Increased Heterogeneity of Bone Matrix Mineralization in Pediatric Patients Prone to Fractures: A Biopsy Study

Idiopathic osteoporosis (IOP) in children is characterized by fragility fractures and/or low bone mineral density in otherwise healthy individuals. The aim of the present work was to measure bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) in children with suspected IOP. Entire cross-sectional areas of transiliac bone biopsy samples from children (n=24, 17 boys; aged 6.7-16.6 years) with a history of fractures (n=14 with at least one vertebral fracture) were analyzed for cancellous (Cn) and cortical (Ct) BMDD. Outcomes were compared with normal reference BMDD data and correlated with the patients' clinical characteristics and bone histomorphometry findings. The subjects had similar average degree but significantly higher heterogeneity of mineralization in both Cn and Ct bone (Cn.CaWidth +23%, Ct.CaWidth +15%, p<0.001 and p=0.002, respectively), together with higher percentages of low mineralized cancellous (Cn.CaLow +35%, p<0.001) and highly mineralized cortical bone areas (Ct.CaHigh +82%, p=0.032). Ct.CaWidth and Ct.CaLow were positively correlated with mineralizing surface per bone surface (MS/BS; a primary histomorphometric determinant of bone formation) and with serum bone turnover markers (all p<0.05). The correlations of the mineralization heterogeneity with histomorphometric and serum bone turnover indices suggest that an enhanced variation in bone turnover/formation contributes to the increased heterogeneity of mineralization. However, it remains unclear whether the latter is cause for, or the response to the increased bone fragility in these children with suspected IOP. (c) 2014 American Society for Bone and Mineral Research

Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings

Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis. Iliac crest biopsies were obtained from 19 children (7.6-18.8 years, 11 male) who had undergone kidney (n = 6), liver (n = 9), or heart (n = 4) transplantation a median 4.6 years (range 0.6-16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy. Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below -2.0. Histomorphometric analyses showed low trabecular bone volume (< -1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease. There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients

Development of new criteria for cortical bone histomorphometry in femoral neck: intra- and inter-observer reproducibility

Histomorphometry is commonly applied to study bone remodeling. Histological definitions of cortical bone boundaries have not been consistent. In this study, new criteria for specific definition of the transitional zone between the cortical and cancellous bone in the femoral neck were developed. The intra- and inter-observer reproducibility of this method was determined by quantitative histomorphometry and areal overlapping analysis. The undecalcified histological sections of femoral neck specimens (n = 6; from men aged 17-59 years) were processed and scanned to acquire histological images of complete bone sections. Specific criteria were applied to define histological boundaries. "Absolute cortex area" consisted of pure cortical bone tissue only, and was defined mainly based on the size of composite canals and their distance to an additional "guide" boundary (so-called "preliminary cortex boundary," the clear demarcation line of density between compact cortex and sparse trabeculae). Endocortical bone area was defined by recognizing characteristic endocortical structures adjacent to the preliminary cortical boundary. The present results suggested moderate to high reproducibility for low-magnification parameters (e.g., cortical bone area). The coefficient of variation (CV %) ranged from 0.02 to 5.61 in the intra-observer study and from 0.09 to 16.41 in the inter-observer study. However, the intra-observer reproducibility of some high-magnification parameters (e.g., osteoid perimeter/endocortical perimeter) was lower (CV %, 0.33-87.9). The overlapping of three histological areas in repeated analyses revealed highest intra- and inter-observer reproducibility for the absolute cortex area. This study provides specific criteria for the definition of histological boundaries for femoral neck bone specimens, which may aid more precise cortical bone histomorphometry