title: Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1-34 versus calcitriol and calcium.
abstract: BACKGROUND
  Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. This is the first randomized controlled study in children comparing treatment with synthetic human PTH 1-34 and calcitriol.
  
  
  OBJECTIVE
  The primary objective was to assess the efficacy and safety of long-term PTH 1-34 vs. calcitriol treatment in the maintenance of normal serum calcium values and renal calcium excretion in children with hypoparathyroidism.
  
  
  METHODS
  The study was conducted at a clinical research center.
  
  
  METHODS
  Subjects included 12 children aged 5-14 yr with chronic hypoparathyroidism and without severe renal or hepatic insufficiency.
  
  
  METHODS
  The study was a 3-yr randomized parallel trial comparing twice-daily calcitriol (plus calcium and cholecalciferol in four daily doses) vs. s.c. PTH 1-34 treatment, with weekly or biweekly monitoring of serum and urine calcium.
  
  
  RESULTS
  Mean predose serum calcium levels were maintained at, or just below, the normal range, and urine calcium levels remained in the normal range throughout the 3-yr study, with no significant differences between treatment groups. Creatinine clearance, corrected for body surface area, did not differ between groups and remained normal throughout the study. Markers of bone turnover were mildly elevated during PTH 1-34 therapy and remained within the normal range during calcitriol therapy. Mean bone mineral density Z-scores at the anterior-posterior lumbar spine, femoral neck, distal radius, and whole body remained within the normal range and did not differ between groups throughout the study. Similarly, height and weight percentiles did not differ between treatment groups and remained normal throughout the 3-yr follow-up.
  
  
  CONCLUSIONS
  We conclude that PTH 1-34 therapy is safe and effective in maintaining stable calcium homeostasis in children with hypoparathyroidism. Additionally, PTH 1-34 treatment allowed normal skeletal development because there were no differences in bone mineral accrual, linear growth, or weight gain between the two treatment arms over the 3-yr study period.
authors.affiliation: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-7510, USA. winer@mail.nih.gov
authors.forename: Karen K
authors.initials: KK
authors.lastname: Winer
authors.forename: Ninet
authors.initials: N
authors.lastname: Sinaii
authors.forename: James
authors.initials: J
authors.lastname: Reynolds
authors.forename: Donna
authors.initials: D
authors.lastname: Peterson
authors.forename: Karen
authors.initials: K
authors.lastname: Dowdy
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Cutler
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000009:adverse effects / Q000627:therapeutic use*; D002118:Calcium / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006128:Growth / Q000187:drug effects; D020249:Hormone Replacement Therapy; D006801:Humans; D007011:Hypoparathyroidism / Q000188:drug therapy*; D007677:Kidney Function Tests; D008134:Long-Term Care; D008274:Magnesium / Q000097:blood; D008297:Male; D010281:Parathyroid Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002120:Calcium Channel Agonists; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium
references.citation: N Engl J Med. 2001 May 10;344(19):1434-41
references.pmid: 11346808
references.citation: Child Nephrol Urol. 1988-1989;9(5):273-6
references.pmid: 2856045
references.citation: Vital Health Stat 11. 2002 May;(246):1-190
references.pmid: 12043359
references.citation: Toxicol Pathol. 2002 May-Jun;30(3):312-21
references.pmid: 12051548
references.citation: Am J Dis Child. 1986 Feb;140(2):139-42
references.pmid: 3753816
references.citation: Hum Mol Genet. 1996 May;5(5):601-6
references.pmid: 8733126
references.citation: J Clin Invest. 1981 Nov;68(5):1261-71
references.pmid: 7298851
references.citation: J Clin Endocrinol Metab. 1998 Oct;83(10):3480-6
references.pmid: 9768650
references.citation: JAMA. 1996 Aug 28;276(8):631-6
references.pmid: 8773636
references.citation: Monatsschr Kinderheilkd. 1990 Mar;138(3):141-6
references.pmid: 2162006
references.citation: J Clin Endocrinol Metab. 2007 Jun;92(6):2087-99
references.pmid: 17311856
references.citation: J Clin Endocrinol Metab. 2003 Sep;88(9):4214-20
references.pmid: 12970289
references.citation: J Clin Endocrinol Metab. 2008 Sep;93(9):3389-95
references.pmid: 18492754
references.citation: N Engl J Med. 1994 Dec 15;331(24):1618-23
references.pmid: 7969342
references.citation: J Bone Miner Res. 1986 Aug;1(4):377-81
references.pmid: 3503551