DKK1 Expression in Osteocytes in Patients with Type 2 Diabetes and CKD-MBD

Background: Chronic kidney disease mineral bone disorder (CKD-MBD) is influenced by factors such as age, race, CKD etiology, hormones, dialysis modality. Proteins expressed in osteocytes emerged as important players in bone tissue of CKD-MBD patients as FGF23, sclerostin, DKK1, RANKL, and OPG. However, little is known about the effects of these proteins on bone tissue in patients with type 2 diabetes (DM2) and CKD-MBD. Methods: 30 DM2 hemodialysis patients were matched with CKD patients due to other etiologies by age, sex, and time on dialysis. All underwent bone biopsies with histomorphometric analysis. Osteocyte protein expression for DMP1, MEPE, Sclerostin, FGF23, RANKL, and DKK1 was studied through immunohistochemistry. Results: Table 1 shows that DM2 patients have lower PTH and higher BMI. Bone histomorphometry showed that bone formation parameters and Oc.S/BS were lower in DM patients. We found a significant increase in DKK1 expression in DM2 patients. Conclusion: DKK1, known as an inhibitor of Wnt/Bcatenin pathway, was increased in bone tissue of DM patients. Although BV/TV wasn't different between the groups, formation parameters were decreased in DM patients, suggesting that DKK1 may be involved in low bone turnover observed in DM patients. Funding: Other NIH Support - Fapesp - Fundação de Amparo à Pesquisa do Estado de São Paulo - Diabetic Mellitus(n=30) Non-diabetic(n=30) p Age,year 59.8±9.1 58.4±9.1 0.57 Sex,men 19 (63%) 19 (63%) 1.00 Hemodialysis time,month 21.5 (29;60) 25.5 (41.5;55.5) 0.28 BMI,kg/m2 24.5 (26.4;29.5) n=22 20.9 (24.1;25.6)n=12 0.007 Calcium,mg/dl 8.3 (9.0;9.7) 8.5 (9.4;9.9) 0.33 Phosphorus,mg/dl 5.7±1.5 5.3±1.3 0.21 Alk phosphatase,UI/l 84.5 (116;220.5) 100 (163;271) 0.28 Parathyroid hormone,pg/ml 225 (325;831) 367 (955;1513) 0.012 DKK1,% 0.56 (0;3.03) 0.08 (0;0.40) 0.03 Sclerostin,% 7.70 (1.3;23.3) 3.45 (1.44;6.92) 0.079 Osteocytes,n 530 (204;806) 673 (325;1062) 0.128 BV/TV,% 16.9 (12.9;22.5) 17.7 (12.7;29.6) 0.31 OV/BV,% 1.79 (0.9;6.6) 6.8 (3.9;12.4) 0.004 O.Th,µm 6.2 (4.9;8.9) 10.8 (8.0;15.1) 0.0001 OS/BS,% 21.6 (9.5;45.0) 40.6 (29.4;49;7) 0.03 Ob.S/BS,% 4.5 (1.1;12.3) 9.8 (6.0;16.0) 0.03 Oc.S/BS,% 0.57 (0.1;1.3) 1.75 (0.2;3.2) 0.047 BFR/BS, µm3/µm2/day 0.03 (0.01;0.08) 0.05 (0.02;0.09) 0.43 Mlt,day 65.3 (28.5;205.3) 85.6 (39.7;161.8) 0.63