Bone Markers in Rett Syndrome

  • Gitte RoendeEmail author
  • Jens-Erik Beck Jensen
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)


Rett syndrome (RTT) is a severe neurodevelopmental disease affecting primarily girls because of a mutation of the gene methyl-CPG-binding protein 2, MECP2, located at the X chromosome. The hallmarks of RTT are global developmental delay, regression of mile stones as partial or complete loss of purposeful hand skills and acquired spoken language/babbling, gait abnormalities, and stereotypic hand movements. Girls with RTT are often growth retarded, have low bone mass, and increased occurrence of low-energy fractures. Recent studies of biochemical bone markers, e.g., osteocalcin, bone-specific alkaline phosphatase, N-terminal propeptides of collagen type 1, and C-terminal telopeptide (crosslinks), have shown reduced bone formation in the context of reduced/normal bone resorption in RTT patients compared to sex-, age-, and pubertal-matched healthy controls. This deviation of growth and bone formation is apparent from early age but without association to low bone mass or low-energy fractures. As for healthy children, patients with RTT have higher levels of bone markers in early childhood and prepubertal years followed by an overall decrease through puberty and by age. It is unknown whether there is a slight increase in biochemical bone markers during early-mid puberty. Patients with RTT do not have skewed levels of sex hormones, growth hormones, or thyroid hormones. Vitamin D levels are often in the range of insufficiency. No association to specific MECP2 mutations has been reported, but it is possible that MECP2 exerts a general influence on growth and bone formation. However, the specific relation to the osteoblast function and activity and the interplay with the osteoclasts remain to be elucidated. In support of a low bone turnover, phenotype in RTT is the result from a histomorphometric study of bone biopsies in RTT showing reduced bone volume and low bone formation rate. Studies of MECP2 null mice also report abnormal bone development with reduced osteoblast number, osteoblast dysmorphology, growth plate abnormalities, reduced bone volume, and reduced bone strength. As this deviation of bone development is potentially reversible in MECP2 null mice, it is important to continue research of bone metabolism in order to optimize possibilities of prevention and treatment of bone pathology in RTT.


Rett syndrome Methyl-CPG-binding protein 2 Bone mass Growth Bone formation Bone resorption N-terminal propeptides of collagen type 1 C-terminal telopeptide crosslinks Osteocalcin Bone-specific alkaline phosphatase 

List of Abbreviations


Bone-specific alkaline phosphatase


C-terminal telopeptide crosslinks


Deoxyribonucleic acid


Dual energy X-ray absorptiometry


Growth hormone


The gene methyl-CPG-binding protein 2


The protein methyl-CPG-binding protein 2




Type 1 procollagen carboxyterminal propeptide


N-terminal propeptides of collagen type 1


Parathyroid hormone


Ribonucleic acid


Rett syndrome

TSH T3 and T4

Thyroid hormones

Vitamin D

25-Hydroxy vitamin D2 and D3


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Department of PediatricsZealand University Hospital, Roskilde HospitalRoskildeDenmark
  2. 2.Department of EndocrinologyCopenhagen University Hospital, Hvidovre HospitalHvidovreDenmark

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