title: Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism.
abstract: BACKGROUND
  Vitamin D therapy for hypoparathyroidism does not restore PTH-dependent renal calcium reabsorption, which can lead to renal damage. An alternative approach, PTH 1-34 administered twice daily, provides acceptable long-term treatment but is associated with nonphysiological serum calcium fluctuation.
  
  
  OBJECTIVE
  Our objective was to compare continuous PTH 1-34 delivery, by insulin pump, with twice-daily delivery.
  
  
  METHODS
  In a 6-month, open-label, randomized, crossover trial, PTH 1-34 was delivered by pump or twice-daily sc injection. After each 3-month study period, serum and 24-h urine mineral levels and bone turnover markers were measured daily for 3 d, and 24-h biochemical profiles were determined for serum minerals and 1,25-dihydroxyvitamin D(3) and for urine minerals and cAMP. STUDY PARTICIPANTS AND SETTING: Eight patients with postsurgical hypoparathyroidism (mean ± sd age 46 ± 5.6 yr) participated at a tertiary care referral center.
  
  
  RESULTS
  Pump vs. twice-daily delivery of PTH 1-34 produced less fluctuation in serum calcium, a more than 50% reduction in urine calcium (P = 0.002), and a 65% reduction in the PTH dose to maintain eucalcemia (P < 0.001). Pump delivery also produced higher serum magnesium level (P = 0.02), normal urine magnesium, and reduced need for magnesium supplements. Finally, pump delivery normalized bone turnover markers and significantly lowered urinary cross-linked N-telopeptide of type 1 collagen and pyridinium crosslinks compared with twice-daily injections (P < 0.05).
  
  
  CONCLUSIONS
  Pump delivery of PTH 1-34 provides the closest approach to date to physiological replacement therapy for hypoparathyroidism.
authors.affiliation: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892-7510, USA. winerk@mail.nih.gov
authors.forename: Karen K
authors.initials: KK
authors.lastname: Winer
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Shrader
authors.forename: Donna
authors.initials: D
authors.lastname: Peterson
authors.forename: Michaele
authors.initials: M
authors.lastname: Smith
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Cutler
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D007332:Insulin Infusion Systems; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000138:chemical synthesis; D010758:Phosphorus / Q000097:blood; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy; D014807:Vitamin D / Q000097:blood
chemical_list: D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D008274:Magnesium
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