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Osteoporosis International
Published in: Osteoporosis International 3/2015

01-03-2015 | Original Article

Changes in skeletal collagen cross-links and matrix hydration in high- and low-turnover chronic kidney disease

Authors: M. R. Allen, C. L. Newman, N. Chen, M. Granke, J. S. Nyman, S. M. Moe

Published in: Osteoporosis International | Issue 3/2015

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Abstract

Summary

Chronic kidney disease (CKD) increases fracture risk. The results of this work point to changes in bone collagen and bone hydration as playing a role in bone fragility associated with CKD.

Introduction

Clinical data have documented a clear increase in fracture risk associated with chronic kidney disease (CKD). Preclinical studies have shown reductions in bone mechanical properties although the tissue-level mechanisms for these differences remain unclear. The goal of this study was to assess collagen cross-links and matrix hydration, two variables known to affect mechanical properties, in animals with either high- or low-turnover CKD.

Methods

At 35 weeks of age (>75 % reduction in kidney function), the femoral diaphysis of male Cy/+ rats with high or low bone turnover rates, along with normal littermate (NL) controls, were assessed for collagen cross-links (pyridinoline (Pyd), deoxypyridinoline (Dpd), and pentosidine (PE)) using a high-performance liquid chromatography (HPLC) assay as well as pore and bound water per volume (pw and bw) using a 1H nuclear magnetic resonance (NMR) technique. Material-level biomechanical properties were calculated based on previously published whole bone mechanical tests.

Results

Cortical bone from animals with high-turnover disease had lower Pyd and Dpd cross-link levels (−21 % each), lower bw (−10 %), higher PE (+71 %), and higher pw (+46 %) compared to NL. Animals with low turnover had higher Dpd, PE (+71 %), and bw (+7 %) along with lower pw (−60 %) compared to NL. Both high- and low-turnover animals had reduced material-level bone toughness compared to NL animals as determined by three-point bending.

