| First Author | Davies MR | Year | 2005 |
| Journal | J Am Soc Nephrol | Volume | 16 |
| Issue | 4 | Pages | 917-28 |
| PubMed ID | 15743994 | Mgi Jnum | J:110048 |
| Mgi Id | MGI:3630368 | Doi | 10.1681/ASN.2004100835 |
| Citation | Davies MR, et al. (2005) Low turnover osteodystrophy and vascular calcification are amenable to skeletal anabolism in an animal model of chronic kidney disease and the metabolic syndrome. J Am Soc Nephrol 16(4):917-28 |
| abstractText | LDL receptor (LDLR)-null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome, have vascular calcification (VC) worsened by chronic kidney disease (CKD) and ameliorated by bone morphogenetic protein-7 (BMP-7), an efficacious agent in treating animal models of renal osteodystrophy. Here, LDLR-/- high-fat-fed mice without CKD were shown to have significant reductions in bone formation rates, associated with increased VC and hyperphosphatemia. Superimposing CKD resulted in a low turnover osteodystrophy, whereas VC worsened and hyperphosphatemia persisted. BMP-7 treatment corrected the hyperphosphatemia, corrected the osteodystrophy, and prevented VC, compatible with skeletal phosphate deposition leading to reduced plasma phosphate and removal of a major stimulus to VC. A pathologic link between abnormal bone mineralization and VC through the serum phosphorus was supported by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in this model of the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to low bone turnover rates, producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through deposition of phosphate and increased bone formation. |
