Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: A Retrospective Cohort Study

Hartle, James E.; Tang, Xiaoqin; Kirchner, H. Lester; Bucaloiu, Ion D.; Sartorius, Jennifer; Pogrebnaya, Zhanna V.; Akers, G.; Carnero, Guillermo; Perkins, Robert M.

doi:10.1053/j.ajkd.2011.11.037

Cited by 36 publications

(21 citation statements)

References 21 publications

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“…Animal models show clearly that bisphosphonates accumulate and show activity in calcified arterial vessels; whether this result, in turn, increases risk is not clear (24,25). In a previous study, we reported a modest protective association of bisphosphonates in a similar study population without a prior history of a major cardiovascular event but with a different study enrollment period, inclusion criteria, and follow-up period (10). In the analysis presented here, the derivation of the study population across the sensitivity analyses had a considerable impact on risk associations; in three of four approaches, the protective association was again observed among those patients without cardiovascular disease, although this association was statistically significant in only the analysis adjusting for treatment indication (approach 4).…”

Section: Discussionmentioning

confidence: 84%

“…We have previously reported that, among adult patients with CKD and without clinically manifest cardiovascular disease, bisphosphonate therapy is associated with a lower risk of death (10). Of some concern in subgroup analyses was that this association was lost among those patients with coronary disease or cardiac dysrhythmia, suggesting the possibility that the presence of cardiovascular disease may modify any protective mortality benefit among those patients with CKD treated with a bisphosphonate.…”

Section: Introductionmentioning

confidence: 99%

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Bisphosphonates and Mortality in Women with CKD and the Presence or Absence of Cardiovascular Disease

Perkins

Kirchner

Matsushita

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives A modest protective association between bisphosphonate prescription and mortality among women with CKD but without clinically manifest cardiovascular disease has been shown. Whether a prior cardiovascular event (myocardial infarction, stroke, or heart failure) modifies this association is unknown.Design, setting, participants, & measurements A cohort of adult women with stages 3 and 4 CKD receiving primary care in a rural integrated health care system during the period 2004-2011 without history of advanced malignancy or organ transplantation (n=6756, median age=74 years, median follow-up=4.3 years) was retrospectively assembled. The primary analysis compared those patients prescribed bisphosphonates (both prevalent and incident use during follow-up) with those patients not prescribed. Additional approaches were taken to account for survival and indication biases. The primary outcome was time to death by Cox multivariable regression.Results In the primary analysis, compared with women not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was history of cardiovascular event (P for interaction=0.004). In the additional approaches, associations between bisphosphonate prescription and mortality among those patients with a prior cardiovascular history varied: hazard ratios (95% confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94 (0.66 to 1.34). Interaction by prior cardiovascular event history varied across these three approaches (P=0.07, P=0.22, and P=0.05). ConclusionIn this study of women with CKD, the association between bisphosphonate treatment and mortality risk was inconclusive across a series of analyses designed to account for various types of selection and indication bias.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Bisphosphonates and Mortality in Women with CKD and the Presence or Absence of Cardiovascular Disease

Perkins

Kirchner

Matsushita

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Over a median followup period of 3.9 years, Cox regression analysis showed that bisphosphonates therapy was not correlated with reduced risk of composite endpoint of MI, heart failure, or stroke. 27 The neutral results of present meta-analysis could be interpreted as follows. First, experimental studies investigating the effect of bisphosphonates on atherosclerosis, which presented intriguing results, were mainly performed in male animals, whereas human studies often included significantly more women than men.…”

Section: Discussionmentioning

confidence: 94%

Association Between Bisphosphonates Therapy and Incident Myocardial Infarction

Huang

Gui

et al. 2015

Journal of Cardiovascular Pharmacology

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“…In the multiethnic study of atherosclerosis, bisphosphonates reduce vascular calcification in older women but increased calcification in younger ones [34]. A retrospective cohort study of female patients with CKD stages 3–4 revealed that bisphosphonates therapy was not associated with lower risk of cardiovascular events although it was associated with diminished risk of all-cause mortality [98]. In addition, ibandronate did not improve aortic calcification in osteoporotic elderly women [99], and alendronate did not decrease the progression of vascular calcification in patients with CKD stages 3–4 [100].…”

Section: Therapeutic Approaches To Vascular Calcification In Ckdmentioning

confidence: 99%

Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature

Byon

Chen

2015

Curr Osteoporos Rep

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Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and increases mortality in those patients. Impaired calcium and phosphate homeostasis, increased oxidative stress, and loss of calcification inhibitors have been linked to vascular calcification in CKD. Additionally, impaired bone may perturb serum calcium/phosphate and their key regulator, parathyroid hormone, thus contributing to increased vascular calcification in CKD. Therapeutic approaches for CKD, such as phosphate binders and bisphosphonates, have been shown to ameliorate bone loss as well as vascular calcification. The precise mechanisms responsible for vascular calcification in CKD and the contribution of bone metabolism to vascular calcification have not been elucidated. This review discusses the role of systemic uremic factors and impaired bone metabolism in the pathogenesis of vascular calcification in CKD. The regulation of the key osteogenic transcription factor Runt-related transcription factor 2 (Runx2) and the emerging role of Runx2-dependent receptor activator of nuclear factor kappa-B ligand (RANKL) in vascular calcification of CKD are emphasized.

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Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: A Retrospective Cohort Study

Cited by 36 publications

References 21 publications

Bisphosphonates and Mortality in Women with CKD and the Presence or Absence of Cardiovascular Disease

Bisphosphonates and Mortality in Women with CKD and the Presence or Absence of Cardiovascular Disease

Association Between Bisphosphonates Therapy and Incident Myocardial Infarction

Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature

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