Once-yearly zoledronic acid and change in abdominal aortic calcification over 3 years in postmenopausal women with osteoporosis: results from the HORIZON Pivotal Fracture Trial

Cai, Guoqi; Keen, Helen; Host, Lauren V; Aitken, Dawn; Laslett, Laura L; Winzenberg, Tania; Wluka, Anita E.; Black, Dennis M.; Jones, Graeme

doi:10.1007/s00198-020-05430-z

Cited by 14 publications

(16 citation statements)

References 43 publications

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“…FGF21 analogues also increased blood markers of bone loss in 2 of the human studies [29, 30]. Many studies have demonstrated an independent association between osteoporosis and VC [31, 32]. The role of FGF21 in VC has rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

Jiang

Yin

et al. 2021

Kidney Dis

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Background: Cardiovascular disease (CVD) is the leading cause of death in haemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and is strongly associated with CVD events and mortality in HD patients. VC coexists with osteoporosis in many studies. Fibroblast growth factor 21 (FGF21) which is known as an adipocytokine is a new hypoglycemic strategy and is inversely related to bone mineral density. Methods: To evaluate the contribution of FGF21 to VC in HD patients, we detected circulating FGF21 levels and measured the whole thoracic aorta calcification scores (TACS) and calcification scores of the 3 segments of thoracic aorta, including ascending thoracic aorta (ATACS), aortic arch (AoACS), and descending thoracic aorta (DTACS) of our HD patients in this cross-sectional study. In addition, we pre-incubated human aortic endothelial cells (HAECs) with FGF21 in the presence or absence of parathyroid hormone (PTH) in vitro. Results: The median serum FGF21 level in HD patients was 11-fold higher than that in healthy controls. Ln(FGF21) was positively correlated with Ln(TACS+1), Ln(ATACS+1), Ln(AoACS+1), and Ln(DTACS+1), respectively, in HD patients. Serum FGF21 was independently associated with TACS and ATACS, AoACS, and DTACS. FGF21 which was combined with age, calcium, and intact PTH demonstrated a high area under the curve of 0.84 with optimal sensitivity (84%) and specificity (71%) for the prediction of VC in HD patients. Our vitro results showed that FGF21 enhanced the calcification effect of PTH on HAECs by increasing calcium deposition and endothelial-to-mesenchymal transition. Conclusions: Circulating FGF21 was notably higher and was a potential predictor and promoter of VC in HD patients.

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Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

Jiang

Yin

et al. 2021

Kidney Dis

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“…AAC progression (defined as a change in semiquantitative AAC score) was similar between treatment groups (67/234 [28.6%] in zoledronic acid–treated versus 82/268 [30.6%] in placebo‐treated; odds ratio [OR] = 0.90; 95% CI, 0.6 to 1.3). ( 48 ) This did not differ by baseline AAC score, nor did change in total hip ( r = −0.02, p = 0.66) or femoral neck BMD ( r = 0.03, p = 0.54) correlate with AAC change. This overall suggests against a link between the skeleton and calcification in the vasculature as a potential mechanism explaining CV benefits or harms of BPs.…”

Section: What Is “Accepted” To Be Known?mentioning

confidence: 71%

“…Furthermore, there is need to better understand the clinical and biological links between skeletal and CV disease because antifracture medications appear to have no effect on aortic calcification (a robust marker of both skeletal and CV risks). ( 48,58 ) Therefore, exploring other mechanisms such as potential electrophysical effects, antithrombotic effects, effects on autonomic function after iv infusion, or plaque stabilization effects may offer a window into the bone‐vascular axis. In conclusion, the clinical message should be that osteoporosis medications have a very good safety record and that there is a clear research need to study the potential CV benefits that may, perhaps surprisingly, accompany restoration of bone health.…”

Section: Conclusion and Research Agendamentioning

confidence: 99%

Cardiovascular Safety of Antifracture Medications in Patients With Osteoporosis: A Narrative Review of Evidence From Randomized Studies

