Comparison of the Effects of Denosumab and Alendronate on Cardiovascular and Renal Outcomes in Osteoporotic Patients

Hsu, Tsuen-Wei; Hsu, Chien‐Ning; Wang, Shih‐Wei; Huang, Chiang-Chi; Li, Lung-Chih

doi:10.3390/jcm8070932

Cited by 11 publications

(15 citation statements)

References 45 publications

(56 reference statements)

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“…As a higher rate of eGFR decline was observed in the denosumab group, this may translate to the possible worsening of CKD progression in denosumab users. This finding was consistent with a previous study comparing denosumab with alendronate, and the increase in renal function decline in the denosumab group was also observed in patients with poor baseline renal function with an eGFR of <60 mL/min/1.73 m 2 (aHR, 1.5; 95% CI 1.09-2.07; p = 0.0132) [18]. However, these results were in contrast to those of another FREEDOM extension study, which revealed no significant change in CKD stage between denosumab and placebo use [16].…”

Section: Discussionsupporting

confidence: 92%

“…Briefly, the CGRD contains individual patient-level EHR from the CGMH, providing 10–12% of health services reimbursed by Taiwan National Health Insurance (NHI) program in 2018 [ 19 ]. The data generalizability of CGRD has been validated in some disease populations [ 20 , 21 ], and the laboratory results have been used in kidney [ 18 , 22 , 23 ] and heart studies [ 24 ]. The CGRD data from January 2003 to December 2018 were used for the analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Along with bisphosphonates, both denosumab and raloxifene are recommended treatment agents in guidelines and are reimbursed by the Taiwan National Health Insurance program [ 17 ]; however, their long-term effects on renal function have not been studied in as much depth. In our previous study comparing the effects of denosumab and alendronate on cardiovascular and renal outcomes, an increased risk of deterioration in renal function in patients with renal insufficiency was observed in the denosumab group after 5-year follow-up [ 18 ]. Hence, this study aimed to further evaluate the various kidney outcomes of denosumab and raloxifene users in women with osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Adverse Kidney Outcomes in Women Receiving Raloxifene and Denosumab in a Real-World Setting

et al. 2022

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Both osteoporosis and kidney diseases are common and intercorrelate to increase morbidity and mortality in elderly women. This study aimed to compare adverse kidney outcome between women initiated with denosumab and a matched group of raloxifene initiators using propensity score matching methods in a large healthcare delivery system in Taiwan. The risks of adverse kidney outcomes were estimated using Cox proportional hazard regression and the change in kidney function over time was analyzed using the linear mixed model. A total of 9444 (4722 in each group) women were identified who matched the inclusion criteria between January, 2003 and December, 2018. Denosumab use was significantly associated with higher risk of eGFR decline ≥ 30% from baseline than raloxifene use (aHR: 1.26; 95% CI: 1.16–1.36, p < 0.0001). The mean change in eGFR over time was 1.24 mL/min/1.73 m2 per year in the denosumab group and 0.45 mL/min/1.73 m2 per year in the raloxifene group (p = 0.0004). However, the risks of acute kidney injury (10.53%) and chronic dialysis (0.66%) in this study cohort were not significantly different for the two anti-osteoporosis treatments. Close monitoring of the residual kidney function and treatment effect is needed in those with denosumab.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Adverse Kidney Outcomes in Women Receiving Raloxifene and Denosumab in a Real-World Setting

et al. 2022

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“…The calcified area apparently diminished through 30 months of treatment and it was deemed necessary for ≥2 years for decalcification due to denosumab. Hsu et al [ 18 ] demonstrated that denosumab use is associated with a significant reduction in cardiovascular events compared to alendronate use with better adherence of >60% medication possession ratio. Despite no significant differences in MI and heart failure between the denosumab and raloxifene groups, our study did not obtain evidence of vascular calcification in X-ray or CT, owing to data limitations.…”

Section: Discussionmentioning

confidence: 99%

“…Denosumab has been shown to exert protective effects against CVD [ 18 ]. Chen et al [ 19 ] reported that denosumab suppress the progression of coronary arterial calcification.…”

