Osteoporosis in RETT Syndrome. Understanding the Mechanisms and Identification of Biomarkers.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 2
- 主要终点
- osteoporosis in RETT patients
研究概览
简要总结
Based on our clinical observations, many girls with RETT syndrome, a severe neuro-developmental encephalopathy, suffer from osteoporosis which can appear at a very early age (before age 10) and can lead to fractures, pain and a limitation in mobility. Few epidemiological studies have estimated the frequency of osteoporosis in girls with RETT syndrome and showed that they are more exposed then children with other neuro-developmental diseases with a same degree of neurological handicap. However, the mechanisms that lead to early osteoporosis in RETT syndrome remain unknown. Mutations in the MECP2 gene are found in 95% of RETT patients and preliminary experimental studies have shown that this can lead to abnormal expression of the gene that codes for osteoprotegerin, a protein implicated in bone remodelling by interacting with RANK-ligand.
In order to identify risk factors of osteoporosis in RETT syndrome and to understand the pathophysiological mechanisms the study protocol includes:
- Clinical evaluation of bone health (history of bone fractures, pain, nutritional status, pubertal stage, daily caloric/calcium intake, anti-epileptic drugs, walking ability, vitamin D satus)
- evaluation of the mineral density at the lumber spine using DEXA
- measuring concentrations of osteoprotegerin and RANK-ligand
详细描述
Based on our clinical observations, many girls with RETT syndrome, a severe neuro-developmental encephalopathy, suffer from osteoporosis which can appear at a very early age (before age 10) and can lead to fractures, pain and a limitation in mobility. Few epidemiological studies have estimated the frequency of osteoporosis in girls with RETT syndrome and showed that they are more exposed to osteoporosis then children with other neuro-developmental diseases with a same degree of neurological handicap. However, the mechanisms that lead to early osteoporosis in RETT syndrome remain unknown.
Mutations in the MECP2 gene are found in 95% of RETT patients. Preliminary experimental studies on the transcriptional consequences of MECP2 mutations showed that the expression of 13 genes were significantly dysregulated and one of them is the gene that codes for osteoprotegerin, a soluble receptor that binds to RANK-ligand. RANK-ligand is an osteoclastic differentiation factor expressed by osteoblasts.
In order to identify risk factors of osteoporosis in RETT syndrome and to understand the pathophysiological mechanisms the study protocol includes:
- Clinical evaluation of bone health (history of bone fractures, pain, nutritional status, pubertal stage, daily caloric/calcium intake, anti-epileptic drugs, walking ability, vitamin D status)
- evaluation of the mineral density at the lumber spine using DEXA
- measuring concentrations of osteoprotegerin and RANK-ligand
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 45 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •RETT syndrome
- •MECP2 mutation
排除标准
- •no identified MECP2 mutation
- •history of drugs that interfere with bone metabolism
研究组 & 干预措施
RETT patients
干预措施: biological markers and evaluation of the mineral density at the lumber spine using DEXA (Other)
结局指标
主要结局
osteoporosis in RETT patients
时间窗: Day 0
Correlation between clinical/biological risk factors and mineral density and osteoporosis in RETT patients
次要结局
- Biological Mechanisms of osteoporosis(Day 0)