Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 95, Issue 3, Pages 1279-1287Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2009-0233
Keywords
-
Categories
Funding
- National Institutes of Health [DK 51081, DK 073039, DK071158]
- University of Pittsburgh Clinical Translational Sciences Awards, National Institutes of Health/National Center for Research Resources/Clinical Translational Science [UL1 RR024153, MO-1 RR000056]
Ask authors/readers for more resources
Context: PTH is the only approved skeletal anabolic agent for the treatment of human osteoporosis. Unlike PTH, which is a mixed anabolic and catabolic agent, PTHrP displays features suggesting that it may be a pure anabolic agent when intermittently administered. The full dose range of PTHrP is unknown. Objectives: The primary objective of the study was to define the complete therapeutic window and dose-limiting toxicities of PTHrP. The secondary objective was to determine whether PTHrP retains a pure anabolic profile at the highest usable doses. Design: This was a single-blinded, two-part, dose-escalating clinical trial. Setting: The study was conducted in a university academic setting. Patients or Other Participants: Participants included 41 healthy postmenopausal women between the ages of 45 and 75 yr. Intervention: Interventions included PTHrP(1-36) or placebo in a dose-escalating design for 3 wk. Main Outcome Measures: Safety measures (hypercalcemia, nausea, vomiting, hemodynamics, flushing, miscellaneous) and bone turnover markers were measured. Results: Intermittent PTHrP was administered safely and without serious adverse events in subjects receiving 500 and 625 mu g/d for 3 wk. Subjects receiving 750 mu g/d developed mild hypercalcemia. Bone turnover markers suggested that even at the highest doses, daily sc PTHrP may not activate bone resorption, i.e. may be purely anabolic. Interestingly, when hypercalcemia occurred, it may have resulted not from bone resorption but from activation of intestinal calcium absorption by 1,25 dihydroxyvitamin D. Conclusions: In doses as high as 750 mu g/d, in contrast to PTH, intermittently administered PTHrP appears to act as a pure skeletal anabolic agent. Surprisingly, PTHrP in the high doses studied activates 1,25 dihydroxyvitamin D production. Dosing information obtained herein can be used to design a longer term head-to-head comparative efficacy trial of PTHrP vs. PTH. (J Clin Endocrinol Metab 95: 1279-1287, 2010)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available