title: Therapy of Hypoparathyroidism With PTH(1-84): A Prospective Six Year Investigation of Efficacy and Safety.
abstract: Human recombinant (rh)PTH(1-84) was recently approved for the treatment of refractory hypoparathyroidism, based upon a short-term phase 3 clinical trial. Long-term data are needed, because no time limit was placed on the treatment period.
  
  
  
  We studied the effect of long-term rhPTH(1-84) treatment in hypoparathyroidism for up to 6 years.
  
  
  
  Prospective open-label study.
  
  
  
  Referral center.
  
  
  
  A total of 33 subjects with hypoparathyroidism.
  
  
  
  rhPTH(1-84) treatment was initiated at a starting dose of 100 μg every other day for 6 years. Due to the availability of new dosages during the 6-year time period of the study, the dose could be and was adjusted for most patients to a daily dosing regimen.
  
  
  
  Supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 mo and then biannually), serum phosphorus, bone turnover markers, and bone mineral density (BMD) biannually.
  
  
  
  Treatment with rhPTH(1-84) progressively reduced supplemental calcium requirements over 6 years by 53% (P < .0001) and 1,25-dihydroxyvitamin D requirements by 67% (P < .0001). Sixteen subjects (48%) were able to eliminate 1,25-dihydroxyvitamin D supplementation completely. Serum calcium concentration remained stable, and urinary calcium excretion fell. Lumbar spine BMD increased (3.8 ± 1%, P = .004) as did total hip BMD (2.4 ± 1%, P = .02), whereas femoral neck BMD remained stable and the distal one third radius decreased (-4.4 ±1%, P < .0001). Bone turnover markers increased significantly, reaching a 3-fold peak above baseline values at 1 year and subsequently declining but remaining higher than pretreatment values. Hypercalcemia was uncommon (12 episodes over 6 y; 2.5% of all values).
  
  
  
  Long-term, continuous therapy of hypoparathyroidism for 6 years with rhPTH(1-84) is associated with reductions in supplemental calcium and calcitriol requirements, stable serum calcium concentration, and reduced urinary calcium excretion. The safety profile remains good. These data represent the longest experience with the therapeutic use of PTH for any condition and demonstrate its long-term efficacy and safety in hypoparathyroidism.
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Mishaela R
authors.initials: MR
authors.lastname: Rubin
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Cusano
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Fan
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Delgado
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Chengchen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Aline G
authors.initials: AG
authors.lastname: Costa
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Dworakowski
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D016723:Bone Remodeling; D002118:Calcium / Q000097:blood / Q000652:urine; D019587:Dietary Supplements; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D014807:Vitamin D; D010758:Phosphorus; C097949:1,25-dihydroxyvitamin D; D002118:Calcium