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Published in: Osteoporosis International 2/2005

01-02-2005 | Original Article

Effective doses of ibandronate do not influence the 3-year progression of aortic calcification in elderly osteoporotic women

Authors: László B. Tankó, Gerong Qin, Peter Alexandersen, Yu Z. Bagger, Claus Christiansen

Published in: Osteoporosis International | Issue 2/2005

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Abstract

Animal experiments revealed conflicting results as to the impact of bisphosphonate treatment on atherosclerosis and related vascular calcification. The effect of long-term treatment with clinical doses of bisphosphonates on aortic calcification (AC) in an “at-risk” population of osteoporotic elderly women has not been assessed systematically. In the present analysis including 474 women (55–80 years) participating in two 3-year randomized, placebo-controlled clinical trials, we assessed the simultaneous impact of ibandronate given either orally (2.5 mg daily or 20 mg intermittently) or intravenously (0.5 mg or 1.0 mg IV every 3 months) on bone mass and AC. All women received calcium and vitamin D supplements. Bone mineral density (BMD) was measured at the lumbar spine and the total hip using dual-energy X-ray absorptiometry (DXA). Calcified deposits of the lumbar aorta (L1–L4) were visualized on lateral radiographs and severity was graded by a validated scoring system. Measurements were performed at baseline and at years 1, 2, and 3. At baseline, there was a significant inverse correlation between the severity of AC and BMD at the hip (r=−0.151, P=0.003), but not at the lumbar spine. The two oral doses and the 1.0 mg IV dose evoked statistically significant increases in both hip and spine BMD compared with placebo, whereas the effect of 0.5 mg was significant only at the hip (P<0.05). No differences in the yearly rate of progression or the 3-year change in AC was observed between the different intervention groups. Furthermore, there were no statistically significant correlations between the 3-year change in BMD and the simultaneous change in AC. These findings thus suggest that 3-year treatment with effective doses of ibandronate does not pose any cardiovascular risk in terms of altering vascular calcification.
Literature
1.
go back to reference von der Recke P, Hansen MA, Hassager C (1999) The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 106:273–278CrossRefPubMed von der Recke P, Hansen MA, Hassager C (1999) The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 106:273–278CrossRefPubMed
2.
go back to reference Van Der Klift M, Pols HA, Hak AE, Witteman JC, Hofman A, De Laet CE (2002) Bone mineral density and the risk of peripheral arterial disease: the Rotterdam study. Calcif Tissue Int 70:443–449CrossRefPubMed Van Der Klift M, Pols HA, Hak AE, Witteman JC, Hofman A, De Laet CE (2002) Bone mineral density and the risk of peripheral arterial disease: the Rotterdam study. Calcif Tissue Int 70:443–449CrossRefPubMed
3.
go back to reference Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–289PubMed Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–289PubMed
4.
go back to reference Tankó LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20 Tankó LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20
5.
go back to reference Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW (2001) Bone loss and the progression of abdominal aortic calcification over a 25-year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276PubMed Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW (2001) Bone loss and the progression of abdominal aortic calcification over a 25-year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276PubMed
6.
go back to reference Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931PubMed Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931PubMed
7.
go back to reference Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–289PubMed Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–289PubMed
8.
go back to reference Mody N, Tintut Y, Radcliff K, Demer LL (2003) Vascular calcification and its relation to bone calcification: possible underlying mechanisms. J Nucl Cardiol 10:177–183CrossRefPubMed Mody N, Tintut Y, Radcliff K, Demer LL (2003) Vascular calcification and its relation to bone calcification: possible underlying mechanisms. J Nucl Cardiol 10:177–183CrossRefPubMed
9.
go back to reference Burnett JR, Vasikaran SD (2002) Cardiovascular disease and osteoporosis: is there a link between lipids and bone? Ann Clin Biochem 39:203–210CrossRefPubMed Burnett JR, Vasikaran SD (2002) Cardiovascular disease and osteoporosis: is there a link between lipids and bone? Ann Clin Biochem 39:203–210CrossRefPubMed
10.
go back to reference Rossouw JE, Anderson GL, Prentice RL et al. (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333PubMed Rossouw JE, Anderson GL, Prentice RL et al. (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333PubMed
11.
go back to reference Watts NB (2003) Bisphosphonate treatment of osteoporosis. Clin Geriatr Med 19:395–414PubMed Watts NB (2003) Bisphosphonate treatment of osteoporosis. Clin Geriatr Med 19:395–414PubMed
12.
go back to reference Papapoulos SE (2003) Ibandronate: a potent new bisphosphonate in the management of postmenopausal osteoporosis. Int J Clin Pract 57:417–422PubMed Papapoulos SE (2003) Ibandronate: a potent new bisphosphonate in the management of postmenopausal osteoporosis. Int J Clin Pract 57:417–422PubMed
13.
go back to reference Fleisch H (ed) (2000) Bisphosphonates in bone disease. From laboratory to the patients. Academic Press, San Diego—San Francisco—New York—Boston—London—Sydney—Tokyo Fleisch H (ed) (2000) Bisphosphonates in bone disease. From laboratory to the patients. Academic Press, San Diego—San Francisco—New York—Boston—London—Sydney—Tokyo
15.
