Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Apr;87(4):846-56.
doi: 10.1038/ki.2014.349. Epub 2014 Oct 22.

Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism

Geert J Behets  1 , Goce Spasovski  2 , Lulu R Sterling  3 , William G Goodman  3 , David M Spiegel  3 , Marc E De Broe  4 , Patrick C D'Haese  1
Affiliations
Clinical Trial

Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism

Geert J Behets et al. Kidney Int. 2015 Apr.

Abstract

The multicenter, single-arm BONAFIDE study characterized the skeletal response to cinacalcet in adult dialysis patients with plasma parathyroid hormone (PTH) levels of 300 pg/ml or more, serum calcium of 8.4 mg/dl or more, bone-specific alkaline phosphatase over 20.9 ng/ml and biopsy-proven high-turnover bone disease. Of 110 enrolled patients, 77 underwent a second bone biopsy with quantitative histomorphometry after 6-12 months of cinacalcet treatment. The median PTH decreased from 985 pg/ml at baseline to 480 pg/ml at the end of study (weeks 44-52). Bone formation rate/tissue area decreased from 728 to 336 μm(2)/mm(2)/day, osteoblast perimeter/osteoid perimeter decreased from 17.4 to 13.9%, and eroded perimeter/bone perimeter decreased from 12.7 to 8.3%. The number of patients with normal bone histology increased from none at baseline to 20 at 12 months. Two patients had adynamic bone at the end of study with a PTH under 150 pg/ml, and one patient with overt hypophosphatemia at baseline that reoccurred during follow-up developed osteomalacia. Thus, long-term treatment with cinacalcet substantially reduced PTH, diminished the elevated bone formation rate/tissue area, lowered several biochemical markers of high-turnover bone disease toward normal, and generally improved bone histology. Twenty patients had normal bone histology at follow-up, whereas most had mild hyperparathyroidism or mixed uremic osteodystrophy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study design and treatment schema.
Figure 2
Figure 2
Subject disposition by treatment phase.
Figure 3
Figure 3
Comparison of PTH level at baseline and efficacy assessment phase (median-IQR-range). P-value: Wilcoxon-signed rank test.
Figure 4
Figure 4
Primary efficacy end point: comparison of BFR/T.Ar (median-IQR-range) at baseline and end of study. P-value: Wilcoxon signed-rank test. BFR, bone formation rate; T.Ar, tissue area.
Figure 5
Figure 5
Evolution of type of renal osteodystrophy after cinacalcet treatment.
See this image and copyright information in PMC

References

    1. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011;6:913–921. - PubMed
    1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD–MBD Work Group KDIGO Clinical practice guidelines for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease—mineral and bone disorder (CKD-MBD) Kidney Int. 2009;76 (Suppl 113:S1–S130. - PubMed
    1. Quarles LD. Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Exp Cell Res. 2012;318:1040–1048. - PMC - PubMed
    1. Moe SM, Saifullah A, LaClair RE, et al. A randomized trial of cholecalciferol versus doxercalciferol for lowering parathyroid hormone in chronic kidney disease. Clin J Am Soc Nephrol. 2010;5:299–306. - PMC - PubMed
    1. Goodman WG, Hladik GA, Turner SA, et al. The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol. 2002;13:1017–1024. - PubMed

Publication types

MeSH terms

LinkOut - more resources