Increased heterogeneity of bone matrix mineralization in pediatric patients prone to fractures: a biopsy study
Inari S Tamminen1, Barbara M Misof, Paul Roschger
1Bone 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.
Insights
Children with idiopathic osteoporosis (IOP) show increased bone mineralization heterogeneity. This suggests altered bone turnover contributes to fragility fractures in pediatric patients with suspected IOP.
Area of Science:
- Pediatric Endocrinology
- Bone Biology
- Skeletal Health
Background:
- Idiopathic osteoporosis (IOP) in children presents with fragility fractures and low bone mineral density.
- Understanding the underlying bone characteristics in pediatric IOP is crucial for diagnosis and management.
Purpose of the Study:
- To assess bone mineralization density distribution (BMDD) using quantitative backscattered electron imaging (qBEI) in children with suspected IOP.
- To compare BMDD in these children with normal reference data and correlate findings with clinical and histomorphometric parameters.
Main Methods:
- Analysis of entire cross-sectional areas of transiliac bone biopsy samples from 24 children (aged 6.7-16.6 years) with suspected IOP.
- Quantitative backscattered electron imaging (qBEI) was used to measure cancellous (Cn) and cortical (Ct) BMDD.
- Comparison with normal reference BMDD data and correlation with histomorphometry and serum bone turnover markers.
Main Results:
- Children with suspected IOP exhibited significantly higher heterogeneity of mineralization in both cancellous (Cn.CaWidth +23%) and cortical (Ct.CaWidth +15%) bone compared to controls.
- Increased percentages of low mineralized cancellous bone (Cn.CaLow +35%) and highly mineralized cortical bone (Ct.CaHigh +82%) were observed.
- Cortical bone width and low mineralization were positively correlated with mineralizing surface per bone surface (MS/BS) and serum bone turnover markers.
Conclusions:
- Children with suspected IOP demonstrate altered bone mineralization patterns, characterized by increased heterogeneity.
- Enhanced variation in bone turnover and formation likely contributes to this mineralization heterogeneity.
- The causal relationship between mineralization heterogeneity and bone fragility in pediatric IOP requires further investigation.
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.
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