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

Abstract

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.

Insights and implications of sexual dimorphism in osteoporosis

“…Various studies have indicated the adverse effects of the long-term use of SREMs. 394 , 395 SREMs have been reported to be associated with uterine cancer, venous thromboembolism, and fatal strokes, which remain a major concern for long-term therapy for osteoporosis. 396 …”

Monoclonal antibodies in patients with osteoporosis and renal insufficiency: An updated systematic review and meta-analysis

“…RoB 2 identified two studies at some concerns of bias due to deviations from intended interventions and selection of the reported results [ 17 , 18 ] ( Table S1 ). ROBINS-I identified three studies at moderate risk of bias, due to confounding adjustment and selection of reported results [ 15 , 16 , 19 ] ( Table S2 ).…”

“…On eGFR change, there was no statistical difference between the groups, with a comparable result between MAb and control groups. However, it should be carefully interpreted, since Chen 2022 [ 15 ] indicated a higher rate of eGFR decline in the denosumab group, and Hsu 2019 [ 16 ] found denosumab treatment to be associated with a significantly higher risk of eGFR ≥ 30%. Thus, it is encouraged to eGFR be complemented with objective findings such as quantification of urinary albumin to improve kidney function assessment and optimally predict worsening renal function [ 26 ].…”

Clinical Characteristics, Outcomes, and Prognosis among Cancer Patients with Acute Kidney Injury: A Single-Center Study at Sohag Cancer Center

“…Doxorubicin, an antitumor antibiotic, is also linked to TMA, nephrotic syndrome, focal segmental glomerular sclerosis, and AKI among cancer patients [16] . Although few studies have examined the association between denosumab and the occurrence of AKI, initial reports suggest an increased risk of AKI among patients receiving this drug [17] .…”