Osteoporosis in RETT Syndrome (OSRETT)

Osteoporosis in RETT Syndrome. Understanding the Mechanisms and Identification of Biomarkers.

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:

1. 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)
2. evaluation of the mineral density at the lumber spine using DEXA
3. measuring concentrations of osteoprotegerin and RANK-ligand

Study Overview

• Status: Completed
• Conditions: RETT Syndrome With Proven MECP2 Mutation
• Intervention / Treatment: Other: biological markers and evaluation of the mineral density at the lumber spine using DEXA

Detailed Description

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:

1. 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)
2. evaluation of the mineral density at the lumber spine using DEXA
3. measuring concentrations of osteoprotegerin and RANK-ligand

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bicêtre, France, 94275
    • Kremlin Bicêtre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• RETT syndrome
• MECP2 mutation

Exclusion Criteria:

• no identified MECP2 mutation
• history of drugs that interfere with bone metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: RETT patients	Other: biological markers and evaluation of the mineral density at the lumber spine using DEXA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
osteoporosis in RETT patients	Correlation between clinical/biological risk factors and mineral density and osteoporosis in RETT patients	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological Mechanisms of osteoporosis	RANK-ligand and osteoprotegerin concentrations	Day 0

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Agnès Linglart, MD, PhD, Kremlin Bicetre hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 10, 2009
• Primary Completion (ACTUAL): June 6, 2014
• Study Completion (ACTUAL): June 6, 2014

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (ESTIMATE): April 10, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 19, 2018
• Last Update Submitted That Met QC Criteria: March 16, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Osteoporosis; MECP2; RETT syndrome; RANK-ligand; osteoprotegerin
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Bone Diseases; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Bone Diseases, Metabolic; Syndrome; Osteoporosis; Rett Syndrome
• Other Study ID Numbers: P071230