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Journal Scan

April 2017

Disturbance of blood calcium homeostasis in cancer patients

Summarized from Body JJ, Niepel D, Tonini G. Hypercalcemia and hypocalcemia: finding the balance. Support Care Cancer 2017 doi:10.1007/s00520-016-3543-1 Available online (12th Jan2017) ahead of print
In health plasma ionized calcium concentration (iCa) is maintained within the approximate reference range of 1.15-1.30 mmol/L (4.6-5.2 mg/dL) principally by the synergistic action of two hormones: parathyroid hormone (PTH) and the vitamin D-derived hormone, calcitriol. 

Hypercalcemia (increased blood calcium), defined as iCa > 1.30 mmol/L (5.2 mg/dL) and hypocalcemia (decreased blood calcium) defined as iCa < 1. 15 mmol/L (4.6 mg/dL) are common electrolyte disturbances, which if sufficiently severe, have major symptomatic effect, including potentially fatal cardiac arrhythmia. 

Of the many possible causes of hypercalcemia, malignant disease (cancer) is the most common. This so-called “hypercalcemia of malignancy” is the principal focus of a recently published review article. 

Hypercalcemia of malignancy has its origins in bone, so it is appropriate that the article begins with brief discussion of the contribution that bone metabolism makes to the maintenance of normal blood calcium levels.

This highlights the quite normal constant remodeling of bone due to the opposing action of two bone-cell types: osteoblasts (bone-forming cells) and osteoclasts (bone-resorption cells).

Osteoblastic activity is associated with movement of calcium from blood to bone (for the process of bone formation) whilst osteoclastic activity is associated with movement of calcium from bone to blood, as bone is resorbed.

The maintenance of normal plasma calcium concentration thus depends to a large degree on the continuing hormonal-controlled balance between bone formation and bone resorption. 

The article continues with discussion of the way in which a number of factors elaborated from tumor cells can disrupt this normal balance of bone metabolism through modulation of osteoblast and osteoclast function, with resulting excessive movement of calcium from bone to blood, and consequent hypercalcemia. 

Other topics discussed include: incidence/prevalence of hypercalcemia in cancer patients; the cancer types most frequently associated with hypercalcemia (breast, lung, hematological); the significance of metastatic spread of tumor cells to bone; the poor prognosis associated with development of hypercalcemia in cancer patients; and the symptoms of hypercalcemia.

A relatively large part of the article is devoted to discussion of the treatment of hypercalcemia of malignancy. The main focus here is the bisphosphonates, a group of drugs that reduce plasma calcium by inhibiting bone resorption. Recent trials comparing the efficacy of different bisphosphonates (clodronate, pamidronate, ibandronate and zoledronic acid) are considered. 

The final section of this article moves away from its main focus (hypercalcemia) and addresses the issue of hypocalcemia in cancer patients. The authors describe a mechanism for the development of bone-resorption-induced hypocalcemia that can occur in patients with prostate cancer, particularly those whose cancer has spread beyond the prostate to bone.

But the emphasis here is on the hypocalcemia that sometimes occurs in the generality of cancer patients because of the calcium-lowering drugs (bisphosphonates) they are given to combat either hypercalcemia or the effects of metastatic bone disease (bone pain, fracture, etc.).

Treatment of hypocalcemia (calcium and vitamin D supplements) is discussed, and the authors emphasize the importance of plasma calcium monitoring of cancer patients receiving bisphosphonates to prevent/identify hypocalcemia.  

The article draws on 91 cited references. 

May contain information that is not supported by performance and intended use claims of Radiometer's products. See also Legal info.

Chris Higgins

has a master's degree in medical biochemistry and he has twenty years experience of work in clinical laboratories.

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