Denosumab reduced incidences of fractures, and long-term exposure did not progress renal deterioration among women with mild to moderate chronic kidney disease (CKD). These findings, from an open-label extension of a phase 3, double-blind trial, were published in the Journal of Clinical Endocrinology and Metabolism.
At 214 centers worldwide, investigators recruited women aged 60 to 90 years with hip or spinal bone mineral densities (BMD) between −4 and −2.5. They randomly assigned patients to receive 60 mg of subcutaneous denosumab every 6 months or a placebo for 3 years. Patients in the treatment (n=2342) and placebo (n=2200) groups could enroll in a 10-year (long-term) or 7-year (crossover) open-label denosumab extension, respectively. Researchers assessed incidence of fractures and renal function.
Before receiving denosumab, 84% of the long-term and 81% of the crossover participants had CKD stage 2 or 3.
The rate of new vertebral fractures during the first 3 years was elevated among the placebo recipients and highest among persons without CKD (2.5% vs 0.6%), followed by patients with CKD stage 2 (1.7% vs 0.3%), CKD stage 3a (0.9% vs 1.2%), and CKD stage 3b (1.6% vs 0), respectively.
Incidence of vertebral fractures remained low among the long-term extension group (0.9%, 0.8%, 0.8%, 0.7%) and were higher among the crossover group (1.7%, 1,7%, 1,4%, 1,7%) among the patients without CKD and with CKD stage 2, CKD stage 3a, and CKD stage 3b, respectively.
Compared with baseline, after the long-term extension, BMD of the lumbar spine and hip increased by 22% and 9.7% among patients without CKD; 21.7% and 9.4% among patients with CKD stage 2; 21.7% and 9.8% among patients with CKD stage 3a; and 23.7% and 7.4% among patients with CKD stage 3b, respectively. After the crossover extension, researchers observed BMD increases of 17.1% and 8.2% among patients without CKD; 17% and 7.5% among patients with CKD stage 2; 16.8% and 7.6% among patients with CKD stage 3a; and 14.9% and 6.2% among patients with CKD stage 3b.
Renal function was unaffected by long-term (45.8%) and crossover (59.4%) exposure to denosumab among patients who began the study with normal renal function. Progression to CKD stage 2 was observed among 48.5% and 35.5%, respectively. Among the patients who had CKD at baseline, 63.9% of the long-term group and 65.9% of the crossover cohort maintained their CKD stage subgroup. No participants were given renal replacement therapy during the study.
Adverse event rates were similar between groups and most CKD stages; however, severe adverse events were elevated among patients with CKD stage 3b. For the long-term and crossover groups, investigators observed osteonecrosis of the jaw among 7 and 5 participants and hypocalcemia among 6 and 10 participants, respectively.
This study was limited by excluding patients who required dialysis. It remains unclear what effect denosumab would have in a dialysis treatment setting.
The study authors concluded long-term denosumab exposure was efficacious at reducing fractures and increasing BMD without causing a clinical alteration of renal function among postmenopausal women.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Broadwell A, Chines A, Ebeling PR, et al. Denosumab safety and efficacy among subjects in the FREEDOM extension study with mild-to-moderate chronic kidney disease [published online November 19, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa851