title: Management of hypercalcemia in relation to pathophysiology.
abstract: Hypercalcemia results from an imbalance between the fluxes of calcium (Ca) entering and leaving the extracellular space. The two most important influxes are the net intestinal Ca absorption and the net skeletal Ca resorption, whereas the renal excretion represents the main route of elimination. When produced in excess, various factors, particularly calciotropic hormones and cytokines, can disturb the Ca fluxes at intestinal, skeletal and renal tubular sites. If the excessive production of these substances cannot be controlled by surgical or pharmacological means, the next most rational therapeutic strategy should be aimed at correcting those Ca fluxes which are abnormally increased. In hypercalcemia of malignancy (HM), an augmentation in net bone resorption (BR) is observed in most patients. However, a sustained stimulation in tubular Ca reabsorption (TRCa), despite correction of volume depletion by saline infusions, may not only contribute to the hypercalcemia, but in some cases it appears to be the prevailing disturbance. In these patients the effects of the antiresorbing agent clodronate (500 mg/8 h iv in one single infusion) is incomplete, despite the normalisation of BR. Thus, administration of an antiresorbing agent, such as clodronate, is the treatment of choice in HM with elevated BR and normal TRCa. It should be given with other therapeutic agents when a sustained increase in TRCa is the prevailing mechanism for hypercalcemia. In this regard, experimental studies suggest that the agent WR-2721, which specifically inhibits TRCa could be an effective drug for rapidly lowering plasma Ca in HM with high TRCa.
authors.affiliation: Department of Medicine, University Hospital, Geneva, Switzerland.
authors.forename: J P
authors.initials: JP
authors.lastname: Bonjour
authors.forename: R
authors.initials: R
authors.lastname: Rizzoli
authors.forename: S
authors.initials: S
authors.lastname: Hirschel-Scholz
authors.forename: J
authors.initials: J
authors.lastname: Caverzasio
mesh_terms: D004999:Amifostine / Q000627:therapeutic use*; D001862:Bone Resorption / Q000187:drug effects*; D004002:Clodronic Acid / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*
chemical_list: D004164:Diphosphonates; D009946:Organothiophosphorus Compounds; D004002:Clodronic Acid; D004999:Amifostine