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Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray absorptiometry (DXA), is used to assess bone brittleness. The height-adjusted BMD Z-score (BMDHAZ) is calculated in children and adolescents with OI to reduce the confounding factor of short stature. However, even with the BMDHAZ, severity evaluation in children and adolescents with OI is challenging because certain abnormalities in bone quality cannot be accurately assessed by BMD analysis. The trabecular bone scores (TBS) and bone mineral apparent density (BMAD), which represent the structural integrity of bone and bone-size-associated BMD, respectively, are associated with fracture risk. Recently, age- and sex-specific reference ranges have been reported, enabling the calculation of Z-scores for children. To evaluate which density measurements show the highest correlation with fracture risk, we analyzed the associations between the Z-scores of TBS, BMAD, and BMDHAZ, fracture rate, and genetic variants. We retrospectively reviewed 42 participants with OI aged 5 to 20 years who underwent DXA. COL1A1/2 pathogenic variants were detected in 41 of the 42 participants. In participants with nonsense and frameshift variants (n = 17) resulting in haploinsufficiency and mild phenotype, the TBS Z-score was negatively correlated with fracture rate (FR) (r = -0.50, p = 0.042). In participants with glycine substitution (n = 9) causing the severe phenotype, the BMAD Z-scores were negatively correlated with FR (r = -0.74, p = 0.022). No correlation between the BMDHAZ and FR was observed in both groups. These findings suggest that the TBS and BMAD are useful in assessing children and adolescents with OI with specific genetic variants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ohata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Takuo Kubota received a scholarship donation from Teijin Pharma. Keiichi Ozono received honoraria from Kyowa Kirin, Alexion, and Novo Nordisk Pharma. The other authors have nothing to declare.

A previously developed current swimming pool for mice has been used to evaluate many food components that enhance endurance exercise performance. In this article, to improve reproducibility, reliability and sensitivity of this assay system, we improved the spout part to generate a uniform current and divided the pool into six lanes to avoid physical interference between swimming mice. The stability of the current flow was assessed by measuring the surface current speed and water volume from the spout part. Maximum swimming times of ddY and BALB/c mice were measured to assess the reproducibility of the maximum swimming time. The improvement in sensitivity compared to the original equipment was estimated under three physiological conditions: low carbohydrate diet feeding, low blood hemoglobin level, and carbohydrate supplementation during exercise. The new spout part improved uniformity and quick adjustment of surface current, yielding an increase of workload in a stepwise manner during swimming. Exercise workload was increased in proportion to surface current speed, as evidenced by cadence of kicks and serum lactic acid levels. The improved swimming pool showed higher reproducibility of swimming time until fatigue (p<0.0001). Correspondence between blood hemoglobin concentration and swimming time was improved in the swimming pool. The improved swimming pool yielded higher sensitivity for low carbohydrate diet feeding (p<0.0001) and carbohydrate supplementation during exercise (p<0.01) compared to the original swimming pool. The improvement of the swimming pool achieved higher sensitivity and reproducibility in assessing various diet and food components compared to the original swimming pool.