Impact of SGLT2i on bone health in patients with lupus nephritis: randomized double blinded placebo-controlled clinical trial.

Background: Patients with systemic lupus erythematosus (SLE) commonly experience osteoporosis and are at increased risk of bone fractures. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown promising cardiovascular and renal benefits in patients with kidney disease; however emerging evidence suggests that they may negatively impact bone health. This study aims to investigate the impact of SGLT2i on bone metabolism in patients with lupus nephritis (LN).

Methods: This is a randomized, double-blinded placebo-controlled clinical trial, including 84 adult patients with biopsy-proven LN and estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73m². Patients were randomized 1:1 and stratified according to age and gender to Dapagliflozin (10 mg daily) or placebo groups. Serum creatinine, eGFR, urinary protein-creatinine, calcium-creatinine, and phosphorus-creatinine ratios 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, procollagen type 1 N-terminal propeptide) and bone resorption markers (tartrate-resistant acid phosphatase 5b and Sclerostin). Moreover, quantitative computed tomography was used to assess volumetric bone mineral density.

Results: Participants had a mean age of 38 ± 7 years, with no significant baseline differences between groups. By the end of the study, there were no significant differences in kidney function or bone turnover biomarkers between the dapagliflozin and placebo groups after adjusting for baseline values. Only the lumber spine 3 (L3) T score of the quantitative computed tomography parameters was significantly better in the dapagliflozin group compared to the placebo group (P = 0.017). In a linear mixed model analysis, dapagliflozin was associated with a significant unadjusted decline in lumbar spine bone mineral density over one year, but this effect was attenuated and became non-significant after adjusting for age, steroid dose, and gender.

Conclusions: Dapagliflozin did not significantly affect bone and mineral metabolism in patients with lupus nephritis over a 12-month period. These findings suggest that dapagliflozin is unlikely to have adverse effects on bone health in patients with lupus nephritis, though further research is warranted to confirm these results over longer periods in a larger cohort.