Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption.
Abstract
Abstract —The present experiments were carried out to test the hypothesis that artery calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with the bisphosphonates alendronate and ibandronate will inhibit artery calcification. Artery calcification was first induced by treatment of 42-day-old male rats with warfarin, a procedure that inhibits the γ-carboxylation of matrix Gla protein and has been shown to cause extensive calcification of the artery media within 2 weeks. These experiments revealed that ibandronate (0.05 mg · kg −1 · d −1 ) and alendronate (0.1 mg · kg −1 · d −1 ) completely inhibited calcification of all arteries and heart valves examined after 2 and 4 weeks of warfarin treatment. A 10-fold lower dose of alendronate reduced artery calcification by 50% ( P <0.005). These bisphosphonate doses are comparable to those that inhibit bone resorption in rats of this age. More rapid artery calcification was induced by treatment with warfarin together with high doses of vitamin D, a procedure that causes extensive artery calcification by 84 hours. Alendronate and ibandronate again completely inhibited calcification of all arteries and heart valves examined. The subcutaneous doses of alendronate and ibandronate necessary to inhibit artery calcification are comparable to the daily subcutaneous doses of these drugs that have previously been shown to inhibit bone resorption in rats of the same age, with 50% inhibition of artery calcification at 20 μg alendronate · kg −1 · d −1 and at 1 μg ibandronate · kg −1 · d −1 . Bisphosphonate treatment did not affect serum calcium and phosphate, and so the inhibition of artery calcification cannot be due to a simple lowering of the serum calcium phosphate ion product. We conclude that bisphosphonates inhibit the calcification of arteries and heart valves at doses comparable to the doses that inhibit bone resorption. These results support the hypothesis that artery calcification is linked to bone resorption. The mechanism of this linkage remains to be established, however, and an alternative explanation for the present results is also considered.
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Bisphosphonate treatment suppresses vascular calcification in the rat warfarin model, associated with bone turnover suppression.
“Bisphosphonate treatment of rats also suppressed vascular calcification in this warfarin model, in association with bone turnover suppression (145).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [145]
Although OPG and bisphosphonates have opposite effects on endothelial cell survival, both suppress bone turnover and prevent vascular calcification in a similar animal model.
“Thus, although OPG and bisphosphonates can have opposite effects on the survival of endothelial cells, both agents suppress bone turnover and prevent vascular calcification when tested in a similar animal model (144, 145).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [145]
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Self-citation
- Authors
- Price, P. A., Faus, S. A., & Williamson, M. K.
- Affiliations
- University of California San Diego (US)
- ORCID
- Price, Paul A.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2001-05
- Volume
- 21
- Issue
- 5
- Pages
- 817-824
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2062776506
- Cited by
- 301
- References
- 33
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 9 · 2018: 4 · 2017: 10 · 2016: 11 · 2015: 11 · 2014: 8 · 2013: 17 · 2012: 17
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL058090, HL-58090)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- bisphosphonates, alendronate, ibandronate, vascular calcification, arterial calcification, cardiac valve calcification, bone resorption, warfarin, matrix Gla protein, vitamin D, calcification inhibition
- MeSH terms
- Ibandronic Acid, Animals, Aortic Diseases, Bone Resorption, Calcification, Physiologic, Calcinosis, Diphosphonates, Drug Administration Schedule, Female, Humans, Male, Muscle, Smooth, Vascular, Osteoporosis, Etidronic Acid, Vitamin D, Warfarin, Rats, Sprague-Dawley, Alendronate, Rats
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