Bone ultrasonography in the longitudinal monitoring of bone status in patient with Rett’s syndrome

Rett Syndrome (RS), an X-linked neurodevelopmental disorder primarily affecting girls, is frequently characterized by osteopenia with a consequent increased risk of fragility fractures. In recent years there has been a growing interest in using Quantitative Ultrasound (QUS) for the evaluation of bone status. This study aimed to evaluate the usefulness of QUS in the monitoring RS parameters. Among the patients with RS referred to the Department of Child Neurology and Psychiatry we selected a cohort of 46 females (age range 5–30 years) for whom a follow-up of at least 4 years was available. In all at baseline and every 12 months over the 4-year study period we measured serum calcium, serum phosphate, alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D. At the same times we assessed QUS parameters at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). In our institution the precision was 0.8% for AD-SoS and 0.6% for BTT. The patients were divided into three groups: non-ambulatory (group 1; n = 11), with severe (group 2; n = 10) or mild-moderate (group 3; n = 25) ambulatory impairment. At baseline no significant differences in QUS parameters were found between the ambulatory and non-ambulatory patients. However, from the first year and thereafter during the whole 4-year study period, the non-ambulatory patients presented a reduction in both AD-SoS and BTT significantly (p < 0.01) higher with respect to the other 2 groups. At the end of the study the change in AD-SoS Z-score was-0.60 for group 1,-0.40 for group 2 and 0.10 for group 3. At baseline and at all follow-up time points alkaline phosphatase was significantly higher in non-ambulatory group. The RS patients were divided in tertiles on the basis of the dose of anticonvulsants (carbamazepine) and we found that at baseline both AD-SoS and BTT were significantly lower in the group with the higher dose with respect to the group with the lower dose of anticonvulsants (1838 vs. 1879 and 0.50 vs. 0.74 respectively). During the study period in the higher tertile BTT showed a tendency to decrease without reaching statistical significance. In conclusion QUS parameters seem to be a valuable tool in the monitoring of the patients with RS. The ambulatory ability and the use of anticonvulsants seem to be the main determinants of bone status in patients with RS.