title: Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Hand and Microsurgery, Tampere University Hospital, Tampere, Finland.|Center for Hip Health and Mobility, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Jokihaara
authors.affiliation: Medical School, University of Tampere, Tampere, Finland.
authors.forename: Ilkka H
authors.initials: IH
authors.lastname: Pörsti
authors.affiliation: Bone Research Group, UKK-Institute, Tampere, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Sievänen
authors.affiliation: Medical School, University of Tampere, Tampere, Finland.
authors.forename: Peeter
authors.initials: P
authors.lastname: Kööbi
authors.affiliation: Bone Research Group, UKK-Institute, Tampere, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Kannus
authors.affiliation: Medical School, University of Tampere, Tampere, Finland.|Department of Laboratory Medicine, Seinäjoki Central Hospital Laboratory, Seinäjoki, Finland.
authors.forename: Onni
authors.initials: O
authors.lastname: Niemelä
authors.affiliation: Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, United States of America.
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
authors.affiliation: Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, United States of America.
authors.forename: Urszula T
authors.initials: UT
authors.lastname: Iwaniec
authors.affiliation: Center for Hip Health and Mobility, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.|Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland.
authors.forename: Teppo L N
authors.initials: TL
authors.lastname: Järvinen