title: Increased heterogeneity of bone matrix mineralization in pediatric patients prone to fractures: a biopsy study.
abstract: 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.
authors.affiliation: Bone and Cartilage Research Unit (BCRU), University of Eastern Finland, Kuopio, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Inari S
authors.initials: IS
authors.lastname: Tamminen
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Misof
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Mervi K
authors.initials: MK
authors.lastname: Mäyränpää
authors.forename: Mikael J
authors.initials: MJ
authors.lastname: Turunen
authors.forename: Hanna
authors.initials: H
authors.lastname: Isaksson
authors.forename: Heikki
authors.initials: H
authors.lastname: Kröger
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
mesh_terms: D000293:Adolescent; D001706:Biopsy; D015519:Bone Density; D002648:Child; D005260:Female; D050723:Fractures, Bone / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology*
keywords: BMDD; BONE MINERALIZATION DENSITY DISTRIBUTION; CHILDREN; HISTOMORPHOMETRY; IDIOPATHIC OSTEOPOROSIS; QBEI; QUANTITATIVE BACKSCATTERED ELECTRON IMAGING; VERTEBRAL FRACTURE