title: Reduction of whole PTH/intact PTH ratio as a predictor of bone metabolism in cinacalcet treatment of hemodialysis patients with secondary hyperparathyroidism.
abstract: In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker.
  
  
  BACKGROUND
  Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients.
  
  
  METHODS
  Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT.
  
  
  RESULTS
  Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks.
  
  
  CONCLUSIONS
  W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Internal Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kurajoh
authors.forename: M
authors.initials: M
authors.lastname: Inaba
authors.forename: S
authors.initials: S
authors.lastname: Okuno
authors.forename: H
authors.initials: H
authors.lastname: Nagayama
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Imanishi
authors.forename: E
authors.initials: E
authors.lastname: Ishimura
authors.forename: S
authors.initials: S
authors.lastname: Shoji
authors.forename: T
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D016723:Bone Remodeling / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications / Q000188:drug therapy*; D007527:Isoenzymes / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000097:blood* / Q000378:metabolism; D010455:Peptides / Q000097:blood; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis; D000071681:Tartrate-Resistant Acid Phosphatase; D014511:Uremia / Q000150:complications / Q000628:therapy
chemical_list: D024042:Collagen Type I; D007527:Isoenzymes; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D010758:Phosphorus; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium; D000069449:Cinacalcet
references.citation: Osteoporos Int. 2008 May;19(5):709-16
references.pmid: 18239958
references.citation: Nephrol Dial Transplant. 2005 Oct;20(10):2186-93
references.pmid: 16030053
references.citation: Clin J Am Soc Nephrol. 2008 Jan;3(1):36-45
references.pmid: 18178780
references.citation: Clin Endocrinol (Oxf). 2008 Aug;69(2):189-96
references.pmid: 18221403
references.citation: Nephrol Dial Transplant. 2007 Jun;22(6):1645-57
references.pmid: 17307749
references.citation: J Clin Endocrinol Metab. 2005 Oct;90(10):5774-8
references.pmid: 16046589
references.citation: Kidney Int. 1999 Mar;55(3):1019-27
references.pmid: 10027939
references.citation: Calcif Tissue Int. 1998 Aug;63(2):102-6
references.pmid: 9685512
references.citation: Clin Chem. 1997 Nov;43(11):2058-63
references.pmid: 9365389
references.citation: Clin Chem. 1995 Nov;41(11):1560-6
references.pmid: 7586543
references.citation: Clin Lab. 2000;46(5-6):295-9
references.pmid: 10853240
references.citation: J Clin Endocrinol Metab. 2000 Nov;85(11):4157-61
references.pmid: 11095447
references.citation: Kidney Int. 2006 Jul;70(2):345-50
references.pmid: 16788691
references.citation: Kidney Int. 2008 Sep;74(6):775-81
references.pmid: 18528319
references.citation: J Bone Miner Res. 2001 Apr;16(4):605-14
references.pmid: 11315988
references.citation: Metabolism. 1999 Jul;48(7):904-9
references.pmid: 10421234
references.citation: Nephrol Dial Transplant. 2003 Apr;18(4):759-68
references.pmid: 12637646
references.citation: Clin Chim Acta. 2007 Feb;376(1-2):205-12
references.pmid: 17045980
references.citation: Eur J Endocrinol. 2005 Oct;153(4):587-94
references.pmid: 16189180
references.citation: Calcif Tissue Int. 2008 Apr;82(4):278-87
references.pmid: 18421493
references.citation: J Clin Endocrinol Metab. 2005 Jan;90(1):135-41
references.pmid: 15522938
references.citation: Kidney Int. 2005 Sep;68(3):1236-43
references.pmid: 16105056
references.citation: Osteoporos Int. 1999;9(6):525-31
references.pmid: 10624460
references.citation: Clin Chem. 2004 Feb;50(2):385-90
references.pmid: 14684623
references.citation: J Am Soc Nephrol. 2005 Mar;16(3):800-7
references.pmid: 15689407
references.citation: N Engl J Med. 2004 Apr 8;350(15):1516-25
references.pmid: 15071126
references.citation: J Clin Endocrinol Metab. 1999 Nov;84(11):4287-90
references.pmid: 10566687
references.citation: Clin Chem. 1998 Apr;44(4):805-9
references.pmid: 9554492
references.citation: Osteoporos Int. 2005 May;16(5):517-25
references.pmid: 15322741