Interaction of serum calcium with serum phosphorus important with hypercalcemia - DVM
News Center
DVM Featuring Information from:


Interaction of serum calcium with serum phosphorus important with hypercalcemia

DVM InFocus

Vitamin D toxicosis can result from oversupplementation with vitamin D3, ingestion of plants containing calcitriol glycosides, cholecalciferol rodenticide exposure and calcipotriol (Dovonex, United States and Canada; Daivonex, Europe human anti-psoriatic cream). Nonmalignant skeletal lesions include osteomyelitis (bacterial/fungal), hypertrophic osteodystrophy (HOD) and disuse osteoporosis (immobilization).

Other causes of hypercalcemia may include excessive use of intestinal phosphate binders, excessive calcium supplementation (calcium carbonate), hypervitaminosis A, milk-alkali syndrome, thiazide diuretics, acromegaly, thyrotoxicosis, postrenal transplantation and aluminum exposure.

In hypercalcemic dogs, neoplasia is the most common underlying diagnosis, followed by hypoadrenocorticism, primary hyperparathyroidism and chronic renal failure. Approximately 70 percent of hypercalcemic dogs are also azotemic. Azotemia is uncommon only in dogs with hyperparathyroidism. In hypercalcemic cats, renal failure is most commonly associated with hypercalcemia, occurring in 38 percent of cats with hypercalcemia. Neoplasia is the second most common cause of hypercalcemia, with 33 percent diagnosed with lymphosarcoma, 33 percent with squamous cell carcinoma, and the remaining diagnosed with leukemia, osteosarcoma, fibrosarcoma, undifferentiated sarcoma and bronchogenic carcinoma. Calcium oxalate urolithiasis is noted in about 15 percent of all cats with hypercalcemia.

In cats, the frequency of hypercalcemia without obvious explanation is increasing in clinical practice. Total serum calcium concentration is increased, often without obvious clinical signs, for months to more than one year. Serum ionized calcium concentration is increased, sometimes out of proportion to the degree of increase in total serum calcium concentration. Nephrocalcinosis may be observed on abdominal radiographs or renal ultrasonography, but renal function based on BUN and serum creatinine concentrations initially is normal.

Chronic renal failure eventually develops in most of these cats. Challenge with prednisone therapy results in long-term decreases in serum ionized and total serum calcium concentrations in some cats.

Treatment Whether to institute aggressive treatment directed against hypercalcemia depends largely on the severity of presenting signs, regardless of the specific level of hypercalcemia. The trend in magnitude of hypercalcemia plays a role in this decision, as rapidly rising hypercalcemia justifies more aggressive intervention.

There is no absolute serum calcium concentration that can be used as a guideline for the decision to treat aggressively. Removal of the underlying cause is always the definitive treatment for hypercalcemia. Complete excision of isolated tumors will abolish hypercalcemia, and in animals with disseminated metastases, multicentric neoplasia, or nonresectable primary malignancy, tumor burden and hypercalcemia may be decreased by appropriate chemotherapy, radiation therapy, and immunotherapy. Supportive therapy is often necessary to decrease serum calcium concentration to less toxic levels.

Parenteral fluids, furosemide, glucocorticosteroids or combinations of these treatments will effectively reduce serum calcium concentrations in most animals with hypercalcemia. Normal saline solution (0.9% NaCl) is the preferred fluid solution for correction of intravascular volume deficit and for further mild volume expansion. Potassium supplementation is often necessary to maintain normal serum potassium concentration during extended periods of fluid treatment.

Furosemide follows rehydration and fluid volume expansion and is importance for treatment of persistent hypercalcemia. Furosemide (5 mg/kg initial intravenous bolus dose followed by 5 mg/kg per hour infusion) can be helpful in acutely decreasing serum calcium concentration by a maximum of about 3 mg/dl. Less aggressive regimens of furosemide administration may be effective in combination with other treatments or for chronic management of hypercalcemia.

Glucocorticosteroids can significantly reduce the magnitude of persistent hypercalcemia in animals with lymphosarcoma, multiple myeloma, hypoadrenocorticism, hypervitaminosis D, or granulomatous disease, but glucocorticosteroids have little effect on other causes of hypercalcemia.

Several therapeutic modalities concomitantly are often needed in these cases. Diphosphonates assist in lowering serum calcium concentration. Etidronate disodium (Didronel; 5-15 mg/kg daily to twice daily) is a first-generation compound that is not well-absorbed orally but still is useful. Pamidronate disodium (Aredia; 1.3 mg/kg in 150 ml 0.9% saline solution in a two-hour intravenous infusion and can be repeated in one to three weeks) and risedronate (Actonel) are new-generation bisphosphonates that may be more effective than etidronate disodium. Calcitonin is an antidote for cholecalciferol rat poison but may be useful in other cases in which bone resorption is the primary cause of hypercalcemia.

Calcitonin treatment is expensive, effects may be short-lived as in hours, and the magnitude of its effect is unpredictable. Mithramycin (25 mcg/kg intravenous in 5% dextrose and water solution over two to four hours every two to four weeks) has also been shown to decrease serum calcium levels for several days, though extreme caution must be used to properly infuse low doses over several hours to reduce renal and hepatic toxicities.

Low calcium diets are only helpful in substantially lowering serum calcium concentration in hypercalcemia caused by the action of excess vitamin D metabolites.


Source: DVM InFocus,
Click here