Arterial Calcifications and Bone Histomorphometry in End-Stage Renal Disease

London, Gérard M.; Marty, Caroline; Marchais, Sylvain J.; Guérin, Alain P.; Mëtivier, Fabien; Vernejoul, M. C. De

doi:10.1097/01.asn.0000129337.50739.48

Cited by 543 publications

(443 citation statements)

References 41 publications

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“…The absence of correlations between histomorphometric indexes of bone turnover and coronary calcifications differ from reports by London et al (13,14), who found an association between systemic arterial calcifications (aorta and the main peripheral arteries) and indexes of low bone turnover, but not trabecular volume. One important difference between these publications resides in the arterial territories analyzed and the relationships of the different bone changes (bone volume, osteoblasts number, or tetracycline labeling), which do not necessarily reflect the same mechanisms.…”

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confidence: 55%

“…In dialysis patients, coronary artery calcification score was found to be inversely correlated with vertebral bone mass (11,12). In addition, a high systemic arterial calcification score combined with bone histomorphometry suggestive of low bone activity was observed in hemodialysis patients (13,14). Arterial stiffening and low spine BMD or calcaneal osteopenia were significantly associated in CKD and hemodialysis patients (15)(16)(17).…”

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confidence: 86%

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Bone–Vascular Axis in Chronic Kidney Disease

London¹

2009

Clinical Journal of the American Society of Nephrology

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C hronic kidney disease (CKD) is characterized by changes in mineral metabolism associated with alterations of its hormonal regulation and various forms of bone disease. In the past, these associations focused attention on the kidney-bone axis. The last decade has seen renewed interest on interactions among mineral metabolism disorders and extraosseous and cardiovascular calcifications observed in CKD or end-stage renal disease (ESRD). Vascular calcification is an active process similar to bone formation that implicates a variety of proteins involved in bone and mineral metabolism (1,2) and is considered part of a systemic dysfunction defined as CKD-mineral and bone disorder (3). Growing evidence linking bone with different functional and structural characteristics of the arterial tree has contributed to developing the concept of the bone-vascular axis (4).The first observations suggesting the existence of the bonevascular axis were the frequent associations of osteoporosis and atherosclerotic vascular calcifications observed in postmenopausal women (5-7). Longitudinal population-based studies revealed a relationship between the progression of vascular calcifications and bone demineralization, and others were identified between bone mineral density (BMD) and aortic or central artery calcifications (6), or coronary arteries in type 2 diabetes (8). The osteopenia-osteoporosis association was also linked with arterial functional indexes, such as aortic stiffness and interactions independent of calcifications, suggesting broader biologic interplay (9,10).Relationships between bone and vascular modifications were also observed in CKD and ESRD patients. In dialysis patients, coronary artery calcification score was found to be inversely correlated with vertebral bone mass (11,12). In addition, a high systemic arterial calcification score combined with bone histomorphometry suggestive of low bone activity was observed in hemodialysis patients (13,14). Arterial stiffening and low spine BMD or calcaneal osteopenia were significantly associated in CKD and hemodialysis patients (15)(16)(17).In the present issue of the Journal, Adragao et al. (18) provide new evidence linking altered bone metabolism to coronary calcifications in patients with stage-5 CKD on hemodialysis. In their cross-sectional study performed on 38 hemodialyzed patients, they analyzed the relationships between bone biopsy parameters (bone volume/total volume, bone formation rate/ bone surface, and activation frequency) and coronary calcifications determined by multislide computer tomography. Their principal conclusion was that low bone volume is associated with more coronary calcifications, whereas histomorphometric parameters of bone turnover were independent of coronary calcifications.Their results complete those of Barreto et al. (12), who found a negative correlation between coronary calcifications and trabecular bone volume or its thickness. The absence of correlations between histomorphometric indexes of bone turnover and coronary calcifications dif...

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confidence: 86%

Bone–Vascular Axis in Chronic Kidney Disease

London¹

2009

Clinical Journal of the American Society of Nephrology

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“…(5)(6)(7)(8) Importantly, deviation from the normal range of serum bone biomarkers predicts an increased risk of cardiovascular events, (9) and impaired bone remodeling is associated with increased vascular calcification. (10) In the general population, individuals with osteoporosis have increased atherosclerosis and coronary artery calcification (11)(12)(13)(14) and there is an inverse relationship between coronary artery calcification and bone mineral density (BMD) in both normal and CKD patients. (15) Agents that enhance bone quality also reduce cardiovascular calcification.…”

Section: Introductionmentioning

confidence: 99%

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Sabbagh

Graciolli

O’Brien

et al. 2012

Journal of Bone and Mineral Research

240

224

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Chronic kidney disease–mineral bone disorder (CKD‐MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft‐tissue calcification. Emerging evidence suggests that features of CKD‐MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild‐type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD‐MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild‐type mice. To capture the early molecular and cellular events in the progression of CKD‐MBD we examined cell‐specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor‐Ser33/37‐β‐catenin was observed both in mouse and human bones. Overall repression of Wnt/β‐catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF‐κB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late‐stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD‐MBD and suggest that repression of the Wnt/β‐catenin pathway is involved in the pathogenesis of renal osteodystrophy. © 2012 American Society for Bone and Mineral Research.

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“…The evidences linking bone disease to vascular calcification in CKD patients have been based on bone turnover derangements and not on bone density. In studies with bone biopsy, an association between CAC and low bone turnover has been observed in CKD patients (17,34,35). It seems that the decreased bone formation rate leads to an inability of bone to buffer the calcium overload, predisposing to metastatic calcification (36).…”

Section: Discussionmentioning

confidence: 99%

Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

Filgueira

Carvalho

Tomiyama

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD.Design, setting, participants, & measurements Seventy-two nondialyzed CKD patients (age 52 Ϯ 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 Ϯ 18.2 ml/min per 1.73 m 2 ) were studied. VBD and CAC were quantified by computed tomography.Results CAC Ͼ 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score Ն 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 Ϯ 52 Hounsfield units) correlated inversely with age (r ϭ Ϫ0.41, P Ͻ 0.001) and calcium score (r ϭ Ϫ0.31, P ϭ 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC.Conclusions Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD.

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Arterial Calcifications and Bone Histomorphometry in End-Stage Renal Disease

Cited by 543 publications

References 41 publications

Bone–Vascular Axis in Chronic Kidney Disease

Bone–Vascular Axis in Chronic Kidney Disease

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

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