Background: Increased bone loss has been associated with the development of vascular calcification in patients with chronic renal failure (CRF). In this study, the effect of impaired bone metabolism on aortic calcifications was investigated in uremic rats with or without ovariectomy. Methods: CRF was induced by administration of a 0.75% adenine/2.5% protein diet for 4 weeks. In one group, osteoporosis was induced by ovariectomy (CRF-OVX), while the other group underwent a sham-operation instead (CRF). A third group consisted of ovariectomized rats with normal renal function (OVX). At regular time intervals throughout the study, bone status and aortic calcifications were evaluated by in vivo micro-CT. At sacrifice after 6 weeks of CRF, bone histomorphometry was performed and vascular calcification was assessed by bulk calcium analysis and Von Kossa staining. Results: Renal function was significantly impaired in the CRF-OVX and CRF groups. Trabecular bone loss was seen in all groups. In the CRF-OVX and CRF groups, trabecular bone density was restored after adenine withdrawal, which coincided with cortical bone loss and the development of medial calcifications in the aorta. No significant differences with regard to the degree of aortic calcifications were seen between the two CRF groups. Neither cortical bone loss nor calcifications were seen in the OVX group. Cortical bone loss significantly correlated with the severity of vascular calcification in the CRF-OVX and CRF groups, but no associations with trabecular bone changes were found. Conclusions: Cortical rather than trabecular bone loss is associated with the process of calcification in rats with adenine- induced CRF.

1.
Persy V, D’Haese P: Vascular calcification and bone disease: the calcification paradox. Trends Mol Med 2009;15:405–416.
2.
Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME: Medial localization of mineralization-regulating proteins in association with Monckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 1999;100:2168–2176.
3.
Neven E, Persy V, Dauwe S, De Schutter T, De Broe ME, D’Haese P: Chondrocyte rather than osteoblast conversion of vascular cells underlies medial calcification in uremic rats. Arterioscler Thromb Vasc Biol 2010;30:1740–1750.
4.
Barreto FC, Barreto DV, Moyses RM, Neves CL, Jorgetti V, Draibe SA, Canziani ME, Carvalho AB: Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem. Kidney Int 2006;69:1852–1857.
5.
Nickolas TL, Leonard MB, Shane E: Chronic kidney disease and bone fracture: a growing concern. Kidney Int 2008;74:721–731.
6.
Cunningham J, Sprague SM, Cannata-Andia J, Coco M, Cohen-Solal M, Fitzpatrick L, Goltzmann D, Lafage-Proust MH, Leonard M, Ott S, Rodriguez M, Stehman-Breen C, Stern P, Weisinger J: Osteoporosis in chronic kidney disease. Am J Kidney Dis 2004;43:566–571.
7.
Gal-Moscovici A, Sprague SM: Osteoporosis and chronic kidney disease. Semin Dial 2007;20:423–430.
8.
London GM, Marty C, Marchais SJ, Guerin AP, Metivier F, de Vernejoul MC: Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol 2004;15:1943–1951.
9.
Raggi P, Bellasi A, Ferramosca E, Block GA, Muntner P: Pulse wave velocity is inversely related to vertebral bone density in hemodialysis patients. Hypertension 2007;49:1278–1284.
10.
Guerin AP, London GM, Marchais SJ, Metivier F: Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000;15:1014–1021.
11.
Naves M, Rodriguez-Garcia M, Diaz-Lopez JB, Gomez-Alonso C, Cannata-Andia JB: Progression of vascular calcifications is associated with greater bone loss and increased bone fractures. Osteoporos Int 2008;19:1161–1166.
12.
van Diepen S, Majumdar SR, Bakal JA, McAlister FA, Ezekowitz JA: Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16,294 Patients. Circulation 2008;118:1946–1952.
13.
Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW: Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 2001;68:271–276.
14.
Tanko LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA, Cummings SR: Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Miner Res 2005;20:1912–1920.
15.
Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC: Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 2000;20:1926–1931.
16.
Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V: Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 2004;89:4246–4253.
