Progression of Coronary Artery Calcification in Patients Taking Alendronate for Osteoporosis

Hill, Jennifer G.; Goldin, Jonathan G.; Gjertson, David W.; Emerick, Aletha; Greaser, Lloyd D.; Yoon, Hyo‐Chun; Khorrami, Shauna; Aziz, Donya; Adams, John S.

doi:10.1016/s1076-6332(03)80516-0

Cited by 35 publications

(24 citation statements)

References 13 publications

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“…(44) Neither our analysis nor that of the parent study found any association between clodronate treatment and incident cardiovascular disease. Our study was not designed to specifically test the hypothesis that clodronate may reduce incident stroke or MI.…”

Section: Discussioncontrasting

confidence: 61%

Abdominal Aortic Calcification Detected on Lateral Spine Images From a Bone Densitometer Predicts Incident Myocardial Infarction or Stroke in Older Women

Schousboe

Taylor

Kiel

et al. 2008

Journal of Bone and Mineral Research

115

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Among a cohort of elderly women, abdominal aortic calcification scored on baseline lateral spine densitometric images intended for vertebral fracture assessment was associated with subsequent myocardial infarction or stroke over a median 4-yr period, independent of clinical cardiovascular disease risk factors.Introduction: Cardiovascular disease (CVD) risk among older women is not adequately captured by traditional CVD risk factors. Lateral spine images obtained on bone densitometers for vertebral fracture assessment (VFA) can detect abdominal aortic calcification (AAC), an important marker of subclinical CVD. Our objective was to estimate the association between AAC scored on VFA images and subsequent myocardial infarction (MI) or stroke in elderly women. Materials and Methods: Among participants in a randomized controlled trial (women; age >75 yr) of clodronate versus placebo, those who sustained an MI or stroke during the median 4-yr follow-up study period were selected as cases (n ‫ס‬ 408), and 408 controls were randomly selected from the remainder of the parent study population. Baseline VFA images were scored for AAC with a previously validated 24-point scale and a newer, simpler 8-point scale.Results: The OR of incident MI or stroke for those in the middle and top tertiles, respectively, compared with the bottom tertile of AAC score were 1.14 (95% CI, 0.79-1.66) and 1.74 (95% CI, 1.19-2.56) for the 24-point scale and 1.42 (95% CI, 0.98-2.05) and 1.77 (95% CI, 1.22-2.55) for the 8-point scale, adjusted for age, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, blood pressure, smoking, renal function, health status, and baseline diagnoses of diabetes mellitus, hypertension, angina, and prior stroke. Conclusions: AAC scored on VFA images is independently associated with incident MI or stroke. Because bone densitometry is indicated for all women Ն65 yr of age, VFA imaging offers an opportunity to capture this CVD risk factor in postmenopausal women undergoing bone densitometry at very little additional cost.

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Section: Discussioncontrasting

confidence: 61%

Abdominal Aortic Calcification Detected on Lateral Spine Images From a Bone Densitometer Predicts Incident Myocardial Infarction or Stroke in Older Women

Schousboe

Taylor

Kiel

et al. 2008

Journal of Bone and Mineral Research

115

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“…Preliminary evidence in humans with CKD confirms these findings and randomized controlled trials evaluating this outcome are in progress [46]. …”

Section: Comparing Studies In Animal Models To Clinical Trials In Hummentioning

confidence: 78%

Vascular Calcification in Animal Models of CKD: A Review

Shobeiri¹,

Adams²,

2010

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Vascular calcification is a significant contributor to the cardiovascular mortality observed in chronic kidney disease (CKD). This review discusses the animal models (5/6 nephrectomy, mouse electrocautery model and dietary adenine) that have been employed in the study of vascular calcification outcomes in CKD. Rodent models of CKD generate a range of severity in the vascular calcification phenotype. Major limitations of the 5/6th nephrectomy model include the requirement for surgery and the need to use either excessive dietary phosphorus or vitamin D. Major limitations of the mouse electrocautery model include the requirement for surgery, the mortality rate when very advanced CKD develops, and resistance to vascular calcification without the use of transgenic animals. This is balanced against the major advantage of the ability to study transgenic animals to further understand the mechanisms associated with either the acceleration or inhibition of calcification. Dietary adenine generates severe CKD and does not require surgery. The major disadvantage is the weight loss that ensues when rats receive a diet containing 0.75% adenine. In summary, animal models are useful to study CKD-associated vascular calcification and the results obtained in these pre-clinical animal studies appear to translate to the evidence, however limited, which exists in humans with CKD.

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“…It was found that only etidronate was effective in reducing vascular calcification and atherosclerosis, [14][15][16] whereas other bisphosphonates barely had any effects. [17][18][19] In the preliminary trial, we assigned patients with hypercholesterolemia to the atorvastatin group or the atorvastatin plus etidronate combination therapy group and treated them for 12 months. As a result, the combination therapy group and the atorvastatin group had reduced maximal vessel wall thickness of the thoracic aorta (−15%; 95% confidence interval [CI], −18.5 to −11.5; and 14%; 95% CI, −17.3 to −10.6, respectively).…”

Section: Clinical Perspective On P 2335mentioning

confidence: 99%

Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques

et al. 2013

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Background-Statins are not effective in reducing atherosclerotic plaques of the abdominal aorta, and accumulating evidence suggests that bisphosphonates have the potential to induce the regression of atherosclerotic plaques of the abdominal aorta. Methods and Results-A prospective, randomized, open-label, blinded-end-point trial involving 108 participants with hypercholesterolemia was conducted. Participants received 20 mg atorvastatin daily, 400 mg etidronate daily, or both drugs daily. The primary end point was the percent change in maximal vessel wall thickness of atherosclerotic plaques in the thoracic and abdominal aortas as measured by magnetic resonance imaging after 12 months of treatment. In both the combination therapy and atorvastatin groups, maximal vessel wall thickness of the thoracic aorta was reduced by 13.8% (95% confidence interval, −16.4 to −11.3) and 12.3% (95% confidence interval, −14.9 to −9.7), respectively. These reduction rates were comparable between groups (P=0.61). Meanwhile, in the etidronate group, maximal vessel wall thickness of the thoracic aorta remained unchanged (2.2%; 95% confidence interval, −0.3 to 4.8). Conversely, maximal vessel wall thickness of the abdominal aorta was reduced more effectively in the combination therapy group (−11.4%) than in the atorvastatin group (−0.9%; P<0.001) and the etidronate group (5.5%; P=0.006). Conclusions-Atorvastatin plus etidronate combination therapy for 12 months significantly reduced both thoracic and abdominal aortic plaques, whereas atorvastatin monotherapy reduced only thoracic aortic plaques and etidronate monotherapy reduced only abdominal aortic plaques. The effectiveness of combination therapy in reducing atherosclerotic plaques in the abdominal aorta was significantly greater than for both atorvastatin and etidronate monotherapy.

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Progression of Coronary Artery Calcification in Patients Taking Alendronate for Osteoporosis

Cited by 35 publications

References 13 publications

Abdominal Aortic Calcification Detected on Lateral Spine Images From a Bone Densitometer Predicts Incident Myocardial Infarction or Stroke in Older Women

Abdominal Aortic Calcification Detected on Lateral Spine Images From a Bone Densitometer Predicts Incident Myocardial Infarction or Stroke in Older Women

Vascular Calcification in Animal Models of CKD: A Review

Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques

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