- Author: Mahendra Agraharkar, MD, MBBS, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
The first therapy for symptomatic hypercalcemia is volume repletion. More severe cases require saline infusion with concomitant loop diuretics (eg, furosemide) to increase calcium excretion and lower levels rapidly. Other therapies, outlined below, are for longer-term management. Note, however, that no current therapies generally are effective for long-term outpatient therapy. Definitive treatment often requires surgical management of the underlying cause.
Bisphosphonates are effective in the treatment of malignancy-related hypercalcemia and hypercalcemia due to conditions causing increased bone resorption. Zoledronic acid is 100-850 times more potent than pamidronate and may be given as a bolus rather than an infusion. Clodronate (not available in the United States) can be given either intravenously or orally and may represent a better alternative in the future. The monoclonal antibody denosumab is approved for the treatment of hypercalcemia of malignancy that is refractory to bisphosphonate therapy.
Inhibit bone reabsorption.
Used after initial hydration to inhibit bone reabsorption and maintain low serum calcium levels, especially in hypercalcemia of malignancy and Paget disease.
Reduces bone formation and does not alter renal tubular reabsorption of calcium. Does not affect hypercalcemia in patients with hyperparathyroidism.
Available in the United States, but not yet indicated for treatment of hypercalcemia; alendronate probably is useful for long-term prevention of recurrence of hypercalcemia following use of more conventional therapy (ie, hydration and pamidronate). Useful in preventing and treating osteoporosis, which is a complication of prolonged mild hypercalcemia.
Monoclonal Antibodies, Endocrine
Binds RANKL and thereby prevents osteoclast formation resulting in decreased bone resorption and decreased calcium release from bone.
Denosumab is a monoclonal antibody that specifically targets RANKL. It binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption, thereby modulating calcium release from bone. It is indicated for hypercalcemia of malignancy refractory to bisphosphonate therapy.
Antidote, hypercalcemia agents
Inhibit bone resorption and increase renal calcium excretion.
Lowers elevated serum calcium in patients with multiple myeloma, carcinoma, or primary hyperparathyroidism. Expect higher response when serum calcium levels are high.
Onset of action is approximately 2 h following injection, and activity lasts for 6-8 h. May lower calcium levels for 5-8 d by approximately 9% if given q12h. IM route is preferred at multiple injection sites with dose > 2 mL.
Inhibit cytokine release and have a direct cytolytic effect on some tumor cells.
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Phosphate inhibits calcium absorption and promotes calcium deposition. Theorized to help bind dietary calcium, thus rendering it an unabsorbable calcium-phosphorous product, but used rarely.
Increases urinary pyrophosphate and complexes with calcium, thus decreasing urinary calcium level, while pyridoxine results in a reduction of urinary oxalate excretion. All dosage forms must be mixed in 6-8 oz of water. Never give IV. Never give if renal function is abnormal or if serum phosphorous levels are > 3 mg/dL.
Binds to and modulates the parathyroid calcium-sensing receptor, increases sensitivity to extracellular calcium, and reduces parathyroid hormone secretion.[1, 14]
Marcocci et al performed an open-label, single-arm study to determine how effectively cinacalcet, a calcimimetic, reduces hypercalcemia in patients with intractable persistent primary hyperparathyroidism. The investigation, performed on 17 patients, included a 2- to 16-week titration phase and a maintenance phase of up to 136 weeks. By the end of the titration phase, serum calcium had been reduced in 15 patients by at least 1 mg/dL. Although 15 patients suffered adverse events related to treatment (most commonly, nausea, vomiting, and paresthesias), none of these were considered to be serious.
Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium-sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and in hypercalcemia with parathyroid carcinoma.
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