Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study

Barreto, Daniela Veit; Barreto, Fellype de Carvalho; Carvalho, Aluízio Barbosa de; Cuppari, Lílian; Draibe, Sérgio Antônio; Dalboni, Maria Aparecida; Moysés, Rosa Maria Affonso; Neves, Kátia R.; Jorgetti, Vanda; Miname, Márcio H.; Santos, Raul D.; Canziani, María Eugênia Fernandes

doi:10.1053/j.ajkd.2008.06.024

Cited by 117 publications

(90 citation statements)

References 40 publications

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“…Thus, the difference between the CARE-2 study and the TTG and RIND studies was not that the calcium binder had no harm; rather, it was that sevelamer showed no benefit in CARE-2. Finally, in the Phosphate Binder Impact on Bone Remodeling and Coronary Calcification (BRIC) study, calcium binders were more likely to lead to low-turnover disease seen on bone biopsy than was sevelamer, and low-turnover bone disease was more likely to be associated with increased coronary artery calcification (60,68).…”

Section: Potential Adverse Effects Of Calcium Supplements and Bindersmentioning

confidence: 99%

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

Jamal

Moe

2012

Clinical Journal of the American Society of Nephrology

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SummaryCalcium supplementation has been considered the gold standard therapy for osteoporosis in the general population. It is given in both the placebo and treatment groups of trials evaluating antifracture efficacy of new therapies. Similarly, calcium-based phosphate binders have been considered the gold standard comparator for all new phosphate binders. However, large randomized trials demonstrate conflicting data on the antifracture efficacy of calcium supplementation, particularly in high doses, in patients with osteoporosis without CKD. In addition, recent data suggest an increased risk for cardiovascular events. These new studies raise safety concerns for the general approach with calcium supplementation and binders. This review describes recent data on the adverse effects of calcium supplementation for osteoporosis and how these new data should affect the strategy for phosphate binder use in CKD.

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Section: Potential Adverse Effects Of Calcium Supplements and Bindersmentioning

confidence: 99%

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

Jamal

Moe

2012

Clinical Journal of the American Society of Nephrology

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“…(24)(25)(26) Clinical improvements in bone health, regardless of the initial bone defect, ameliorate progression of cardiovascular disease. (23) Taken together, these observations support a mechanistic link between bone health and cardiovascular disease and have prompted the Kidney Disease: Improving Global Outcomes (KDIGO) organization to describe characteristics in mineral dysregulation as CKD-mineral bone disorder (CKD-MBD). (27) Hence, CKD-MBD is associated with characteristic laboratory findings, progressive alterations in bone remodeling, and soft-tissue calcification.…”

Section: Introductionmentioning

confidence: 97%

“…(15) Agents that enhance bone quality also reduce cardiovascular calcification. (16)(17)(18)(19)(20)(21)(22)(23) Additionally, soft-tissue calcification including vascular calcification is a common feature of genetic mouse and rat models harboring defects associated with bone mineralization. (24)(25)(26) Clinical improvements in bone health, regardless of the initial bone defect, ameliorate progression of cardiovascular disease.…”

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

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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%

“…Although low-turnover bone disease is frequent among nondialyzed CKD patients (16,17), it remains unclear whether loss of bone mass is mandatory in the course of low-turnover bone disease. In a study with hemodialysis patients, Barreto et al (35) showed that lower trabecular bone volume was associated with the development of CAC, and the improvement of bone turnover was associated with lower CAC progression. These data provide evidence that disturbances in bone metabolism may lead to vascular calcification.…”

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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Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study

Cited by 117 publications

References 40 publications

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

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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