Romosozumab improves BMD, reduces fracture risk in women with osteoporosis and CKD
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Romosozumab improved bone mineral density at the lumbar spine, total hip and femoral neck, and reduced the relative risk for fractures in women with osteoporosis and mild-to-moderate chronic kidney disease, according to study data.
“There is an urgent need to effectively treat osteoporosis in patients with CKD, as patients with these combined comorbidities have more than double the risk for hip fracture than the general population, and mortality rates after fracture are three-fold higher for patients with CKD compared with age-matched individuals,” Paul D. Miller, MD, founder and director of Miller Bone Center at Colorado Center for Bone Health, and colleagues wrote in a study published in Journal of Bone and Mineral Research. “The evolving paradigm for osteoporosis treatment in the setting of CKD requires large-scale safety data from studies on emerging treatments for patients at different levels of CKD function. This post-hoc analysis demonstrated that, among patients with CKD stages 1 to 3, romosozumab 210 mg, administered subcutaneously once monthly for 12 months, is an effective treatment for osteoporosis compared with placebo or alendronate.”
Researchers conducted a post-hoc analysis of two phase 3 trials, the Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) and the Active-controlled Fracture Study in Postmenopausal Women with Osteoporosis at High risk (ARCH). In FRAME, participants were randomly assigned to 210 mg romosozumab (Evenity, Amgen) or placebo monthly for 1 year, whereas participants in ARCH were randomly assigned to 1 year of romosozumab or alendronate therapy. Participants were stratified by estimated glomerular filtration rate (eGFR), with an eGFR of 90 mL/min categorized as normal kidney function, an eGFR of 60 to 89 mL/min categorized as mild CKD and an eGFR of 30 to 59 mL/min defined as moderate CKD. Percent change in BMD from baseline to 1 year at the lumbar spine, total hip and femoral neck, and incidence of new vertebral fractures were analyzed for each eGFR group.
Of participants in FRAME, 69% had mild CKD and 19% had moderate CKD. The ARCH cohort included 61% with mild CKD and 24% with moderate CKD.
BMD improved in all kidney function groups
In both cohorts, significant BMD increases were observed across all three kidney function categories in the lumbar spine, total hip and femoral neck for participants taking romosozumab compared with placebo or alendronate. In FRAME, the BMD increases in the femoral neck were similar for participants with normal kidney function compared with those with mild or moderate reductions in kidney function, but there were slight differences in BMD increase in the lumbar spine (P for interaction < .001) and total hip (P for interaction = .003). In ARCH, the BMD increases between the groups were similar at the lumbar spine and femoral neck but varied slightly at the total hip (P for interaction = .013).
In FRAME, the relative risk for new vertebral fractures in women taking romosozumab at 1 year declined 84% in those with normal kidney function, 70% in women with mild CKD and 72% in those with moderate CKD. In ARCH, the risk for new vertebral fractures at 1 year declined 57% for women with normal kidney function taking romosozumab and 51% for those with moderate CKD taking romosozumab. No significant reduction was observed in the mild CKD group of ARCH.
No change in kidney function for most women
Treatment-emergent adverse events and serious adverse events were comparable in both cohorts and across all kidney function categories. The majority of participants in FRAME and ARCH remained in the same eGFR category from baseline to 1 year. Among those with normal kidney function at baseline, 30% to 42% had mild CKD at 1 year in both treatment groups of each trial.
“Romosozumab is an effective treatment for postmenopausal women with osteoporosis and mild-to-moderate reduction in kidney function,” the researchers wrote. “Romosozumab did not impact kidney function, nor was it associated with an increase in adverse events in this population. Additional studies are needed to assess efficacy in patients with a severe reduction of kidney function.”
Perspective
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Many patients in clinical practice have both osteoporosis and chronic kidney disease. Comorbid kidney failure causes a substantial increase in fracture risk compared to individuals with normal kidney function. Romosozumab is our newest pharmacologic osteoporosis therapy, administered at a dose of 210 mg subcutaneously monthly for 12 months, followed by an antiresorptive agent. Romosozumab acts to inhibit sclerostin and both increases bone formation and decreases bone resorption.
Miller and colleagues performed a post-hoc analysis of two trials of romosozumab, the pivotal Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) trial comparing romosozumab and placebo, and the Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH) comparing romosozumab to alendronate. In a subgroup analysis of individuals with mild to moderate chronic kidney failure, defined as an estimated glomerular filtration rate of 30 mL/min to 89 mL/min, they found that romosozumab was similarly efficacious in decreasing fracture risk in the subgroup of patients with kidney dysfunction, as well as equally safe. Romosozumab did not cause an increase in adverse effects, such as hypercalcemia, and did not result in worsening renal function in the subgroup studied.
Romosozumab is an important drug in our armamentarium against fracture, and this study increases the sense of security in prescribing romosozumab to our patients with both osteoporosis and renal disease.
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