Reduction of whole PTH/intact PTH ratio as a predictor of bone metabolism in cinacalcet treatment of hemodialysis patients with secondary hyperparathyroidism.
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.
Kurajoh
M
M
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.
Inaba
M
M
Okuno
S
S
Nagayama
H
H
Yamada
S
S
Imanishi
Y
Y
Ishimura
E
E
Shoji
S
S
Yamakawa
T
T
Nishizawa
Y
Y
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
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
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