Changes of the Bone Metabolism Markers and Body Composition in Nonalcoholic Fatty Liver Disease by the SGLT2 inhibitor

We reported that histological improvement was confirmed after 24 weeks of Canagliflozin (CANA) therapy in nonalcoholic fatty liver disease (NAFLD). While increase of the fracture according to the CANVAS Program was reported. In type 2 diabetes patients with NAFLD (T2ND) who showed histological improvement by using CANA (100 mg/ day), we investigated the bone metabolism markers and the body composition (measured using an INBODY770) after at least 1 year of same treatment. The changes of the parameters (Liver enzymes, serum bone specific alkaline phosphatase (BAP: nMBCE/mMCr) and urinary N-telopeptide of collagen type-I (uNTx: U/L)) were investigated before starting treatment (Pre), after 24 weeks (24W), and at the end of follow-up (Post). Six patients (4 men and 2 women, aged 55.3±7.2 years, HbA_1c8.4±2.0%, BMI: 28.6±2.2 and the duration 8.0±7.7 years) were able to evaluate bone metabolism, and the follow-up period was 1.3±0.2 years. HbA1c, Liver enzymes and Ferritin levels showed further improvement after more than 24 weeks. The Post-Pre difference of bone minerals (BMi) showed a significant positive correlation with the change of skeletal muscle mass and a significant negative correlation with HbA1c at 24W. In 2 cases that the rate of skeletal muscle mass loss for total body weight loss at 24W was ≥ 30%, the Post BMi decreased more than 5%. There was no correlation with the improvement of the NAFLD activity score by the liver biopsy. BAP levels didn’t change during CANA treatment, while uNTx levels increased in all patients at 24W, but almost returned to Pre levels at Post. (uNTx: Pre 31.3(8.2)/ 24W 425.9(344.5)/ Post 38.1(3.9)). The uNTx levels showed a pronounced increase from Pre (24.0) to 24W (2143.3) in 1 patient with a history of fracture. During long-term CANA therapy, there was ongoing improvement of the liver inflammation markers in T2ND, while these findings suggest that early changes of bone resorption by CANA therapy predict the subsequent state of bone metabolism.