Abdominal Aortic Calcification, BMD, and Bone Microstructure: A Population-Based Study

Chow, John T.; Khosla, Sundeep; Melton, L. Joseph; Atkinson, Elizabeth J.; Camp, Jon J.; Kearns, Ann E.

doi:10.1359/jbmr.080504

Cited by 47 publications

(24 citation statements)

References 89 publications

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“…Though limited by the cross-sectional nature of the analysis, this methodology and the reduction in beta estimate we found in our cohort suggest possible causal pathways between variables 19 . This process may particularly apply to the elderly, who are more likely to suffer from weight loss, bone demineralization and vascular calcification 40, 41 . In accordance with this concept, we found a borderline interaction between BMD and age (p=0.07), and after appropriate stratification the role of BMD was confirmed only for individuals older than 68 years of age.…”

Section: Discussionmentioning

confidence: 99%

Role of bone mineral density in the inverse relationship between body size and aortic calcification: Results from the Baltimore Longitudinal Study of Aging

et al. 2014

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OBJECTIVE There is a J-shaped relationship between body mass index (BMI) and cardiovascular outcomes in elderly patients (obesity paradox). Whether low BMI correlates with aortic calcification (AC) and whether this association is accounted for by bone demineralization is uncertain. METHODS Presence of AC was evaluated in 687 community-dwelling individuals (49% male, mean age 67±13 years) using CT images of the thoracic, upper and lower abdominal aorta, and scored from 0 to 3 according to number of sites that showed any calcification. Whole-body bone mineral density (BMD) was evaluated by dual-energy x-ray absorptiometry. Predictors of AC were assessed by logistic regression, and the role of BMD using mediation analysis. RESULTS Age and cardiovascular risk factors were positively associated while both BMI (r=−0.11, p<0.01) and BMD (r=−0.17, p<0.0001) were negatively associated with AC severity. In multivariate models, lower BMI (OR 0.96, 95%CI 0.92–0.99, p=0.01), older age, higher systolic blood pressure, use of lipid-lowering drugs and smoking were independent predictors of AC. A nonlinear relationship between BMI and AC was noticed (p=0.03), with decreased AC severity among overweight participants. After adjusting for BMD, the coefficient relating BMI to AC was reduced by 14% and was no longer significant, whereas BMD remained negatively associated with AC (OR 0.82, 95%CI 0.069–0.96, p=0.01), with a trend for a stronger relationship in older participants. CONCLUSION Low BMI is associated with increased AC, possibly through calcium mobilization from bone, resulting in low BMD. Prevention of weight loss and bone demineralization with aging may help reducing AC.

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Section: Discussionmentioning

confidence: 99%

Role of bone mineral density in the inverse relationship between body size and aortic calcification: Results from the Baltimore Longitudinal Study of Aging

et al. 2014

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“…32,48 A large number of studies demonstrated a relationship between vascular disease and bone pathology. 4 The coexistence of osteoporosis and vascular calcification has been consistently demonstrated in postmenopausal women and elderly people 49 and also in patients with CKD. 50 This bonevascular axis involves bone-derived proteins that regulate vascular calcification and proteins of vascular origin that regulate bone metabolism.…”

Section: Wnt Inhibitors and The Kidney-bone-vascular Axismentioning

confidence: 99%

Sclerostin and DKK1: new players in renal bone and vascular disease

Evenepoel

D’Haese

Brandenburg

2015

Kidney International

125

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For more than a decade, the Wnt-β-catenin pathway has been the focus of intense basic and clinical research in the bone field because of its importance in skeletal development and maintenance of bone mass. Wnt activation increases bone formation and decreases bone resorption. The Wnt-β-catenin signaling pathway is tightly regulated by several inhibitors, among which Dickkopf-related protein 1 (DKK1) and sclerostin have been most comprehensively studied. Mounting evidence indicates that a disturbed Wnt-β-catenin signaling is also implicated in the pathogenesis of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD) and affects its various components. DKK1 and sclerostin, more specifically, may be involved in the intense cross-talk between the kidneys, vasculature, and bone. Studies exploring clinical correlates of circulating sclerostin and DKK1 levels so far yielded conflicting results. Biological variability and analytical issues account at least partly for this inconsistency. Antibodies neutralizing Wnt inhibitors may be an appealing strategy to prevent or treat CKD-MBD. Caution is however warranted as sclerostin not only opposes mineralization in the bone but possibly also in the vasculature. Additional studies are required to define determinants of Wnt inhibitors in CKD and to evaluate the efficacy and safety of recently introduced pharmaceuticals targeting these inhibitors.