go back to reference Zaidi M, Fallon JT (2003) Oral bisphosphonates induce aortic root inflammation and plaque rupture in an apoE knock out mouse. J Bone Miner Res 18:S264 Zaidi M, Fallon JT (2003) Oral bisphosphonates induce aortic root inflammation and plaque rupture in an apoE knock out mouse. J Bone Miner Res 18:S264
16.
go back to reference Goldstein MR (1999) Long-term therapy for postmenopausal osteoporosis: stronger bones but weaker arteries. Circulation 100:446–447 Goldstein MR (1999) Long-term therapy for postmenopausal osteoporosis: stronger bones but weaker arteries. Circulation 100:446–447
17.
go back to reference Goldstein MR (2000) Bisphosphonate therapy and vascular calcification. JAMA 283:1424–1425CrossRef Goldstein MR (2000) Bisphosphonate therapy and vascular calcification. JAMA 283:1424–1425CrossRef
18.
go back to reference Price PA, Faus SA, Williamson MK (2001) Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. Arterioscler Thromb Vasc Biol 21:817–824 Price PA, Faus SA, Williamson MK (2001) Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. Arterioscler Thromb Vasc Biol 21:817–824
19.
go back to reference Burke AP, Taylor A, Farb A, Malcom GT, Virmani R (2000) Coronary calcification: insights from sudden coronary death victims. Z Kardiol 89:49–53CrossRefPubMed Burke AP, Taylor A, Farb A, Malcom GT, Virmani R (2000) Coronary calcification: insights from sudden coronary death victims. Z Kardiol 89:49–53CrossRefPubMed
20.
go back to reference Delmas PD, Recker RR, Chesnut CH 3rd, Skag A, Stakkestad JA, Emkey R, Gilbride J, Schimmer RC, Christiansen C (2004) Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporos Int 2004 Apr 8 (epub ahead of publication) Delmas PD, Recker RR, Chesnut CH 3rd, Skag A, Stakkestad JA, Emkey R, Gilbride J, Schimmer RC, Christiansen C (2004) Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporos Int 2004 Apr 8 (epub ahead of publication)
21.
go back to reference Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW (1997) New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 132:245–250CrossRefPubMed Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW (1997) New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 132:245–250CrossRefPubMed
22.
go back to reference Bagger YZ, Tankó LB, Alexandersen P, Ravn P, Christiansen C (2003) Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal. Bone 33:301–307CrossRefPubMed Bagger YZ, Tankó LB, Alexandersen P, Ravn P, Christiansen C (2003) Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal. Bone 33:301–307CrossRefPubMed
23.
go back to reference Simon A, Giral P, Levenson J (1995) Extracoronary atherosclerotic plaque at multiple sites and total coronary calcification deposit in asymptomatic men. Association with coronary risk profile. Circulation 92:1414–1421 Simon A, Giral P, Levenson J (1995) Extracoronary atherosclerotic plaque at multiple sites and total coronary calcification deposit in asymptomatic men. Association with coronary risk profile. Circulation 92:1414–1421
24.
go back to reference Fazio GP, Redberg RF, Winslow T, Schiller NB (1993) Transesophageal echocardio-graphically detected atherosclerotic aortic plaque is a marker for coronary artery disease. J Am Coll Cardiol 21:144–150PubMed Fazio GP, Redberg RF, Winslow T, Schiller NB (1993) Transesophageal echocardio-graphically detected atherosclerotic aortic plaque is a marker for coronary artery disease. J Am Coll Cardiol 21:144–150PubMed
25.
go back to reference Bots ML, Witteman JC, Grobbee DE (1993) Carotid intima-media wall thickness in elderly women with and without atherosclerosis of the abdominal aorta. Atherosclerosis 102:99–105PubMed Bots ML, Witteman JC, Grobbee DE (1993) Carotid intima-media wall thickness in elderly women with and without atherosclerosis of the abdominal aorta. Atherosclerosis 102:99–105PubMed
26.
go back to reference Tankó LB, Mouritzen U, Lehmann HJ, Warming L, Moelgaard A, Christgau S, Qvist P, Baumann M, Wieczorek L, Hoyle N, Christiansen C (2003) Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens. Bone 32:687–693CrossRefPubMed Tankó LB, Mouritzen U, Lehmann HJ, Warming L, Moelgaard A, Christgau S, Qvist P, Baumann M, Wieczorek L, Hoyle N, Christiansen C (2003) Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens. Bone 32:687–693CrossRefPubMed
27.
go back to reference Stakkestad JA, Benevolenskaya LI, Stepan JJ, Skag A, Nordby A, Oefjord E, Burdeska A, Jonkanski I, Mahoney P (2003) Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women. Ann Rheum Dis 62:969–975CrossRefPubMed Stakkestad JA, Benevolenskaya LI, Stepan JJ, Skag A, Nordby A, Oefjord E, Burdeska A, Jonkanski I, Mahoney P (2003) Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women. Ann Rheum Dis 62:969–975CrossRefPubMed
28.
go back to reference Smith JA, Vento JA, Spencer RP, Tendler BE (1999) Aortic calcification contributing to bone densitometry measurement. J Clin Densitom 2:181–183PubMed Smith JA, Vento JA, Spencer RP, Tendler BE (1999) Aortic calcification contributing to bone densitometry measurement. J Clin Densitom 2:181–183PubMed
29.
go back to reference Hill JA, Goldin JG, Gjertson D, Emerick AM, Greaser LD, Yoon HC, Khorrami S, Aziz D, Adams JS (2002) Progression of coronary artery calcification in patients taking alendronate for osteoporosis. Acad Radiol 9:1148–1152CrossRefPubMed Hill JA, Goldin JG, Gjertson D, Emerick AM, Greaser LD, Yoon HC, Khorrami S, Aziz D, Adams JS (2002) Progression of coronary artery calcification in patients taking alendronate for osteoporosis. Acad Radiol 9:1148–1152CrossRefPubMed
Metadata
Title
Effective doses of ibandronate do not influence the 3-year progression of aortic calcification in elderly osteoporotic women
Authors
László B. Tankó
Gerong Qin
Peter Alexandersen
Yu Z. Bagger
Claus Christiansen
Publication date
01-02-2005
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 2/2005
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-004-1662-x

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