SGLT2 inhibitors and bone health in CKD

Chronic kidney disease ( CKD) poses a major threat to global health.With a prevalence of > 10%, CKD is estimated to be among the leading causes of premature death.The introduction of sodium glucose cotransporter 2 inhibitors ( SGLT2i) has had a considerable impact on disease progression, life-expectancy, and quality of life of patients with CKD, independent of underlying cause [1 ].Consequently, screening programs for CKD in the general population have become cost-effective [2 ].While initially developed for the treatment of diabetes mellitus type 2 ( T2DM) , clinical trials in CKD patients have demonstrated impressive effectiveness of SGLT2i to prevent CKD progression, cardiovascular complications, and premature death, independent of DM status or the presence of proteinuria.SGLT2i are generally well tolerated.Adverse effects reported in clinical trials and post-market surveillance include urinary tract infections, dehydration, and diabetic ketoacidosis.Early observations of an increased fracture risk and decreased bone mineral density ( BMD) were alarming but could not be reproduced consistently in later studies.Fracture incidence is increased in all stages of CKD, resulting in reduced quality of life, loss of patient autonomy, and increased mortality.The Kidney Disease: Improving Global Outcomes ( KDIGO) initiative has recently introduced the term CKD-associated osteoporosis, which summarizes the underlying processes, combining CKD-specific disturbances of bone turnover, mineralization, volume, and material properties with established causes of primary and secondary osteoporosis [3 ].This new definition opens for novel therapeutic strategies to reduce fracture risk in CKD, including the use of interventions targeting bone directly.It will also improve the understanding of the clinical consequences of interventions that affect mineral metabolism in CKD.