title: Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study.
abstract: In hypoparathyroidism, inappropriately low levels of parathyroid hormone lead to unbalanced mineral homeostasis. The objective of this study was to determine the effect of recombinant human parathyroid hormone, rhPTH(1-84), on phosphate and vitamin D metabolite levels in patients with hypoparathyroidism. Following pretreatment optimization of calcium and vitamin D doses, 124 patients in a phase III, 24-week, randomized, double-blind, placebo-controlled study of adults with hypoparathyroidism received subcutaneous injections of placebo or rhPTH(1-84) (50 µg/day, titrated to 75 and then 100 µg/day, to permit reductions in oral calcium and active vitamin D doses while maintaining serum calcium within 2.0-2.2 mmol/L). Predefined endpoints related to phosphate homeostasis and vitamin D metabolism were analyzed. Serum phosphate levels decreased rapidly from the upper normal range and remained lower with rhPTH(1-84) (P < 0.001 vs. placebo). At week 24, serum calcium-phosphate product was lower with rhPTH(1-84) vs. placebo (P < 0.001). rhPTH(1-84) treatment resulted in significant reductions in oral calcium dose compared with placebo (P < 0.001) while maintaining serum calcium. After pretreatment optimization, baseline serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels were within the normal range in both groups. After 24 weeks, 1,25(OH)2D levels were unchanged in both treatment groups, despite significantly greater reductions in active vitamin D dose in the rhPTH(1-84) group. In hypoparathyroidism, rhPTH(1-84) reduces serum phosphate levels, improves calcium-phosphate product, and maintains 1,25(OH)2D and serum calcium in the normal range while allowing significant reductions in active vitamin D and oral calcium doses.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, E18-A, 200 1st Street SW, Rochester, MN, 55905, USA. clarke.bart@mayo.edu.
authors.forename: Bart L
authors.identifier: http://orcid.org/0000-0002-3801-9546
authors.initials: BL
authors.lastname: Clarke
authors.affiliation: Section of Endocrinology, University of Chicago Medicine, 5841 South Maryland Avenue, MC1027, Chicago, IL, 60637, USA.
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Vokes
authors.affiliation: Division of Endocrinology, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, Room 864, New York, NY, 10032, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
authors.affiliation: Endocrine Research Unit, San Francisco Department of Veterans Affairs Medical Center, University of California, 1700 Owens Street, San Francisco, CA, 94158, USA.
authors.forename: Dolores M
authors.initials: DM
authors.lastname: Shoback
authors.affiliation: NPS Pharmaceuticals, Inc., 300 Shire Way, Lexington, MA, 02421, USA.
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Lagast
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, 50 Blossom Street, Thier-1123, Boston, MA, 02114, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mannstadt
mesh_terms: D000328:Adult; D002118:Calcium / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D010710:Phosphates / Q000097:blood*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood*
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D011994:Recombinant Proteins; D014807:Vitamin D; D002118:Calcium
keywords: Hypoparathyroidism; Parathyroid hormone; Phosphate; Vitamin D; rhPTH(1–84)