Cross-sectional study shows that impaired bone mineral status and metabolism are found in non mosaic triple X syndrome Short running title : Bone status in triple X syndrome

Aim. The effect of a supernumerary X chromosome on bones has not been reported and this study evaluated bone mineral status and metabolism in non-mosaic triple X syndrome. Methods. This cross-sectional study comprised 19 girls, with a median age of 10.9 years, with nonmosaic triple X syndrome and a control group matched for age and body size. We studied ionised and total calcium, phosphate, parathyroid hormone (PTH), 25hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels and urinary deoxypyridinoline concentrations. We also measured the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) Z-scores. Results. Patients with non-mosaic triple X showed significantly reduced AD-SoS (p<0.005) and BTT Z-scores (p<0.0001) compared to the control group and these results persisted when we divided the sample into prepubertal and pubertal patients (p<0.05). These patients also had significantly reduced ionised calcium (p<0.005) and 25(OH)D levels (p<0.005) and higher phosphate (p<0.0001) and PTH (p<0.0001) levels. Conclusion. Subjects with non-mosaic triple X syndrome exhibited a significant impairment in bone mineral status and metabolism similar to other X polisomy, such as Klinefelter syndrome. This suggests the presence of a primary bone deficit and the need for regular and close monitoring of these subjects.