Kidney Function Change and All-Cause Mortality in Denosumab Users with and without Chronic Kidney Disease.

Ping-Hsun Wu,Mei-Chuan Kuo,Tien-Ching Lee,Jer-Ming Chang,Chung-Hwan Chen,Sung-Yen Lin,Ming-Yen Lin,Yi-Wen Chiu,Shang-Jyh Hwang,Teng-Hui Huang

doi:10.3390/jpm12020185

Abstract

Denosumab is approved for osteoporosis treatment in subjects with and without chronic kidney disease (CKD). Confirmation is required for its safety, treatment adherence, renal function effect, and mortality in patients with CKD. A retrospective cohort study was conducted to compare new users of denosumab in terms of their two-year drug adherence in all participants (overall cohort) and CKD participants (CKD subcohort), which was defined as baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. We defined high adherence (HA) users as receiving three or four doses and low adherence (LA) users as receiving one or two doses. All-cause mortality was analyzed using Kaplan–Meier curves and Cox regression models. In total, there were 1142 subjects in the overall cohort and 500 subjects in the CKD subcohort. HA users had better renal function status at baseline than LD users in the overall cohort. A decline in renal function was only observed among LD users in the overall cohort. In the CKD subcohort, no baseline renal function difference or renal function decline was demonstrated. The all-cause mortality rate of HA users was lower than LA users in both the overall cohort and CKD. A randomized control trial is warranted to target this unique population to confirm our observations.

Highlights

We excluded patients with incomplete demographic data or who were receiving dialysis treatment, taking other osteoporosis drugs, had a malignancy diagnosis with denosumab treatment, or who died within two years after the index date
Comparisons of the baseline characteristics between high adherence (HA) and low adherence (LA) denosumab users were performed within the overall cohort and the chronic kidney disease (CKD) subcohort
There were no differences in age, gender, overall fracture history, Charlson comorbidity index (CCI) score, or concurrent medication between the two groups in either the overall cohort or the CKD subcohort

Summary

Introduction

Chronic kidney disease (CKD) is commonly associated with mineral and bone disorders, osteoporosis, and an increased risk of fractures [1,2,3,4,5]. The World Health Organization defines osteoporosis as being diagnosed with a T-score of ≤−2.5. CKD is an independent risk factor for osteoporosis [6] and fragility fractures, especially hip fractures, are associated with high complications and mortality rates [7,8,9]. Eighty-five percent of women with osteoporosis have mild-to-moderate renal impairment [10]. Since osteoporosis and CKD have a strong association, it is important to treat osteoporotic patients with renal insufficiency effectively and safely, without causing any adverse effects on intrinsic renal function [5]

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Results

Conclusion