Conclusions

These data document an increase in skeletal PE with advanced CKD that is independent of bone turnover rate and inversely related to decline in kidney function. Although hydration changes occur in both high- and low-turnover disease, the data suggest that nonenzymatic collagen cross-links may be a key factor in compromised mechanical properties of CKD.
Literature
1.
Moe S, Drüeke T, Cunningham J, et al. (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). In: Kidney Int. pp 1945–1953
2.
Nickolas TL, McMahon DJ, Shane E (2006) Relationship between moderate to severe kidney disease and hip fracture in the United States. J Am Soc Nephrol 17:3223–3232CrossRefPubMed
3.
Ensrud KE, Lui L-Y, Taylor BC et al (2007) Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med 167:133–139CrossRefPubMed
4.
Anderson S, Halter JB, Hazzard WR et al (2009) Prediction, progression, and outcomes of chronic kidney disease in older adults. J Am Soc Nephrol 20:1199–1209CrossRefPubMed
5.
Jamal SA, West SL, Miller PD (2011) Fracture risk assessment in patients with chronic kidney disease. Osteoporos Int 23:1191–1198CrossRefPubMed
6.
Nitsch D, Mylne A, Roderick PJ et al (2009) Chronic kidney disease and hip fracture-related mortality in older people in the UK. Nephrol Dial Transplant 24:1539–1544CrossRefPubMed
7.
Fusaro M, Gallieni M, Jamal SA (2013) Fractures in chronic kidney disease: neglected, common, and associated with sickness and death. 85:20–22
8.
Negrea LA (2012) Biochemical abnormalities in chronic kidney disease–mineral bone disease. Clinic Rev Bone Miner Metab 10:149–162CrossRef
9.
Kiattisunthorn K, Moe SM (2011) Chronic kidney disease-mineral bone disorder: definitions and rationale for a systemic disorder. Clinic Rev Bone Miner Metab 10:119–127CrossRef
10.
11.
Terpstra AM, Kalkwarf HJ, Shults J et al (2012) Bone density and cortical structure after pediatric renal transplantation. J Am Soc Nephrol 23:715–726CrossRefPubMedCentralPubMed
12.
13.
Miller MA, Chin J, Miller SC, Fox J (1998) Disparate effects of mild, moderate, and severe secondary hyperparathyroidism on cancellous and cortical bone in rats with chronic renal insufficiency. Bone 23:257–266CrossRefPubMed
14.
Moe SM, Chen NX, Newman CL et al (2014) A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD. J Bone Miner Res 29:902–910CrossRefPubMed
15.
Allen MR, Chen NX, Gattone VH et al (2012) Skeletal effects of zoledronic acid in an animal model of chronic kidney disease. Osteoporos Int 24:1471–1481CrossRefPubMedCentralPubMed
16.
Newman CL, Moe SM, Chen NX et al (2014) Cortical bone mechanical properties are altered in an animal model of progressive chronic kidney disease. PLoS One 9:e99262CrossRefPubMedCentralPubMed
17.
Iwamoto J, Seki A, Sato Y, Matsumoto H (2011) Vitamin K2 improves renal function and increases femoral bone strength in rats with renal insufficiency. Calcif Tissue Int 90:50–59CrossRefPubMed
18.
Moe SM, Radcliffe JS, White KE et al (2011) The pathophysiology of early-stage chronic kidney disease-mineral bone disorder (CKD-MBD) and response to phosphate binders in the rat. J Bone Miner Res 26:2672–2681CrossRefPubMed
19.
Seeman E (2006) Bone quality–the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261CrossRefPubMed
20.
Malluche HH, Porter DS, Monier-Faugere MC et al (2012) Differences in bone quality in low- and high-turnover renal osteodystrophy. J Am Soc Nephrol 23:525–532CrossRefPubMedCentralPubMed
21.
22.
Viguet-Carrin S, Garnero P, Delmas PD (2005) The role of collagen in bone strength. Osteoporos Int 17:319–336CrossRefPubMed
23.
Vashishth D, Gibson GJ, Khoury JI et al (2001) Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 28:195–201CrossRefPubMed
24.
Wang X, Bank RA, TeKoppele JM, Agrawal CM (2001) The role of collagen in determining bone mechanical properties. J Orthop Res 19:1021–1026CrossRefPubMed
25.
Currey JD (2003) Role of collagen and other organics in the mechanical properties of bone. Osteoporos Int 14(Suppl 5):S29–S36
26.
Oxlund H, Barckman M, Ørtoft G, Andreassen TT (1995) Reduced concentrations of collagen cross-links are associated with reduced strength of bone. Bone 17:S365–S371
27.
Mitome J, Yamamoto H, Saito M et al (2011) Nonenzymatic cross-linking pentosidine increase in bone collagen and are associated with disorders of bone mineralization in dialysis patients. Calcif Tissue Int 88:521–529CrossRefPubMed
28.
Aoki C, Uto K, Honda K, et al. (2013) Advanced glycation end products suppress lysyl oxidase and induce bone collagen degradation in a rat model of renal osteodystrophy. 93:1170–1183
29.
Iwasaki Y, Kazama JJ, Yamato H, Fukagawa M (2011) Changes in chemical composition of cortical bone associated with bone fragility in rat model with chronic kidney disease. Bone 48:1260–1267CrossRefPubMed
30.
31.
32.
Nyman JS, Gorochow LE, Adam Horch R et al (2013) Partial removal of pore and loosely bound water by low-energy drying decreases cortical bone toughness in young and old donors. J Mech Behav Biomed Mater 22:136–145CrossRefPubMedCentralPubMed
33.
Techawiboonwong A, Song HK, Leonard MB, Wehrli FW (2008) Cortical bone water: in vivo quantification with ultrashort echo-time MR imaging. Radiology 248:824–833CrossRefPubMedCentralPubMed
34.
Gallant MA, Brown DM, Hammond M et al (2014) Bone cell-independent benefits of raloxifene on the skeleton: a novel mechanism for improving bone material properties. Bone 61:191–200CrossRefPubMed
35.
Anumula S, Wehrli SL, Magland J et al (2010) Ultra-short echo-time MRI detects changes in bone mineralization and water content in OVX rat bone in response to alendronate treatment. Bone 46:1391–1399CrossRefPubMedCentralPubMed
36.
37.
Cowley BD, Grantham JJ, Muessel MJ et al (1996) Modification of disease progression in rats with inherited polycystic kidney disease. YAJKD 27:865–879CrossRef
38.
Cowley BD, Gudapaty S, Kraybill AL et al (1993) Autosomal-dominant polycystic kidney disease in the rat. Kidney Int 43:522–534CrossRefPubMed
39.
Horch RA, Wilkens K, Gochberg DF, Does MD (2010) RF coil considerations for short-T2 MRI. Magnetic Resonance Medicine 64:1652–1657CrossRef
40.
Horch RA, Nyman JS, Gochberg DF et al (2010) Characterization of 1H NMR signal in human cortical bone for magnetic resonance imaging. Magnetic Resonance Medicine 64:680–687CrossRef
41.
Horch RA, Gochberg DF, Nyman JS et al (2011) Non-invasive predictors of human cortical bone mechanical properties: T(2)-discriminated H NMR compared with high resolution X-ray. PLoS One 6:e16359CrossRefPubMedCentralPubMed
42.
43.
Manhard MK, Horch RA, Harkins KD et al (2014) Validation of quantitative bound- and pore-water imaging in cortical bone. Magn Reson Med 71:2166–2171CrossRefPubMed
44.
Di Donato A, Ghiggeri GM, Di Duca M et al (1997) Lysyl oxidase expression and collagen cross-linking during chronic adriamycin nephropathy. Nephron 76:192–200CrossRefPubMed
45.
Ureña P, Ferreira A, Kung VT et al (1995) Serum pyridinoline as a specific marker of collagen breakdown and bone metabolism in hemodialysis patients. J Bone Miner Res 10:932–939CrossRefPubMed
46.
Suliman ME, Heimbürger O, Bárány P et al (2003) Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy. J Am Soc Nephrol 14:1614–1622CrossRefPubMed
47.
Mallipattu SK, Uribarri J (2014) Advanced glycation end product accumulation. Curr Opin Nephrol Hypertens 6:547–554CrossRef
48.
Miyata T, Ueda Y, Horie K et al (1998) Renal catabolism of advanced glycation end products: the fate of pentosidine. Kidney Int 53:416–422CrossRefPubMed
49.
Tang SY, Allen MR, Phipps R et al (2009) Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int 20:887–894CrossRefPubMedCentralPubMed
50.
Burr D (2011) Why bones bend but don’t break. 11: 270–285
51.
Bae WC, Chen PC, Chung CB et al (2012) Quantitative ultrashort echo time (UTE) MRI of human cortical bone: correlation with porosity and biomechanical properties. J Bone Miner Res 27:848–857CrossRefPubMedCentralPubMed
Metadata
Title
Changes in skeletal collagen cross-links and matrix hydration in high- and low-turnover chronic kidney disease
Authors
M. R. Allen
C. L. Newman
N. Chen
M. Granke
J. S. Nyman
S. M. Moe
Publication date
01-03-2015
Publisher
Springer London
Published in
Osteoporosis International / Issue 3/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-014-2978-9

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