Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

Background: Patients with Rett syndrome (RTT) are at risk of having low bone mass and low-energy fractures. Methods: We characterized bone metabolism by both bone formation and resorption markers in blood in a RTT population of 61 girls and women and 122 well-matched healthy controls. Levels of N-terminal propeptides of collagen type 1 (P1NP), C-terminal telopeptide cross links (CTX), osteocalcin (OC), and bone-specific alkaline phosphatase (B-ALP) were compared between RTT patients and controls in regression models adjusted for BMI, vitamin D status, volumetric bone mineral apparent density of the lumbar spine (vBMADspine), and femoral neck (vBMADneck). We examined biochemical bone marker levels overall and stratified to persons younger than age 25 y or equal to or older than age 25 y. Results: The RTT patients had reduced levels of all biochemical bone markers (P < 0.05), which remained significant in persons younger than 25 y (P ≤ 0.001) regarding P1NP, CTX, and OC. Bone marker levels were not significantly associated to methyl-CpG-binding protein 2 (MECP2) mutation group, walking ability, or previous low-energy fractures. Conclusion: Our findings of a low bone turnover state in girls with RTT suggest critical attention to medical treatment of low bone mass in young RTT patients