The effect of sodium-glucose cotransporter-2 inhibitors on bone mineral metabolism markers in patients with mild to moderate diabetic nephropathy

Introduction and Aim: Sodium glucose transporter 2 inhibitors promote natriuresis and osmotic diuresis while inhibiting glucose reabsorption from the proximal tubule. It has been suggested that dapagliflozin, due to its renal tubular mechanism of action, can alter calcium and phosphate metabolism, with minor increases in serum magnesium, phosphate, and parathormone. This study looked at how dapagliflozin affected the markers FGF-23, hydroxyproline, osteoprotegerin, and sclerostin, which are involved in bone mineral metabolism, vascular events, and inflammation in patients with stage 2-4 CKD. Materials and Methods: Eighty outpatients from the nephrology outpatient clinic were randomly assigned to one of two groups. Those who began SGLT-2i treatment were classified as group 1, while those who continued their current diabetes treatment were classified as group 2. Age, gender, comorbid diseases, drugs used, creatinine, urea, eGFR, sodium, potassium, calcium, albumin, phosphorus, magnesium, hemogram, serum FGF-23, sclerostin, OPG, and hydroxyproline levels were all measured. After 12 weeks of follow-up, the parameters of the two groups, as well as the initial and final values of group 1, were compared. Results: The baseline HbA1c (p=0.0001) and creatinine (p=0.007) levels in the dapagliflozin group were significantly higher. While there was no difference in uric acid levels at the start, uric acid levels were significantly lower in the dapagliflozin arm at the end of the third month (p=0.004). While there was no difference in FGF-23 and sclerostin levels between the two groups at the start, these two values were significantly lower in the dapagliflozin arm at the end of three months (p=0.009 and p=0.004, respectively). There was no difference in OPG and hydroxyproline levels between the two groups (p=0.09 and p=0.88, respectively). The levels of OPG, FGF-23, and sclerostin in the dapagliflozin group were significantly lower before and three months after treatment (p=0.0001 in all), but the decrease in hydroxyproline was not significant (p=0.104). Conclusions: CKD is a disease with a high morbidity and mortality rate, a low rate of early detection, and a negative impact on quality of life. Cardiovascular disease is the leading cause of morbidity and mortality in diabetic nephropathy-related CKD. The mechanisms by which SGLT-2i has shown these effects, which have been shown in many clinical studies to have very positive effects on cardiovascular outcomes and CKD progression, have not been fully explained. And also, bone mineral disorders are a major cause of morbidity in CKD patients, and the impact of SGLT-2i on this issue is unknown. In our study, we found that FGF-23, sclerostin, and OPG levels, which are bone markers involved in the pathogenesis of conditions like inflammation and vascular calcification in CKD, decreased significantly after dapagliflozin treatment. This finding could point to the mechanisms underlying SGLT-2i's cardiovascular benefits and serve as a foundation for future research. Key words: SGLT-2i, osteoprotegerin, FGF-23, sclerostin, hydroxyproline