Bone Abstracts

Children with long-standing chronic kidney disease (CKD) display clinical symptoms of bone disease, including boney deformities and fractures, which contribute to long-standing disability. Bone biopsy is the only available method for assessing all three recommended areas of bone histology (turnover, mineralization, and volume) and new techniques in human bone tissue analysis have shed light on the progression of renal ROD throughout the course of CKD, including its early stages, as well as on the alterations in cell biology that accompany ROD.

Recent studies have identified that bone expression of fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1) and sclerostin (SOST) increase early in the course of CKD and are linked to abnormalities in bone turnover an mineralization skeletal mineralization, thus defining osteocytes as endocrine cells which generate hormones that affect bone healthy. In contrast to patients with normal kidney function, FGF23 processing and osteocyte biology appear to change with a progressive decline in kidney function. Indeed, although circulating FGF23 undergoes cleavage in patients with normal kidney function and in those with mild CKD, the majority of circulating FGF23 in dialysis patients is in its full-length form. Changes in circulating mineral ion and hormone concentrations may play a significant role in osteocytic protein expression as CKD advances. Current data suggest that increasing PTH levels suppress osteocytic SOST expression and that circulating phosphorus and PTH both increase FGF23 concentrations. Vitamin D sterols, the most common therapy for controlling secondary hyperparathyroidism and bone turnover, also alters osteocytic protein expression. The effect of these changes on long-term outcomes, including on the systemic effects of altered mineral metabolism in CKD (i.e. cardiac morbidity and mortality), remain to be determined.