Treatment depends on the severity of symptoms and the underlying cause. [28]
Volume depletion results from uncontrolled symptoms leading to decreased intake and enhanced renal sodium loss. This tends to exacerbate or perpetuate the hypercalcemia by increasing Na+ reabsorption in the thick ascending limb of the loop of Henle (TALH). Thus, appropriate volume repletion with isotonic sodium chloride solution is an effective short-term treatment for hypercalcemia. [29]
Once volume is restored, simultaneous administration of loop diuretics blocks Na+ and calcium reabsorption in the TALH. Replacing ongoing sodium, potassium, chloride, and magnesium losses is important if prolonged sodium chloride and loop diuretic therapy is contemplated.
Immobilization aggravates hypercalcemia. Whenever possible, weightbearing mobilization should be encouraged.
Reduction of dietary calcium and vitamin D intake is effective for treating hypercalcemia due to increased intestinal calcium absorption (eg, in idiopathic infantile hypercalcemia). In vitamin D toxicity or extrarenal synthesis of 1,25(OH) D3 (eg, in sarcoidosis), prednisone may help to reduce plasma calcium levels by reducing intestinal calcium absorption. Oral phosphate also can be used to form insoluble calcium phosphate in the gut.
Peritoneal dialysis or hemodialysis against calcium-free or lower–calcium-concentration dialysate solution is highly effective in lowering plasma calcium levels.(Indeed, hydration is ineffective in patients with kidney failure, because diuresis is impossible; Dialysis is necessary to correct hypercalcemia in patients with renal failure.)
Bisphosphonates inhibit osteoclastic bone resorption and are effective in the treatment of hypercalcemia due to conditions causing increased bone resorption and malignancy-related hypercalcemia. Pamidronate and etidronate can be given intravenously, while risedronate and alendronate may be effective as oral therapy.
Calcitonin can be given intramuscularly or subcutaneously, but it becomes less effective after several days of use. The antineoplastic antibiotic mithramycin blocks osteoclastic function and can be given for severe malignancy-related hypercalcemia. It has significant hepatic, renal, and marrow toxicity.
The US Food and Drug Administration (FDA) approved denosumab for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy, in December 2014. [30] Approval was based on results from an open-label, single-arm study that enrolled patients with advanced cancer and persistent hypercalcemia after recent bisphosphonate treatment.
The study achieved its primary endpoint with a response rate at day 10 of 63.6% in the 33 patients evaluated. The estimated median time to response (albumin-corrected serum calcium < 11.5 mg/dL [2.9 mmol/L]) was 9 days, and the median duration of response was 104 days. [31]
Guidelines on adults with hypercalcemia of malignancy, published in 2022 by the Endocrine Society, recommend intravenous (IV) hydration and IV bisphosphonate or denosumab for hypercalcemia of malignancy in adults; the guidelines conditionally recommend treatment with denosumab over IV bisphosphonate for acute hypercalcemia of malignancy. [32]
The same guidelines conditionally recommend combination therapy with calcitonin and IV bisphosphonate or denosumab for adults with severe hypercalcemia of malignancy (serum calcium level >14 mg/dL). [32]
In addition, the guidelines conditionally recommend denosumab for adults who, despite being treated with IV bisphosphonate, have refractory or recurrent hypercalcemia of malignancy. Further, they conditionally state that calcimimetic and/or antiresorptive therapy can be used to treat patients with parathyroid carcinoma–associated hypercalcemia, depending on the hypercalcemia’s severity and the results of initial treatment. [32]
Surgical care is directed toward reversing the underlying cause of hypercalcemia or repairing the orthopedic damage, as follows [33, 34] :
Consultation with a surgeon or orthopedist may be required, as indicated.