Section: Introductionmentioning

confidence: 99%

Denosumab Is Superior to Raloxifene in Lowering Risks of Mortality and Ischemic Stroke in Osteoporotic Women

et al. 2023

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Both osteoporosis and cardiovascular disease (CVD) share similar pathways in pathophysiology and are intercorrelated with increased morbidity and mortality in elderly women. Although denosumab and raloxifene are the current guideline-based pharmacological treatments, their impacts on cardiovascular protection are yet to be examined. This study aimed to compare mortality rate and cardiovascular events between denosumab and raloxifene in osteoporotic women. Risks of CVD development and all-cause mortality were estimated using Cox proportional hazard regression. A total of 7972 (3986 in each group) women were recruited between January 2003 and December 2018. No significant difference between denosumab and raloxifene was observed in composite CVDs, myocardial infarction, or congestive heart failure. However, comparison of the propensity score matched cohorts revealed that patients with proportion of days covered (PDC) ≥60% had lower incidence of ischemic stroke in the denosumab group than that in the raloxifene group (aHR 0.68; 95% CI 0.47–0.98; p = 0.0399). In addition, all-cause mortality was lower in the denosumab group than in the raloxifene group (aHR 0.59; 95% CI 0.48–0.72; p = 0.001), except in patients aged <65 y/o in this cohort study. We concluded that denosumab is superior to raloxifene in lowering risks of all-cause mortality and certain ischemic strokes in osteoporotic women.

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Cardiovascular Safety in Postmenopausal Women and Men With Osteoporosis Treated With Denosumab and Zoledronic Acid: A Post‐Authorization Safety Study

Spangler,

Nielson,

Brookhart

et al. 2023

JBMR Plus

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Osteoporosis and cardiovascular disease are common in older adults. Treatment of osteoporosis reduces the burden of debilitating fractures; however, it is important to understand the benefit versus risk of treatment. This study evaluates the risk of stroke (ischemic or hemorrhagic) and myocardial infarction (MI) among postmenopausal women and men initiating osteoporosis treatment with denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor) or zoledronic acid (bisphosphonate) between October 2010 and June 2019. A retrospective cohort study employing the new user/active comparator design was conducted. Analyses were conducted separately in two national US commercial databases, MarketScan® and Optum® for reproducibility. Inverse probability of treatment and censoring weighting was employed to control for confounding and informative censoring. Cumulative risks at 6‐month, 12‐month, and 36‐month time points were calculated and adjusted risk ratios and differences (with 95% confidence intervals [CIs]) were estimated. In MarketScan® and Optum® databases, 96,611 and 73,127 patients met all study eligibility criteria, respectively. At 36 months, the risk ratio estimates (zoledronic acid referent group) were 1.22 (95% CI, 0.77–1.66) and 0.97 (95% CI, 0.63–1.32) for MI and 1.00 (95% CI, 0.61–1.40) and 0.87 (95% CI, 0.56–1.17) for stroke in MarketScan and Optum, respectively. Most of the treatment associations across the other time periods and outcomes also had 95% CIs including the null value. In these large samples of real‐world US patients, no increased risk in MI and stroke were identified for up to 36 months of treatment in denosumab users compared with zoledronic acid users. © 2023 Amgen. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Comparison of the Effects of Denosumab and Alendronate on Cardiovascular and Renal Outcomes in Osteoporotic Patients

Cited by 11 publications

References 45 publications

Comparative Adverse Kidney Outcomes in Women Receiving Raloxifene and Denosumab in a Real-World Setting

Comparative Adverse Kidney Outcomes in Women Receiving Raloxifene and Denosumab in a Real-World Setting

Denosumab Is Superior to Raloxifene in Lowering Risks of Mortality and Ischemic Stroke in Osteoporotic Women

Cardiovascular Safety in Postmenopausal Women and Men With Osteoporosis Treated With Denosumab and Zoledronic Acid: A Post‐Authorization Safety Study

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