Risedronate therapy in patients with mild-to-moderate chronic kidney disease with osteoporosis: post-hoc analysis of data from the risedronate phase III clinical trials

Abstract

BackgroundThe clinical effect of bisphosphonate treatment has not been clearly evaluated by kidney function in Japanese Chronic Kidney Disease (CKD) patients with osteoporosis. This study analyzed the data from three risedronate Japanese phase III trials. The clinical effect of risedronate therapy was evaluated in CKD patients with osteoporosis.MethodsThe Japanese clinical trials involved 852 subjects who received risedronate (2.5 mg once daily or 17.5 mg once weekly) and whose estimated glomerular filtration rate (eGFR) were calculable and at ≥ 30 mL/min. The subjects were divided into subgroups according to the eGFR level: ≥ 90 mL/min/1.73 m2, ≥ 60 to < 90 mL/min/1.73 m2, ≥ 30 to < 60 mL/min/1.73 m2. Lumbar spine bone mineral density (BMD), bone turnover markers (BTMs) and adverse events were evaluated at 48 weeks.ResultsAdverse event incidence was similar among three subgroups. There was also no exacerbation of impaired kidney function associated with risedronate administration in the subjects with eGFR above 30 mL/min/1.73 m2. Risedronate administration induced a significant increase in lumbar spine BMD and significant inhibition of BTMs in three subgroups.ConclusionsThe risedronate therapy showed similar clinical effects in CKD patients with osteoporosis compared to those without CKD.

Management of Osteoporosis in CKD

“…A significant improvement in lumbar spine BMD (P,0.001) and a significant suppression in the bone turnover markers urine N-terminal telopeptide of type 1 collagen, urine C-terminal telopeptide of type 1 collagen, and bone alkaline phosphatase (P,0.001) were observed. The increase in lumbar spine BMD did not differ between subjects with eGFR$30 to ,60, $60 to ,90, and $90 ml/min per 1.73 m 2 (28). Treatment with alendronate similarly increased BMD at the spine and hip and reduced the risk of clinical and spine fractures in subjects with and without an eGFR,45 ml/min.…”

“…In a secondary analysis of the Fracture Intervention Trial, 9.9% of the subjects were found to have an eGFR,45 ml/min (27). More recently, Shigematsu et al (28) performed a post hoc analysis of pooled data from three Japanese clinical trials on 852 subjects with osteoporosis who were administered risendronate. The eGFRs of the subjects ranged from 30 to $90 ml/min per 1.73 m 2 .…”

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review

“…In patients with CKD G1–4, a retrospective analysis that pooled nine clinical trials showed that risedronate increased BMD and prevented vertebral fractures regardless of degree of renal impairment [ 122 ]. In patients with CKD G1–3, a post hoc analysis of three Japanese trials concluded that risedronate could increase lumbar spine BMD without differences in CKD stage 1-3 [ 123 ]. In a secondary analysis of the Fracture Intervention Trial (FIT), administration of alendronate was safe and effective in increasing total hip and BMD and reducing spinal fractures in women with eGFR <45 mL/min [ 124 ].…”

Rethinking Bone Disease in Kidney Disease

“…Given the heterogeneity of the studies included, the use of bisphosphonates was associated with a nonsignificant reduction in fracture risk and moderate evidence that bisphosphonates may reduce loss of lumbar spine BMD but not femoral neck BMD. A recent post hoc analysis of three Japanese RCTs compared risedronate to placebo in 852 patients with an eGFR from 30 to >90 mL/min (with 228 having an eGFR <60) . Patients were analyzed according to eGFR level ≥90, 60 to <90, and ≥30 to <60 mL/min/1.73 m 2 , and lumbar BMD, BTMs (CTX, P1NP, and BSAP) were evaluated at 48 weeks.…”