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“…Dual-energy x-ray absorptiometry (DXA) and central quantitative computed tomography (QCT) can be used to simultaneously quantify BMD and AAC [18, 19]. Although DXA is considered as current clinical gold standard for the diagnosis of osteoporosis and the assessment of fracture risk, this technique has certain limitations.…”

Section: Introductionmentioning

confidence: 99%

Quantification of lower leg arterial calcifications by high-resolution peripheral quantitative computed tomography

Patsch

Zulliger

Vilayphou

et al. 2014

Bone

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Vascular calcifications and bone health seem to be etiologically linked via common risk factors such as aging and subclinical chronic inflammation. Epidemiologic studies have shown significant associations between low bone mineral density (BMD), fragility fractures and calcifications of the coronary arteries and the abdominal aorta. In the last decade, high-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as in-vivo research tool for the assessment of peripheral bone geometry, density, and microarchitecture. Although vascular calcifications are frequently observed as incidental findings in HR-pQCT scans, they have not yet been incorporated into quantitative HR-pQCT analyses. We developed a semi-automated algorithm to quantify lower leg arterial calcifications (LLAC), captured by HR-pQCT. The objective of our study was to determine validity and reliability of the LLAC measure. HR-pQCT scans were downscaled to a voxel size of 250 µm. After subtraction of bone volumes from the scans, LLAC were detected and contoured by a semi-automated, dual-threshold seed-point segmentation. LLAC mass (in mg hydroxyapatite; HA) was calculated as the product of voxel-based calcification volume (mm3) and mean calcification density (mgHA/cm3)/1000. To determine validity, we compared LLAC to coronary artery calcifications (CAC), as quantified by multi-detector computed tomography (MDCT) and Agatston scoring in forty-six patients on chronic hemodialysis. Moreover, we investigated associations of LLAC with age, time on dialysis, type-2 diabetes mellitus, history of stroke, and myocardial infarction. In a second step, we determined intra- and inter-reader reliability of the LLAC measure. In the validity study, LLAC were present (>0 mgHA) in 76% of patients, 78% of patients had CAC (>0 mgHA). Median LLAC was 6.65 (0.08 – 24.40) mgHA and median CAC as expressed by Agatston score was 266.3 (15.88 – 1877.28). We found a significant positive correlation between LLAC and CAC (rho=0.6; p<0.01). Dialysis patients with type-2 diabetes mellitus (DM; 35%) and history of stroke (13%) had higher median LLAC than patients without those conditions (DM 20.0 fold greater, p=0.006; Stroke 5.1 fold greater, p=0.047;). LLAC was positively correlated with time on dialysis (rho=0.337, p=0.029), there was a trend towards a positive association of LLAC and age (rho=0.289, p=0.053). The reliability study yielded excellent intra- and inter-reader agreement of the LLAC measure (intra-reader ICC=0.999, 95% CI=0.998–1.000; inter-reader ICC=0.998, 95% CI=0.994–0.999). Our study indicates that the LLAC measure has good validity and excellent reliability. The use of HR-pQCT for the simultaneous evaluation of arterial calcifications, peripheral bone geometry, bone density, and bone microarchitecture should facilitate future research on osteo-vascular interactions and potential associations with cardiovascular events.

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Abdominal Aortic Calcification, BMD, and Bone Microstructure: A Population-Based Study

Cited by 47 publications

References 89 publications

Role of bone mineral density in the inverse relationship between body size and aortic calcification: Results from the Baltimore Longitudinal Study of Aging

Role of bone mineral density in the inverse relationship between body size and aortic calcification: Results from the Baltimore Longitudinal Study of Aging

Sclerostin and DKK1: new players in renal bone and vascular disease

Quantification of lower leg arterial calcifications by high-resolution peripheral quantitative computed tomography

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