Effects of Dapagliflozin on the Bone of Patients with CKD on Dialysis

Abstract

The effects of gliflozins on bones of CKD patients on dialysis are unknown. Recently, SGLT2 expression in bone tissue of patients with CKD has been reported. We hypothesized that dapagliflozin may act in bone cells and modulate the Klotho-FGF23 axis. This study analyzed the effects of dapagliflozin on serum bone biomarkers and related outcomes. In this predefined post-hoc analysis of a previous RCT, patients on dialysis received (1:1) dapagliflozin 10 mg daily or standard care for 24 weeks. The primary endpoint was the change from baseline in serum Klotho and FGF23 levels, compared by ranked analysis of covariance, adjusted by baseline. Exploratory analyses evaluated calcium, phosphate, PTH, bone-ALP, TRAP-5b, DKK1, sclerostin, and bone proteins. Bone fractures, osteopenia, and osteoporosis were outcomes of interest. Seventy-nine patients were included in this analysis (Control N=40 and Dapagliflozin N=39). At baseline, no significant differences in biomarkers were observed. The prevalence of osteopenia and osteoporosis was 73% and 43% (p = 0.60 and p = 1.00), respectively. After 24 weeks, the between-group analysis of the change from baseline (delta), adjusted by baseline, revealed a significant difference in serum Klotho [19.1 (- 38.9-86.3) pg/mL, Control group; - 29.1 (- 94.1-43.9) pg/mL, Dapagliflozin group (F:4.946, p = 0.03)], but not on FGF23 levels, nor other biomarkers. The follow-up prevalences of osteopenia and osteoporosis were 70% and 48% (p = 0.27 and p = 0.61, respectively). No bone fractures were observed. Dapagliflozin use over 24 weeks in patients on dialysis was independently associated with lowered serum Klotho levels, without effects in other bone biomarkers or related outcomes.