Evaluation of bone formation and resorption markers in children with Marfan syndrome

Introduction and Objective: Marfan Syndrome (MFS) is an autosomal dominant disorder that causes structural abnormalities in connective tissue due to mutations in the fibrilin-1 (FBN1) gene. FBN1 mutations can influence the skeletal system and bone metabolism by increasing Transforming Growth Factor-Beta (TGF-β1) levels. This study aimed to investigate bone-related biochemical tests, serum bone markers, and bone mineral densitometry values in children diagnosed with MFS and carrying an FBN1 mutation. Additionally, it sought to evaluate the fracture frequency in affected individuals and compare serum bone markers with those of a control group without known disease. Materials and Methods: This study included 29 children diagnosed with MFS and confirmed to carry an FBN1 mutation, as well as 34 healthy controls, all followed up at Akdeniz University Department of Pediatrics between January 2010 and June 2023. Retrospective data collection included bone-related biochemical tests and bone mineral density (BMD) measurements obtained via Dual-Energy X-ray Absorptiometry (DEXA), with height-adjusted Z-scores calculated. Prospectively, serum bone markers (Osteocalcin, Type 1 Collagen C-terminal Telopeptide [CTX], Procollagen Type 1 N-Terminal Propeptide [PINP], TGF-β1) were analyzed using the ELISA method. Results: In patients diagnosed with MFS, the mean height SDS is higher, and BMI is lower compared to the control group (p<0.001). There is no significant difference between the groups in terms of bone-related biochemical tests and serum bone markers, including osteocalcin and CTX. However, TGF-β1 and PINP levels are statistically significantly higher in the MFS group compared to the control group (p<0.001). The prevalence of serum 25OHD insufficiency in Marfan syndrome patients is 10.3% (3/29), while the deficiency rate is 20.6% (6/29). In our study, the DEXA results of 21 patients were analyzed, and height-adjusted correction, as recommended by Zemel et al., was applied. The mean L1-L4 vertebra HAZ score was calculated as -2.55, while the femoral neck HAZ score was -2.15. The mean age in the low BMD group, classified according to femoral neck HAZ scores, was statistically significantly higher than in the normal BMD group (p<0.037). In the low BMD group, defined based on the total L1-L4 vertebra score, CTX levels were statistically significantly higher compared to the normal BMD group (p<0.046). In our study group, only one patient had a history of trauma-related fracture. Conclusion: Our study is one of the first to comprehensively examine biomarkers related to bone health in pediatric MFS cases. However, the limited number of cases and the cross-sectional design of the study restrict definitive conclusions regarding fracture risk. It is recommended that bone health be regularly monitored in the long-term follow-up of patients with Marfan syndrome, and appropriate preventive measures be implemented. Keywords: Marfan Syndrome, Bone Mineral Density, DEXA, 25OHD, Osteocalcin, TGF-β1, PINP, CTX