Broadus, A.E., D’Souza, S.M., Bertolini, D.R., Mundy, G.R., and Rodan, G.A., 1983, Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells, J Clin Invest 72: 1511.CrossRefGoogle Scholar
  8. Simpson, E., Mundy, G.R., Ibbotson, K., D’Souza, S., Jacobs, J., 1983, Absence of parathyroid hormone messenger RNA in nonparathyroid tumors associated with hypercalcemia, N Engl J Med 309: 325.CrossRefGoogle Scholar
  9. Stewart, A.F., Horst, R., Deftos, L.J., Cadman, E.C., Lang, R., and Broadus, A.E., 1980, Biochemical evaluation of patients with cancer associated with hypercalcemia: evidence for humoral and non-humoral groups, N Engl J Med 303: 1377.CrossRefGoogle Scholar
  10. Stewart, A.F., Insogna, K.L., Goltzman, D., and Broadus, A.B., 1983, Identification of adenylate cyclase stimulating activity and cytochemical glucose 6 phosphate dehydrogenase stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy, PNAS 80: 1454.Google Scholar
  11. Strewler, G.J., Williams, R.D., and Nissenson, R.A., 1983, Human renal carcinoma cells produce hypercalcemia in the nude mouse and a novel protein recognized by parathyroid hormone receptors, J Clin Invest 71: 769.CrossRefGoogle Scholar
  12. Tashjian, A.H., Voelkel, B.F., Lazzaro, M., Singer, F.R., Roberts, A.B., Derynck, R., Winkler, M.B., and Levine L., 1985, Alpha and Beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria, Proc Natl Acad Sci 82: 4535–4538.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • John W. Jacobs
    • 1
  • Ellen Simpson
    • 1
  1. 1.Biological ChemistryMerck Sharp & Dohme Research LaboratoriesWest PointUSA

Personalised recommendations