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      Vascular Effects of Bisphosphonates—A Systematic Review

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          Abstract

          Background:

          Osteoporosis and cardiovascular disease are interconnected entities with pathophysiological similarities. Bisphosphonates are therapeutic options available for resorptive bone diseases; however, experimental evidence has demonstrated a role for bisphosphonates in the inhibition of atherogenesis.

          Methods:

          A systematic review of the vascular effects of bisphosphonates on atherosclerosis was performed. Vascular effects were evaluated by the thickening of the intima-media of carotid arteries and calcification of the coronary and aorta arteries. Electronic databases PubMed, The Cochrane Library, and Embase from January 1980 to May 2011 were searched.

          Results:

          Of 169 potentially relevant articles, 9 clinical trials were selected. Two articles showed the benefit of the use of etidronate (−0.038 mm, P < 0.005) and alendronate (−0.025 mm, P < 0.05) on carotid artery intima-media thickening (CIMT) after one year. One article found no changes associated with the use of alendronate. The use of risedronate was associated with a reduction of plaque score on the carotid arteries (decrease of 1% at 1 year, P = 0.015). Of those studies that evaluated the effect on coronary artery calcification (CAC), the results are conflicting: one study showed no changes with use of etidronate and in another, etidronate resulted in inhibition of the process of CAC after 1 year of follow-up (−372 mm 3 in CAC score, P < 0.01). Three studies showed positive effects of etidronate on the aortic calcificaton (AC) score, showing no effect with use of ibandronate, and another showed a inhibition in the progression of the abdominal AC score with use of risendronate ( P = 0.043).

          Conclusion:

          Bisphosphonates seem to have an inhibitory effect on the atherosclerotic process; however, larger placebo-controlled studies are needed to better clarify this issue.

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          Most cited references42

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          Bisphosphonates: mechanisms of action.

          H Fleisch (1998)
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            Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation.

            To assess the reliability of electron beam computed tomography (CT) in the detection of calcific deposits in coronary arteries. The authors quantitatively evaluated a total of 4,298 segments of coronary arteries with electron beam CT and histomorphometry. Regression analysis of the electron beam CT calcium score versus histomorphometric calcium area produced an r2 value of .92 (r = .96; P < .0001). Ninety-three percent (78 of 84) of all coronary arteries with stenosis of 76%-100% contained calcific deposits, and 20% (17 of 83) of all coronary arteries with stenosis of 0%-50% contained calcific deposits. The amount of calcific deposits detected with electron beam CT correlates highly with histomorphometric measurements. Also, the amount of calcific deposits correlates well with the degree of coronary artery stenosis. Electron beam CT, therefore, is a promising noninvasive technique that can help depict the presence and extent of atherosclerotic plaques.
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              The association between low bone mass at the menopause and cardiovascular mortality.

              Low bone mineral density in late postmenopausal women has been associated with increased nontrauma mortality. We investigated whether bone mass in women soon after menopause was also associated with the risk of mortality in later life. Between 1977 and 1988, two samples of healthy women were enrolled; one group soon after the menopause (age 50 +/- 2 years [mean +/- SD], n = 309) and another later after menopause (age 70 +/- 2 years, n = 754). The baseline visit included a medical examination and a measurement of bone mineral content in the distal forearm. In 1994, vital status was checked. All causes of death were registered, excluding those that were due to trauma or suicide. Multivariate relative risks (RR) and 95% confidence intervals (CI) were determined. In the early postmenopausal group, each decrease of one SD (0.4 g/cm) in bone mineral content was associated with a 43% increase in mortality (RR = 1.4; 95% CI 1.0 to 2.0; P < 0.05). When only cardiovascular death was considered, the relative risk of dying within 17 years of the menopause was increased 2.3-fold (95% CI 1.0 to 5.3; P < 0.05). Correspondingly, a 70-year-old woman with a bone mineral content 1 SD below the mean for her age had a 1.8-fold increased risk of dying from cardiovascular disease (95% CI 1.0 to 3.2; P = 0.06). Expressed as quartiles, women with bone mass in the lowest quartile had twice the risk of cardiovascular death compared with those in the highest quartile. A prevalent vertebral compression fracture in the late postmenopausal group was independently associated with cardiovascular death (RR = 2.0; 95% CI 1.4 to 3.3; P = 0.004). Low bone mineral content at the menopause is a risk factor for increased mortality in later life, especially from cardiovascular disease.
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                Author and article information

                Journal
                Clin Med Insights Endocrinol Diabetes
                Clin Med Insights Endocrinol Diabetes
                Clinical Medicine Insights. Endocrinology and Diabetes
                Libertas Academica
                1179-5514
                2012
                25 October 2012
                : 5
                : 47-54
                Affiliations
                Division of Endocrinology and Diabetes, Agamenon Magalhães Hospital, Ministry of Health, University of Pernambuco Medical School, Recife, Brazil.
                Author notes
                Corresponding author email: leynaleite@ 123456yahoo.com.br
                Article
                cmed-5-2012-047
                10.4137/CMED.S10007
                3486790
                23133318
                3b6cc755-1f75-46f9-90ea-68beb5c6157d
                © the author(s), publisher and licensee Libertas Academica Ltd.

                This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.

                History
                Categories
                Consise Review

                Endocrinology & Diabetes
                carotid imt,osteoporosis,aortic calcification,bisphosphonates,atherosclerosis

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