An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism.
OBJECTIVE
Cinacalcet lowers plasma parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism (sHPT), but the bone histologic response has not been described. This prospective, double-blind, placebo-controlled trial assessed the effects of cinacalcet on bone histology and serum markers of bone metabolism in dialysis patients with sHPT.


METHODS
Patients with intact PTH (iPTH) > or = 300 pg/ml were randomly assigned 2:1 to receive cinacalcet or placebo with concurrent vitamin D and/or phosphate binder therapy. Cinacalcet (30 - 180 mg/day) was used to achieve iPTH levels < or = 200 pg/ml. Bone biopsies were performed before and after one year of treatment.


RESULTS
Baseline and end-of-study data were available from 32 patients (19 cinacalcet, 13 placebo). Baseline bone turnover was elevated in 27, reduced in 3 and normal in 2 patients. Serum bone-specific alkaline phosphatase (BSAP) and N-telopeptide (NTx) were elevated. Cinacalcet treatment decreased PTH and diminished activation frequency, bone formation rate/bone surface, and fibrosis surface/bone surface. Adynamic bone was observed in three patients receiving cinacalcet; in two of these, PTH levels were persistently low (< 100 pg/ml). The histomorphometric parameter changes in bone corresponded to PTH, BSAP and NTx reductions. Bone mineralization parameters remained normal.


CONCLUSIONS
Treatment with cinacalcet lowered PTH and reduced bone turnover and tissue fibrosis among most dialysis patients with biochemical evidence of sHPT.
Malluche
H H
HH
University of Kentucky, Division of Nephrology, Bone and Mineral Metabolism, Lexington, KY 40536-0084, USA. hhmall@uky.edu
Monier-Faugere
M-C
MC
Wang
G
G
Frazã O
J M
JM
Charytan
C
C
Coburn
J W
JW
Coyne
D W
DW
Kaplan
M R
MR
Baker
N
N
McCary
L C
LC
Turner
S A
SA
Goodman
W G
WG
D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D000069449:Cinacalcet; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications / Q000188:drug therapy*; D007085:Ilium / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D011446:Prospective Studies; D006435:Renal Dialysis
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D009281:Naphthalenes; D000069449:Cinacalcet