Nakagawa Kumiko, Pérez Eduardo C, Oh Jun, Santos Fernando, Geldyyev Aman, Gross Marie-L, Schaefer Franz, Schmitt Claus P
Division of Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany.
Nephrol Dial Transplant. 2008 Sep;23(9):2761-7. doi: 10.1093/ndt/gfn143. Epub 2008 Apr 11.
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.
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].
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).
CIN treatment does not impact on growth plate chondrocyte function in uraemic rats, but improves food efficiency and body weight gain.
