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Abstract: TH-PO527

Analysis of Cortical Bone Transcriptome Reveals Suppression of Bone Formation Pathways by Iron Therapy in Experimental CKD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic


  • Patino, Edwin, Weill Cornell Medical College, New York, New York, United States
  • Doty, Stephen B., Hospital for Special Surgery, New York, New York, United States
  • Bhatia, Divya, Weill Cornell Medical College, New York, New York, United States
  • Tan, Adrian Yingcai, Weill Cornell Medical College, New York, New York, United States
  • Choi, Mary E., Weill Cornell Medical College, New York, New York, United States
  • Akchurin, Oleh M., Weill Cornell Medical College, New York, New York, United States

Iron has been implicated in bone physiology and bone disorders. Most anemic patients with CKD require iron therapy. Iron excess has been shown to cause loss of bone mass in patients without CKD. However, the effects of iron therapy on the pathways underlying development of CKD-MBD remain largely unknown.


CKD was induced in mice by a 0.2% adenine diet, starting at 3 weeks of age. Femurs, kidneys, and blood were harvested at 3- and 8-week time-points in 4 groups of mice:
- CTR: controls without CKD
- CKDnoFe: untreated CKD
- CKDPOFe: CKD + 0.5% carbonyl iron diet
- CKDIPFe: CKD + weekly intraperitoneal injections of iron dextran, 0.5g/kg
Femurs were analyzed by micro-CT and histology. RNA was extracted from femur diaphyses harvested at 3 weeks. RNA sequencing was performed on Illumina HiSeq4000 with single-end 50 bps and analyzed using STAR (V2.5.2) and DESeq2 package.


By 3 weeks of experimental period, CKDnoFe mice developed renal injury and fibrosis and were mildly anemic. CKDPOFe and CKDIPFe mice did not have anemia at 3 weeks. No changes in bone microarchitecture were yet detected at 3 weeks in any group.
At 8 weeks, CKDnoFe mice displayed progression of anemia and loss of the cortical bone volume. Compared to the CKDnoFe group, CKDPOFe and CKDIPFe mice had milder anemia, but more severe bone loss at 8 weeks.
The expression of genes implicated in both bone formation (Wnt16, Wnt2b, Dmp1, Mmp13, Spp1, Ank) and bone resorption (Ctsk, Acp5, Calcr, Clcn7, Slc4a2) was higher in CKDnoFe than in CTR, consistent with increased bone turnover. In CKDPOFe and CKDIPFe groups, the expression of genes implicated in bone formation was lower than in CKDnoFe. At the same time, the expression of osteoclast genes associated with bone resorption was similar between CKDnoFe, CKDPOFE, and CKDIPFe groups.


In this model of CKD, both oral and parenteral iron therapy affected bone transcriptome before changes in bone microarchitecture. These transcriptional effects of iron, consistent with the suppression of bone formation pathways, without a corresponding effect on bone resorption pathways, likely represent early events in the process of bone loss associated with iron therapy in CKD. Our findings warrant attention to the potential unrecognized effects of iron on bone health in patients with CKD.


  • NIDDK Support