Bone Abstracts

Objectives: FGF23 is expressed in clusters of osteocytes at the trabecular periphery suggesting that FGF23-expressing osteocytes are confined to specific basic multicellular units (BMUs) at the trabecular surface. Higher numbers of FGF23-expressing osteocytes are found in chronic kidney disease (CKD) patients with preserved skeletal mineralization indices. We thus combined immunohistochemistry and quantitative backscattered electron imaging (qBEI) to explore the hypothesis that FGF23 expression is confined to BMUs that have successfully transitioned from primary to an early phase of secondary mineralization in CKD bone.

Methods: Histomorphometric analysis and immunohistochemistry for FGF23 expression were performed in un-decalcified bone from 4 patients (18–25 years) treated with maintenance dialysis (CKD5D). BE images were captured by scanning the entire cross-sectional area of the biopsy sample block with a resolution of 1.8 μm/pixel and mapped according to the FGF23 staining observed in the adjacent histological section. Mean calcium content was evaluated in selected bone packets and bone mineralization density distribution (BMDD) was assessed in trabecular and cortical compartments.

Results: Bone turnover was low in all patients although serum PTH levels were high in 3 probands. No osteomalacia was noted on histomorphometry. The average calcium concentration (CaMean) was within normal range or increased up to +7.4% in trabecular bone and up to +11.4% in the cortical compartment. Bone packets with high FGF23 expression were located at trabecular and osteonal surfaces, showed no features of active bone formation and were all mineralized above 18 weight% calcium. In the patient with low serum PTH concentrations, the peripheral matrix surrounding FGF23-expressing osteocytes was mineralized above 27 weight% calcium and the bone packets were higher mineralized than the adjacent older ones. In all other samples, the highest calcium contents were found in the oldest bone packets, deep within the bone matrix, which did not surround FGF23-expressing osteocytes.

Conclusion: This pilot analysis suggests that FGF23 expression in CKD5D bone is confined to osteocytes in rather young BMUs, at the trabecular periphery and on osteonal surfaces, that have completed primary mineralization. Further studies are ongoing to evaluate the relationship between bone turnover, bone material properties, and FGF23 expression in the context of CKD.

Disclosure: The authors declared no competing interests.