title: Inhibition of bone resorption by the bisphosphonate BM 21.0955 is not associated with an alteration of the renal handling of calcium in rats infused with parathyroid hormone-related protein.
abstract: Hypercalcaemia of malignancy is determined by an increase of bone resorption and/or renal tubular reabsorption of calcium (Ca). However, this latter component has been found to vary in certain patients during therapy with bone resorption inhibitors such as bisphosphonates. We investigated the possible effects of the highly potent bisphosphonate BM 21.0955 on the renal handling of Ca in thyroparathyroidectomized rats made hypercalcaemic by the stimulation of both bone resorption and renal tubular reabsorption of Ca induced by the chronic infusion of parathyroid hormone-related protein (PTHrP). Dose-dependent inhibition of bone resorption by BM 21.0955, as indicated by the decrease in fasting urinary Ca excretion from 64.0 +/- 7.3 to 6.7 +/- 3.1 nmol/ml GFR, was associated with a change in plasma Ca from 2.97 +/- 0.10 to 2.63 +/- 0.16 mmol/l. However, the relationship between urinary Ca excretion and plasma Ca was not altered, either at endogenous plasma Ca concentration or during the acute infusion of Ca. Similarly, an index of renal tubular reabsorption of Ca calculated from the slope of the linear portion of the relationship between urinary Ca and plasma Ca, which was increased by PTHrP administration, was not influenced by BM 21.0955 therapy (2.59 +/- 0.15 vs. 2.55 +/- 0.11 mmol/l GFR). These results indicate that BM 21.0955, which is one of the most potent bisphosphonates inhibiting bone resorption, did not affect the renal tubular reabsorption of Ca enhanced by PTHrP.
authors.affiliation: Division of Clinical Pathophysiology, University Hospital, Geneva, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Rizzoli
authors.forename: J
authors.initials: J
authors.lastname: Caverzasio
authors.forename: F
authors.initials: F
authors.lastname: Bauss
authors.forename: J P
authors.initials: JP
authors.lastname: Bonjour
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism*; D004164:Diphosphonates / Q000494:pharmacology*; D000077557:Ibandronic Acid; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004164:Diphosphonates; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D002118:Calcium; D000077557:Ibandronic Acid