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Berardi et al. J Cancer Metastasis Treat 2019;5:79 I http://dx.doi.org/10.20517/2394-4722.2019.008 Page 13 of 33

Figure 3. Algorithm of hypocalcemia management [48,78-86] . For a correct diagnostic classification of hypocalcemia, it is essential to
distinguish between hypoparathyroidism and other causes through the dosage of blood parathyroid hormone. In the case of high
parathormone concentrations, dosage of vitamin D is useful to exclude deficiency. PTH: parathyroid hormone

In the case of hypoparathyroidism, the treatment aims to control symptoms, maintaining adequate
serum calcium levels (2.00-2.12 mmol/L), and a calcium-phosphate ratio below 4.4 mmol/L, in order to
[81]
prevent hypercalciuria and precipitation of calcium salts in soft tissues . Calcitriol, a vitamin D analog, is
usually used with a starting dose of 0.5 mcg/day, which might be increased until adequate serum calcium
[82]
concentrations are reached. Thiazide diuretics associated with a low phosphate diet could be considered .
It is recommended to monitor weekly serum calcium, phosphorus concentration, and creatinine during
[83]
initial administration to obtain a correct stabilization of the dose .
In the case of chronic hypocalcemia, oral supplementation of calcium (calcium carbonate or calcium
[84]
citrate) and vitamin D is recommended. In the case of hypomagnesemia, it should be corrected .
Vitamin D insufficiency requires supplementation with oral or intramuscular ergocalciferol (vitamin D2)
or oral cholecalciferol (vitamin D3). When hypocalcemia is secondary to vitamin D malabsorption, it is
important to correct the underlying cause (e.g., celiac patients should receive a gluten-free diet) .
[85]
Patients receiving bisphosphonates or anti-RANKL should receive oral calcium and vitamin D
[86]
supplementation to prevent hypocalcemia .

Hypercalcemia
Definition and clinical implication
[87]
Hypercalcemia is defined as a higher serum calcium concentration (total serum calcium over than 10.5 mg/dL) .
It is a common electrolyte disorder in patients with advanced malignancies and it correlates with poor
[88]
prognosis .
Causes
Several causes might contribute to the development of hypercalcemia in cancer patients [Table 4]:
(1) Cancer: the main cause of hypercalcemia in cancer patients is hyperparathyroidism. It can be divided