Format

Send to

Choose Destination
PLoS One. 2016 Sep 22;11(9):e0163022. doi: 10.1371/journal.pone.0163022. eCollection 2016.

Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency.

Author information

1
Department of Hand and Microsurgery, Tampere University Hospital, Tampere, Finland.
2
Center for Hip Health and Mobility, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.
3
Medical School, University of Tampere, Tampere, Finland.
4
Bone Research Group, UKK-Institute, Tampere, Finland.
5
Department of Laboratory Medicine, Seinäjoki Central Hospital Laboratory, Seinäjoki, Finland.
6
Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, United States of America.
7
Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland.

Abstract

INTRODUCTION:

Phosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI.

METHODS:

Forty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography).

RESULTS:

Sevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p<0.05 for all versus Sham), while sevelamer increased bone mineral density (+2%) and prevented the deleterious changes in bone. In the femoral neck, CRI reduced bone mineral density (-11%) and breaking load (-10%), while sevelamer prevented the decrease in bone mineral density (+6%) so that breaking load did not differ from controls.

CONCLUSIONS:

In this model of stage 3-4 CRI, sevelamer-HCl treatment ameliorated the decreases in femoral midshaft and neck mineral density, and restored bone strength despite prevailing acidosis. Therefore, treatment with sevelamer can efficiently preserve mechanical competence of bone in CRI.

Conflict of interest statement

The authors have declared that no competing interests exist.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center