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Accumulated uremic toxins attenuate bone mechanical properties in rats with chronic kidney disease.

Abstract

The prevalence of hip fracture is very high among patients with chronic kidney disease (CKD); however, the reason for this is unclear. We examined the effects of accumulated uremic toxins on bone chemical composition and elastic mechanical properties. Rats underwent thyroparathyroidectomy and progressive partial nephrectomy (TPTx-Nx), and were administered with vehicle or AST-120 to reduce serum indoxyl sulfate (IS) levels. Bone mechanical properties, bone mineral density (BMD), cortical bone chemical composition, and histomorphometry were determined. Storage modulus was reduced in TPTx-Nx rats compared with rats that underwent TPTx alone. BMD and histomorphometric parameters did not differ between the groups. In terms of cortical bone chemical composition, the mineral/matrix ratio and carbonate substitution was increased, whereas crystallinity was decreased in TPTx-Nx rats. The enzymatic crosslink ratio and pentosidine:matrix ratio were increased in TPTx-Nx rats. AST-120 abolished the effects of TPTx-Nx and decreased the serum IS concentration. Stepwise multiple regression analysis revealed that the pentosidine:matrix and mineral:matrix ratios were independent contributors to the storage modulus. In conclusion, the accumulated uremic toxins, including IS, seem to play an important role in deteriorating bone mechanical properties by altering the chemical composition of bone. This mechanism may account for the increased prevalence of hip fracture among patients with CKD.

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  • Authors+Show Affiliations

    ,

    Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201, Japan.

    , , ,

    Source

    Bone 57:2 2013 Dec pg 477-83

    MeSH

    Animals
    Biomechanical Phenomena
    Bone Density
    Bone and Bones
    Creatinine
    Elastic Modulus
    Femur
    Kidney Function Tests
    Linear Models
    Male
    Rats
    Rats, Sprague-Dawley
    Renal Insufficiency, Chronic
    Spectrum Analysis, Raman
    Uremia

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23920356

    Citation

    Iwasaki, Yoshiko, et al. "Accumulated Uremic Toxins Attenuate Bone Mechanical Properties in Rats With Chronic Kidney Disease." Bone, vol. 57, no. 2, 2013, pp. 477-83.
    Iwasaki Y, Kazama JJ, Yamato H, et al. Accumulated uremic toxins attenuate bone mechanical properties in rats with chronic kidney disease. Bone. 2013;57(2):477-83.
    Iwasaki, Y., Kazama, J. J., Yamato, H., Shimoda, H., & Fukagawa, M. (2013). Accumulated uremic toxins attenuate bone mechanical properties in rats with chronic kidney disease. Bone, 57(2), pp. 477-83. doi:10.1016/j.bone.2013.07.037.
    Iwasaki Y, et al. Accumulated Uremic Toxins Attenuate Bone Mechanical Properties in Rats With Chronic Kidney Disease. Bone. 2013;57(2):477-83. PubMed PMID: 23920356.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Accumulated uremic toxins attenuate bone mechanical properties in rats with chronic kidney disease. AU - Iwasaki,Yoshiko, AU - Kazama,Junichiro James, AU - Yamato,Hideyuki, AU - Shimoda,Hiroshi, AU - Fukagawa,Masafumi, Y1 - 2013/08/03/ PY - 2013/04/30/received PY - 2013/07/22/revised PY - 2013/07/25/accepted PY - 2013/8/8/entrez PY - 2013/8/8/pubmed PY - 2014/6/12/medline KW - AST-120 KW - Chronic kidney disease KW - Storage module KW - Uremic toxins SP - 477 EP - 83 JF - Bone JO - Bone VL - 57 IS - 2 N2 - The prevalence of hip fracture is very high among patients with chronic kidney disease (CKD); however, the reason for this is unclear. We examined the effects of accumulated uremic toxins on bone chemical composition and elastic mechanical properties. Rats underwent thyroparathyroidectomy and progressive partial nephrectomy (TPTx-Nx), and were administered with vehicle or AST-120 to reduce serum indoxyl sulfate (IS) levels. Bone mechanical properties, bone mineral density (BMD), cortical bone chemical composition, and histomorphometry were determined. Storage modulus was reduced in TPTx-Nx rats compared with rats that underwent TPTx alone. BMD and histomorphometric parameters did not differ between the groups. In terms of cortical bone chemical composition, the mineral/matrix ratio and carbonate substitution was increased, whereas crystallinity was decreased in TPTx-Nx rats. The enzymatic crosslink ratio and pentosidine:matrix ratio were increased in TPTx-Nx rats. AST-120 abolished the effects of TPTx-Nx and decreased the serum IS concentration. Stepwise multiple regression analysis revealed that the pentosidine:matrix and mineral:matrix ratios were independent contributors to the storage modulus. In conclusion, the accumulated uremic toxins, including IS, seem to play an important role in deteriorating bone mechanical properties by altering the chemical composition of bone. This mechanism may account for the increased prevalence of hip fracture among patients with CKD. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/23920356/Accumulated_uremic_toxins_attenuate_bone_mechanical_properties_in_rats_with_chronic_kidney_disease L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(13)00299-8 DB - PRIME DP - Unbound Medicine ER -