Accelerated mineralization kinetics in children with osteogenesis imperfecta type 1.

Abstract

Not much is known about the time course of mineralization in newly formed bone from healthy individuals nor in patients with bone disease. To investigate the early phase of mineral accumulation in human bone, we measured the mean mineralization content between double fluorescence labels (CaYoung) with quantitative backscattered electron imaging (qBEI) in human transiliac biopsy samples. Fluorescent labels for histomorphometric evaluation were administered over two 2-day periods separated by a 10-day-free interval, 4–5 days before biopsy procedure. We compared n = 19 children with osteogenesis imperfecta type I (OI, 6 girls/13 boys, age-range 2.2–14.1 years) with both a reference group of n = 38 healthy children (REF, 24 girls/14 boys, age-range 1.5–20.9 years) and an age-matched subgroup ( n = 17) of the latter (CON, 5 girls/12 boys, age-range 2.0–14.7 years). We observed significantly higher levels of CaYoung in OI type I compared to CON and REF in both cortical bone (Ct.CaYoung, +8.3 % and +7.0 %, respectively) and cancellous bone (Cn.CaYoung, +6.5 % and +4.9 %, all p < 0.001). When comparing cortical and cancellous compartments intra-individually, we found a significantly higher Cn.CaYoung than Ct.CaYoung in REF (2.3 ± 2.9 %, p < 0.001), but not in the OI group (0.6 ± 1.6 %, not significant). In the REF group, n = 7 samples also contained double labels in primary woven bone (which is deposited at the external cortex during growth/lateral drift of the iliac crest). This primary woven bone in REF had a higher CaYoung than secondary osteonal bone (4.9 ± 2.7 %). Our findings suggest that bone in OI has an accelerated mineral accumulation compared to healthy bone. This is reflecting the overall increased bone mineralization in OI as reported previously, and indicates that the higher levels of mineralization than those seen in healthy individuals are already achieved in OI type I early after onset of mineralization. • We measured mineralization kinetics by the combination of qBEI and CLSM imaging. • The mineral content of bone between the double labels (CaYoung) was analyzed. • CaYoung was increased in young patients with OI compared to healthy children. • In healthy children but not in OI, CaYoung was higher in spongiosa than in cortex.