Rodríguez

Abrahamsen

2021

JBMR Plus

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Osteoporosis and cardiovascular (CV) disease share common risk factors and pathophysiology. Low bone mineral density (BMD) and fractures appear to increase the risk for multiple CV diseases. Equally, prevalent CV disease appears to predispose to bone loss and increase fracture rates. This relationship has naturally provoked the hypothesis that stopping bone loss may result in some CV benefit. Secondary analyses of safety and adverse event data from many randomized controlled trials (RCTs) have attempted to clarify this putative association. Recently, the discontinuation of odanacatib (anti‐cathepsin K monoclonal antibody) over stroke concerns and the imbalance in ischemic events in romosozumab‐treated (anti‐sclerostin monoclonal antibody) women compared to bisphosphonate‐treated women, has provided further justification to better characterize potential CV benefits and harms of osteoporosis medications. This review delves into the seminal, and other major RCTs of osteoporosis medications and, using both published data and additional information provided on trial registration pages, examines the evidence for CV safety and harms of these medications. Accepted and emerging “off‐target” effects are explored for validity, biological plausibility, and clinical importance. A brief research agenda is provided to stimulate the next wave of clinical development and CV understanding of osteoporosis medications. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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“…Cardiovascular disease as highly caused by vascular calcification and metabolic problems has been considered the primary cause of death in patients with renal disease [ 34 ]. Previous studies have demonstrated that bisphosphonates might inhibit or reduce vascular calcification in dialysis patients [ 35 – 37 ], although a recent post-hoc analysis of the HORIZON Pivotal Fracture Trial failed to support the hypothesis that zoledronic acid could affect the formation or progression of vascular calcification in postmenopausal women with osteoporosis [ 38 ]. This discrepancy might reflect drug actions of different classes of bisphosphonates, where nitrogen-containing bisphosphonates for example have much stronger AR potency without inhibiting bone mineralization than non-nitrogen-containing ones, and might have indirect effects on vascular calcification through influencing serum levels of calcium, phosphate, and parathyroid hormone.…”

Section: Discussionmentioning

confidence: 99%

“…progression of vascular calcification in postmenopausal women with osteoporosis [38]. This discrepancy might reflect drug actions of different classes of bisphosphonates, where nitrogencontaining bisphosphonates for example have much stronger AR potency without inhibiting bone mineralization than non-nitrogen-containing ones, and might have indirect effects on vascular calcification through influencing serum levels of calcium, phosphate, and parathyroid hormone.…”

Section: Plos Onementioning

confidence: 99%

Effectiveness of antiresorptive medications in women on long-term dialysis after hip fracture: A population-based cohort study

et al. 2020

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There is no clear evidence how effective the antiresorptive (AR) drugs alendronate and raloxifene are at reducing risk of second hip fracture and mortality in dialysis populations. The purpose of this study was to compare the risk of hospitalization for second hip fracture and risk of mortality between AR user and non-user groups in Taiwanese women on long-term dialysis with hip fractures. We conducted a retrospective cohort study using Taiwan National Health Insurance Research Datasets. Long-term dialysis women older than 50 years with newly diagnosed hip fractures and new to AR therapy from 2005 to 2011 were recruited. The patients were divided into AR users and non-users and matched by propensity score. We used Cox Proportional Hazards models to assess association of AR with risks of second hip fracture and mortality. Totally, 1,079 dialysis patients were included, and after matching, we were left with 74 AR users and 74 non-users. AR users did not show a significant reduction in the incidence of second hip fracture compared with non-users (adjusted Hazard Ratio (HR): 0.91, 95% CI: 0.30-2.76), and alendronate users exhibited higher risk of second hip fracture compared with raloxifene users (adjusted HR: 2.80, 95% CI: 0.42-18.79). In addition, AR users were found to have significantly lower 1-and 2-year mortality rates than the non-users (1-year: adjusted HR 0.25, 95% CI, 0.07-0.90; 2-year: 0.35, 95%CI: 0.17-0.72). AR treatment did not significantly improve the risk of second hip fracture but significantly reduce mortality in older women on dialysis. Further clinical trials on effectiveness of AR medications for dialysis populations should be warranted.

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Once-yearly zoledronic acid and change in abdominal aortic calcification over 3 years in postmenopausal women with osteoporosis: results from the HORIZON Pivotal Fracture Trial

Cited by 14 publications

References 43 publications

Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

Cardiovascular Safety of Antifracture Medications in Patients With Osteoporosis: A Narrative Review of Evidence From Randomized Studies

Effectiveness of antiresorptive medications in women on long-term dialysis after hip fracture: A population-based cohort study

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