Cinacalcet does not affect longitudinal growth but increases body weight gain in experimental uraemia.
BACKGROUND
Cinacalcet (CIN) efficiently suppresses parathyroid hormone (PTH) secretion by the activation of the calcium-sensing receptor (CaR). Epiphyseal chondrocytes also express the CaR and its activation promotes cell proliferation and differentiation in vitro. Hence, the impact of CIN on the growth plate function requires assessment before routine administration in children.


METHODS
We treated subtotally nephrectomized (SNX) and sham-operated, ad lib and pair-fed Sprague-Dawley rats with CIN (15 mg/kg day) or solvent (S) for 14 days p.o. and assessed whole body and tibia length gain, growth plate morphology, osseous front advance (OFA) (calcein staining) and chondrocyte proliferation rate [5-bromo-2'-deoxyuridine (BrdU) staining].


RESULTS
Total body length gain did not differ after 7 and 14 days (SNX + CIN 2.9 +/- 0.6, SNX + S 3.0 +/- 0.7; sham + CIN 4.2 +/- 0.4, sham + S 4.5 +/- 0.4; sham pair-fed + CIN 3.3 +/- 0.5, sham pair-fed + S 3.5 +/- 0.6 cm/14 days; P = n.s.). Tibia length, the height of the total growth plate and the hypertrophic zone, OFA and chondrocyte proliferation rate were similar with CIN and S. Serum Ca(2+) declined with CIN treatment; PTH was 61% lower in CIN- compared to S-treated SNX (P < 0.05). Food intake was similar, whereas body weight gain (21.6 +/- 8.7 versus 12.7 +/- 11.2 g) and body weight gain per food intake (141 +/- 50 versus 77 +/- 70 g/kg) improved in CIN- versus S-treated SNX animals (P < 0.05).


CONCLUSIONS
CIN treatment does not impact on growth plate chondrocyte function in uraemic rats, but improves food efficiency and body weight gain.
Nakagawa
Kumiko
K
Division of Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany.
Pérez
Eduardo C
EC
Oh
Jun
J
Santos
Fernando
F
Geldyyev
Aman
A
Gross
Marie-L
ML
Schaefer
Franz
F
Schmitt
Claus P
CP
D000818:Animals; D001699:Biometry; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D000069449:Cinacalcet; D006132:Growth Plate / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000033:anatomy & histology; D014511:Uremia / Q000503:physiopathology*; D015430:Weight Gain / Q000187:drug effects*
D009281:Naphthalenes; D000069449:Cinacalcet