Title:Treatment of Chronic Hypercalcemia
Volume: 8
Issue: 4
Author(s): Valentina Camozzi, Giovanni Luisetto, Stefano M.M. Basso, Piero Cappelletti, Renato Tozzoli and Franco Lumachi
Affiliation:
Keywords:
Hypercalcemia, hyperparathyroidism, bisphosphonates, RANKL, PTHrP, parathyroidectomy, Zoledronate, denosumab, loop diuretics, concomitant natriuretic
Abstract: Hypercalcemia is a relatively frequent alteration, mostly associated to primary hyperparathyroidism (PHPT)
and malignancy-associated hypercalcemia (MAH). Treatment first includes rehydration and loop diuretics, as general
measures. Bisphosphonates are considered the drugs of choice due to their long-term management. Calcitonin is preferable
in the short-term control of severe hypercalcemia. The antireabsorptive action of bisphosphonates has been considered
the most effective in the disorders characterized by an excessive bone resorption. Zoledronate is superior to both clodronate
or pamidronate in the treatment of MAH. Calcimimetic agents has been recently introduced to control hypercalcemia
in selected cases of PHPT. They are used when surgery is not possible or patients do not meet surgical criteria. Malignancy-
associate hypercalcemia is broadly divided into two categories: humoral MAH and osteolytic MAH. The first
concerns the paraneoplastic release of humoral factors, mainly parathyroid hormone-related peptide (PTHrP). Recently a
humanized monoclonal antibody against human PTHrP has been generated and is still under evaluation. The receptor activator
of nuclear factor-κ ligand (RANKL) has a critical role in the etiology of malignancy skeletal complications. The
fully humanized anti-RANKL antibody (denosumab) would seem to be even more effective than bisphosphonates to suppress
bone resorption, as shown in preliminary results .
