Abstract Children and adolescents with end-stage kidney disease (ESKD) have a high prevalence of bone deformities and fractures, even when bone histomorphometric measures of bone formation, mineralization, and volume are within normal range. We postulated that bone matrix quality and osteocyte differentiation are impaired in ESKD in ways which might be not reflected by alterations in surface-based cell activity. We assessed bone turnover, mineralization, and volume by traditional histomorphometry in bone biopsy cores from 24 adolescent patients with ESKD. We stained sequential sections of the same cores for apoptosis (TUNEL staining) and for osteocyte-specific maturation markers (sclerostin, DMP1, and FGF23). We then performed quantitative backscattered electron imaging (qBEI) to assess bone mineralization density distribution (BMDD) on the whole bone surface and additionally in bone packets containing FGF23-expressing osteocytes. Increased amounts of osteoid (OV/BV4.7%) and a true defect in bone surface mineralization (O.Th10 μm combined with MLT27.1 days) were detectable by histomorphometry in 29% and 17% of bone samples, respectively. By contrast, qBEI detected an excess in primary mineralizing bone (TbCaLow6.8%) in 88% of samples and abnormally low bone matrix mineralization (TbCaMean22.1 wt% calcium) in 75% of samples. Osteocyte lacunar density and size were within normal range. Unexpectedly, higher numbers of FGF23-expressing osteocytes and a more elongated osteocyte lacunar shape were found in bone samples with greater matrix mineralization. In conclusion, matrix mineralization defects, which are not detected by traditional histomorphometry, are highly prevalent in ESKD bone and reflect poor bone matrix maturation. High numbers of FGF23-expressing osteocytes are found in bone with the most appropriate matrix maturation characteristics. This differs from the bone characteristics of individuals with normal kidney function, in whom large amounts of FGF23 result in low circulating phosphate levels, which in turn triggers severe osteomalacia and hypomineralized peri-osteocytic lesions.
Fratzl-Zelman et al. (Fri,) studied this question.