ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO481

Cross-Talk Between Vascular and Bone Tissues: Does Vascular Calcification Induce Bone Loss?

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Mace, Maria Lerche, Herlev Hospital, Herlev, Denmark
  • Gravesen, Eva, Rigshospitalet, Copenhagen, Denmark
  • Nordholm, Anders, Herlev Hospital, Herlev, Denmark
  • Morevati, Marya, Rigshospitalet, Copenhagen, Denmark
  • D'Haese, Patrick C., University Antwerp, Edegem, Belgium
  • Olgaard, Klaus, Rigshospitalet, Copenhagen, Denmark
  • Lewin, Ewa, Herlev Hospital, Herlev, Denmark
Background

Disturbances in bone homeostasis have been associated with development of vascular calcification. Results of epidemiological studies in general population and in CKD patients showed more severe progressive vascular calcifications were associated with greater bone loss and fractures. Our question was whether the presence of severe vascular calcification may have an impact on bone metabolism.

Methods

A novel model of isogenic aorta transplantation was used (ATX). Severe uremic vascular calcifications were induced in DA rats by 5/6 nephrectomy, high P diet and calcitriol. After 14 weeks the calcified abdominal aorta of the uremic rat was transplanted into a normal DA rat (n=16). Control groups were ATX of a normal aorta to normal rat (n=9) and age-matched rat (n=6). Rats were sacrificed 4 weeks after ATX and plasma biochemistry, bone and vessels were analyzed.

Results

The uremic donor rat suffered from severe kidney disease with disturbed mineral balance and its aorta had a high calcium content of 15.7±0.8 µg Ca/mg vs. none in the normal aorta. Control, normal ATX and calcified ATX rats had same levels of creatinine, Ca2+, phosphate, PTH, FGF23 and sclerostin. The calcified ATX rats had significant changes in mRNA of several bone markers compared to normal ATX and control rats such as alkaline phosphatase (3.26±0.29 vs. 1.56±0.32 & 0.86±0.12, both p<0.001), sclerostin (3.60±0.68 vs. 1.41±0.34 & 1.04±0.27, both p<0.01), RUNX2 (1.53±0.09 vs. 0.80±0.18 & 0.44±0.11, p<0.01, p<0.001), Osteocalcin (0.54±0.06 vs. 0.92±0.14 & 1.19±0.06, p<0.05, p<0.001), RANKL (0.40±0.05 vs. 1.91±0.36 & 2.43±0.30, p<0.01, p<0.001), cathepsin K (2.36±0.24 vs. 1.19±0.23 & 1.01±0.07, p<0.01, p<0.001), beta catenin (3.15±0.25 vs. 1.28±0.26 & 1.03±0.13, both p<0.001), collagen I (8.50±0.93 vs. 4.06±2.02 & 3.25±0.88, p<0.05, p<0.001), osteopontin (1.46±0.18 vs. 0.69±0.17 & 0.49±0.06, both p<0.01). Finally, bone mineral density (BMD) was significantly lower in calcified ATX rats compared to normal ATX and control rats (1576±5 vs. 1592±5 & 1613±6 mg/cc, both p<0.05).

Conclusion

These novel findings indicate the existence of a tissue crosstalk between vessels and bone. The presence of vascular calcifications has an impact on several pathways in bone and decrease BMD. Vascular calcification does induce bone loss.

Funding

  • Private Foundation Support