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Characterization of the effect of chronic administration of a calcium-sensing receptor antagonist, ronacaleret, on renal calcium excretion and serum calcium in postmenopausal women.

Abstract：

:Ronacaleret is an orally-active calcium-sensing receptor (CaSR) antagonist that has the potential for therapeutic utility in the stimulation of PTH release, notably as a bone anabolic agent comparable to recombinant human PTH(1-34) (rhPTH(1-34)). A recent study has shown that, despite the ability to increase circulating PTH levels in postmenopausal women in a dose-dependent manner, minimal effects of ronacaleret on bone mineral density have been observed. Therefore, the purpose of this study was to characterize the PTH profile as well as calcium metabolism parameters as a marker of PTH biological activity following the administration of ronacaleret or rhPTH(1-34). Administration of ronacaleret led to lower peak levels of PTH than were observed with rhPTH(1-34), however, greater total PTH exposure was observed. Further, chronic administration of either agent was associated with increases in urinary calcium excretion and serum calcium levels, with the magnitude of the changes following ronacaleret significantly greater than that for rhPTH(1-34). The greater magnitude of effects observed with ronacaleret is likely due to the greater total PTH exposure, and is potentially reflective of a state comparable to mild hyperparathyroidism. It is not clear whether the administration of all calcilytics would lead to a similar result, or is due to characteristics specific to ronacaleret.

journal_name

Bone

journal_title

Bone

authors

Caltabiano S,Dollery CT,Hossain M,Kurtinecz MT,Desjardins JP,Favus MJ,Kumar R,Fitzpatrick LA

doi

10.1016/j.bone.2013.05.021

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

154-62

issue

1

eissn

8756-3282

issn

1873-2763

pii

S8756-3282(13)00217-2

journal_volume

56

pub_type

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