Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome.

BACKGROUND: More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects. METHODS: In 232 women with Rett syndrome (mean age 13.8 ± 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe. RESULTS: As aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p < 0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations with respect to less severe mutations but the difference was not statistically significant. Moreover, subjects with Rett syndrome with more severe mutations present a higher prevalence of scoliosis (p < 0.05) and of inability to walk (p < 0.05). CONCLUSION: This study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.

In Type-2 Diabetes Subjects Trabecular Bone Score is Better Associated with Carotid Intima-Media Thickness than BMD.

Literature data reported that in elderly subjects, carotid intima-media thickness (IMT) was negatively associated with bone mineral density (BMD). Paradoxically, type-2 diabetes (T2DM) patients, despite having higher BMD, present an increased risk of fragility fractures and cardiovascular complications. Some studies have reported trabecular bone score (TBS), an index of trabecular bone quality, as possibly being reduced in T2DM. This study aimed to evaluate whether in T2DM subjects TBS was better associated with IMT with respect to BMD. In 131 consecutive T2DM subjects (55 men and 76 women; mean age: 60.0 ± 7.3 years) and 265 consecutive non-T2DM subjects (107 men and 158 women; mean age: 58.9 ± 7.8 years) we measured carotid IMT by high-resolution ultrasonography and BMD at lumbar spine (LS-BMD), at femoral neck FN-BMD and total hip TH-BMD; TBS was calculated using TBS iNsight software. LS-BMD, FN-BMD, and TH-BMD were all significantly higher in T2DM than in non-T2DM subjects, whereas TBS was significantly lower in T2DM subjects than in controls and inversely correlated with diabetes duration. In T2DM subjects multiple regression analysis showed that IMT was positively associated with age (b = 0.017; p < 0.001) and inversely associated with TBS (b = -0.473; p = 0.038). In non-T2DM subjects, only age was positively associated with IMT. To sum up, T2DM subjects present higher values of BMD and lower values of TBS with respect to non-diabetic controls. Moreover, in T2DM subjects TBS was found to be independently associated with carotid IMT. These findings suggest that TBS may not only capture bone fragility-related factors, but also some information associated with greater risk of developing cardiovascular diseases.