Romosozumab versus Placebo: A Comparison in Varying Levels of Kidney Disease

A post-hoc analysis of the FRAME study analyzed safety and efficacy outcomes of romosozumab compared with placebo among postmenopausal women with mild-to-moderate kidney disease. The results of the study were presented at the ACR/ARP Annual Meeting.

“Osteoporosis and renal insufficiency are coexisting disease states in a substantial proportion of postmenopausal women,” said study author Johnathan Adachi, MD, BSc, FRCP, of the McMaster University and St. Joseph’s Healthcare Hamilton in Canada, who presented the study’s findings. “Prescribing information for bisphosphonates warns against using these agents for patients with [estimated glomerular filtration rate (eGFR)] of less than 30 or 35 mL/min; therefore, it is important to evaluate other osteoporosis treatments in this setting.”

The FRAME study included 7,180 postmenopausal women whose T-scores at the total hip or femoral neck ranged from –2.5 to –3.5. Patients received either romosozumab 210 mg or placebo monthly for one year. The women were stratified by baseline eGFR normalized to body surface area. Renal function was defined as normal (eGFR ≥90), mild (eGFR 60 to 89 [chronic kidney disease (CKD) stage 2]), moderate (eGFR 30 to 59 [CKD stage 3]), or severe (eGFR 15 to 29 [CKD stage 4]). One-year assessments were conducted to determine the least squares mean percent change in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck; new vertebral fractures; adverse events (AEs); and CKD progression.

Baseline renal insufficiency was mild to moderate in most patients (88%) and severe in 0.3% of patients. The least squares mean percent change from baseline in BMD in the entire cohort at the lumbar spine was 13.1% in the romosozumab group compared with 0.4% for placebo; for total hip, 6.0% versus 0.3%, respectively; and for femoral neck, 5.5% versus 0.3%, respectively.

Regardless of baseline eGFR, patients presented similar changes in BMD. Across CKD levels, romosozumab patients had a lower incidence of new vertebral fractures compared with placebo (normal renal function, 0.5% vs 3.0%; CKD 2, 0.4% vs 1.5%; and CKD 3, 0.6% vs 2.1%). Across eGFR groups, the rates of AEs, serious AEs, and positively adjudicated cardiovascular events were similar between treatment groups. One incidence of grade 2 hypocalcemia was recorded in a patient with CKD 2 at baseline. Mild-to-moderate calcium decrease was more common among patients receiving romosozumab (n=13) than placebo (n=4). Across groups, the majority of patients presented no one-year changes in eGFR category.

“There were large gains in BMD [achieved] with romosozumab compared with placebo, irrespective of renal function level. The risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level. The safety of romosozumab was generally comparable among eGFR subgroups. And romosozumab could be considered a treatment option for osteoporotic patients with mild-to-moderate CKD,” concluded Dr. Adachi.