# Impact of dapagliflozin on bone mineral metabolism in non-diabetic patients with chronic kidney disease: a randomized, double-blind, placebo-controlled study

## TL;DR

This study found that dapagliflozin, a kidney disease drug, does not significantly affect bone health in non-diabetic patients with chronic kidney disease.

## Contribution

The study provides preliminary evidence on the bone safety of dapagliflozin in non-diabetic CKD patients.

## Key findings

- Dapagliflozin significantly reduced proteinuria without affecting eGFR.
- No significant differences in bone turnover markers or bone mineral density were observed between groups.
- Both groups showed similar decreases in bone formation and resorption markers.

## Abstract

Sodium–glucose co-transporter 2 inhibitors have demonstrated renoprotective effects in patients with CKD. However, concerns remain regarding their potential effect on bone mineral metabolism. This study investigated the impact of dapagliflozin on bone health in non-diabetic patients with CKD.

This randomized, double-blind, placebo-controlled trial enrolled 100 non-diabetic adults with CKD and an estimated glomerular filtration rate (eGFR) of 25–75 ml/min/1.73 m2. Participants were randomized 1:1 to receive either dapagliflozin 10 mg daily or placebo for 12 months and stratified by age and eGFR. Serum creatinine, eGFR, urinary protein:creatinine ratio, calcium:creatinine ratio and phosphorus:creatinine ratio were measured at baseline and after 12 months. Bone health was assessed at the same time points using bone formation markers [bone-specific alkaline phosphatase (BSAP), total procollagen type 1 N-terminal propeptide (P1NP)] and bone resorption markers [carboxy-terminal telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRAP-5b)]. Moreover, quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD).

Participants had a mean age of 53.5 ± 11.1 years, with no significant baseline differences between groups. Dapagliflozin significantly reduced proteinuria compared with placebo (P = .012) without significantly affecting eGFR. Both groups experienced significant decreases in BSAP and TRAP-5b levels (P < .001), with no intergroup differences. P1NP remained stable in both groups. CTX-1 levels increased significantly in the placebo group (P = 0.032) but not in the dapagliflozin group without significant intergroup differences. No significant differences in vBMD or T-scores at any lumbar or total lumbar spine were observed between groups after 1 year.

This exploratory randomized controlled trial did not demonstrate any meaningful impact of dapagliflozin on either bone turnover or QCT markers. While these findings provide reassuring preliminary evidence, larger studies are needed to definitively establish long-term bone safety of dapagliflozin in non-diabetic patients with CKD.