Purpose: Osteoporosis and renal insufficiency are coexisting disease states in a substantial proportion of postmenopausal women. Since bisphosphonates are generally contraindicated in patients (pts) with estimated GFR (eGFR) < 35 mL/min, it is important to evaluate other osteoporosis treatments in this setting. This post hoc analysis of the FRAME study assessed the efficacy and safety of romosozumab (Romo) vs placebo (Pbo) among pts with different levels of renal function.
Methods: FRAME enrolled 7,180 postmenopausal women with T-scores –2.5 to –3.5 at the total hip (TH) or femoral neck (FN). In the Pbo-controlled double-blind treatment phase, pts received Romo 210 mg or Pbo monthly for 12 months. Pts were grouped by baseline eGFR (mL/min/1.73m2) normalized to body surface area, calculated using the MDRD study equation. Renal function was categorized as normal renal function (eGFR ≥ 90) or mild (eGFR 60–89 [CKD stage 2]), moderate (eGFR 30–59 [CKD stage 3]), or severe (eGFR 15–29 [CKD stage 4]) renal insufficiency. The least squares mean (LSM) % change from baseline in bone mineral density (BMD) at the lumbar spine (LS), TH, and FN; incidence of new vertebral fractures (VFx) and AEs; and CKD progression were assessed for each eGFR category at month 12.
Results: At baseline, most pts (88%) had mild or moderate renal insufficiency; 0.3% had severe renal insufficiency. In the overall pt population, the LSM % change (95% CI) from baseline in BMD (Romo vs Pbo) was 13.1% (12.8–13.3) vs 0.4% (0.2–0.5) for LS, 6.0% (5.9–6.2) vs 0.3% (0.1–0.4) for TH, and 5.5% (5.2–5.7) vs 0.3% (0.1–0.5) for FN. Changes in BMD were similar irrespective of baseline eGFR (Figure). Incidence of new VFx (Romo/Pbo) in pts with normal renal function, CKD 2, or CKD 3 was 0.5%/3.0%, 0.4%/1.5%, and 0.6%/2.1%, respectively. The overall incidence of AEs and SAEs and the incidence of positively adjudicated cardiovascular events were similar between treatment groups for all eGFR categories. One pt (CKD 2 at baseline) in the Romo group had grade 2 hypocalcemia. Mild-to-moderate calcium decrease occurred in 4 pts in the Pbo group and 13 pts in the Romo group. Most pts (approximately 80% in each group) had no changes from baseline eGFR category at the end of the 12-month period.
Conclusions: Romo increased BMD across eGFR subgroups vs Pbo, and the reduction in new VFx was not notably affected by eGFR level. Safety was also generally comparable among eGFR subgroups.