17.
Price PA, Roublick AM, Williamson MK: Artery calcification in uremic rats is increased by a low protein diet and prevented by treatment with ibandronate. Kidney Int 2006;70:1577–1583.
18.
Persy V, Postnov A, Neven E, Dams G, De Broe M, D’Haese P, De Clerck N: High-resolution X-ray microtomography is a sensitive method to detect vascular calcification in living rats with chronic renal failure. Arterioscler Thromb Vasc Biol 2006;26:2110–2116.
19.
Rodriguez-Garcia M, Gomez-Alonso C, Naves-Diaz M, Diaz-Lopez JB, Diaz-Corte C, Cannata-Andia JB: Vascular calcifications, vertebral fractures and mortality in haemodialysis patients. Nephrol Dial Transplant 2008;24:239–246.
20.
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342:1478–1483.
21.
Nazarian A, Cory E, Muller R, Snyder BD: Shortcomings of DXA to assess changes in bone tissue density and microstructure induced by metabolic bone diseases in rat models. Osteoporos Int 2009;20:123–132.
22.
Negri AL, Barone R, Lombas C, Bogado CE, Zanchetta JR: Evaluation of cortical bone by peripheral quantitative computed tomography in continuous ambulatory peritoneal dialysis patients. Hemodial Int 2006;10:351–355.
23.
Neven E, Dams G, Postnov A, Chen B, De Clerck N, De Broe ME, D’Haese PC, Persy V: Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats. Nephrol Dial Transplant 2009;24:1790–1799.
24.
Ogirima T, Tano K, Kanehara M, Gao M, Wang X, Guo Y, Zhang Y, Guo L, Ishida T: Sex difference of adenine effects in rats: renal function, bone mineral density and sex steroidogenesis. Endocr J 2006;53:407–413.
25.
Park JH, Omi N, Nosaka T, Kitajima A, Ezawa I: Estrogen deficiency and low-calcium diet increased bone loss and urinary calcium excretion but did not alter arterial stiffness in young female rats. J Bone Miner Metab 2008;26:218–225.
26.
Fitzpatrick LA, Turner RT, Ritman ER: Endochondral bone formation in the heart: a possible mechanism of coronary calcification. Endocrinology 2003;144:2214–2219.
27.
Schober HC, Han ZH, Foldes AJ, Shih MS, Rao DS, Balena R, Parfitt AM: Mineralized bone loss at different sites in dialysis patients: implications for prevention. J Am Soc Nephrol 1998;9:1225–1233.
28.
Parfitt AM: A structural approach to renal bone disease. J Bone Miner Res 1998;13:1213–1220.
29.
Shanahan CM: Mechanisms of vascular calcification in renal disease. Clin Nephrol 2005;63:146–157.
30.
Cozzolino M, Ketteler M: The link between bone and cardiovascular disease in CKD: new insights into pathogenesis and treatment. Int J Artif Organs 2009;32:65–66.
31.
Giachelli CM: Vascular calcification: in vitro evidence for the role of inorganic phosphate. J Am Soc Nephrol 2003;14:S300–S304.
32.
Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000;87:E10–E17.
33.
Yang H, Curinga G, Giachelli CM: Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int 2004;66:2293–2299.
34.
Pasch A, Schaffner T, Huynh-Do U, Frey BM, Frey FJ, Farese S: Sodium thiosulfate prevents vascular calcifications in uremic rats. Kidney Int 2008;74:1444–1453.
35.
Tamagaki K, Yuan Q, Ohkawa H, Imazeki I, Moriguchi Y, Imai N, Sasaki S, Takeda K, Fukagawa M: Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia. Nephrol Dial Transplant 2006;21:651–659.
36.
Roman-Garcia P, Carrillo-Lopez N, Fernandez-Martin JL, Naves-Diaz M, Ruiz-Torres MP, Cannata-Andia JB: High phosphorus diet induces vascular calcification, a related decrease in bone mass and changes in the aortic gene expression. Bone 2009;46:121–128.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.