Abstract: SA-PO902

Increased Bone FGF23 expression Is Linked to Impaired Osteocyte Maturation in CKD

Session Information

  • Mineral Disease: CKD-Bone
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1203 Mineral Disease: CKD-Bone

Authors

  • Wesseling-Perry, Katherine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Pereira, Renata C., David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Salusky, Isidro B., Mattel Children's Hospital, Los Angeles, California, United States
Background

Increased FGF23 expression and skeletal mineralization defects characterize bone in CKD. FGF23-expressing osteocytes are located in clusters at the trabecular periphery. Since young osteocytes are also at the trabecular periphery, we hypothesized that FGF23 is a marker of young osteocytes. We also hypothesized that increased numbers of young, FGF23-expressing, osteocytes reflect an adaptive response to impaired osteocyte maturation, the consequence of which is defective skeletal mineralization, in CKD.

Methods

We evaluated bone from 32 pediatric CKD patients (stages 2-4: n=12; stage 5: n=20). Patients were dichotomized based on the presence (n=13) or absence (n=19) of skeletal mineralization defects, defined by increased osteoid volume along with prolonged osteoid maturation time. Co-expression of FGF23 (FGF23(225-244); Quidel) with markers of osteocyte maturity (early osteocytes: e11/gp38 (ab25, Abcam); late osteocytes: MEPE(ab108073, Abcam)) was evaluated by immunofluorescence. Numbers of FGF23 and MEPE expressing osteocytes were evaluated by immunohistochemistry.

Results

FGF23 co-localized with e11/gp38 but did not co-localize with MEPE. Normal skeletal mineralization indices were associated with a 429 + 153% increase in numbers of FGF23-expressing osteocytes (p<0.05 from control values; p<0.05 from patients with skeletal mineralization defects). Numbers of MEPE-expressing osteocytes did not differ between groups or between CKD patients and controls.

Conclusion

FGF23 is a marker of young osteocytes. Normal mineralization indices in CKD are associated with a robust increase in young osteocytes. Impaired osteocyte maturation may precede and contribute to the development of skeletal mineralization defects and secondary hyperparathyroidism in CKD.

A) Colocalization of FGF23 and e11 in iliac crest. B) Increased numbers of FGF23-expressing osteocytes, but not MEPE-expressing osteocytes, in CKD patients with normal mineralization indices.

Funding

  • NIDDK Support