Abstract: TH-PO160
DKK1 Expression in Osteocytes in Patients with Type 2 Diabetes and CKD-MBD
Session Information
- CKD-MBD: Clinical
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Deus, Aline Alves, Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Silva, Cleonice, Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Oliveira, Ivone Braga de, Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- dos Reis, Luciene, Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Dominguez, Wagner, Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Moyses, Rosa M.A., Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Jorgetti, Vanda, Laboratorio de Fisiopatologia Renal, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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.
| 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 |
Funding
- Other NIH Support