DXA measurements in Rett syndrome reveal small bones with low bone mass.

Low bone mass is reported in growth-retarded patients harboring mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene causing Rett syndrome (RTT). We present the first study addressing both bone mineral density (BMD) and bone size in RTT. Our object was to determine whether patients with RTT do have low BMD when correcting for smaller bones by examination with dual-energy X-ray absorptiometry (DXA). We compared areal BMD (aBMD(spine) and aBMD(total hip) ) and volumetric bone mineral apparent density (vBMAD(spine) and vBMAD(neck) ) in 61 patients and 122 matched healthy controls. Further, spine and hip aBMD and vBMAD of patients were associated with clinical risk factors of low BMD, low-energy fractures, MECP2 mutation groups, and X chromosome inactivation (XCI). Patients with RTT had reduced bone size on the order of 10% and showed lower values of spine and hip aBMD and vBMAD (p < .001) adjusted for age, pubertal status, and body mass index (BMI). aBMD(spine) , vBMAD(spine) , and aBMD(total hip) were associated with low-energy fractures (p < .05). Walking was significantly associated to aBMD(total hip) and vBMAD(neck) adjusted for age and body mass index (BMI). Further, vBMAD(neck) was significantly associated to a diagnosis of epilepsy, antiepileptic treatment, and MECP2 mutation group, but none of the associations with vBMAD(neck) remained clinically significant in a multiple adjusted model including age and BMI. Neither aBMD(spine) , vBMAD(spine) , nor aBMD(total hip) were significantly associated with epilepsy, antiepileptic treatment, MECP2 mutation group, XCI, or vitamin D status. Low bone mass and small bones are evident in RTT, indicating an apparent low-bone-formation phenotype.