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Integrated Analysis of Bone Resorption and Formation Pathways Reveals Mechanisms of Skeletal Impairment in Children
Arhum Subhan Khan1, Zeeba Zaka-Ur-Rab1, Faaz Bin Razi2
1Department of Paediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India.
Introduction:
Bone health impairment is an important but underexplored complication in pediatric haemophilia. This study aimed to evaluate bone remodelling imbalance by integrating bone mineral density (BMD), osteoclastogenic markers, Wnt signalling inhibitors, and mineral metabolism parameters.
Methods:
A case-control study was conducted, including children with haemophilia not receiving routine factor prophylaxis and age-matched healthy controls. Lumbar spine BMD was assessed. Serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), sclerostin, and Dickkopf-1 (DKK1) were measured. The osteoclastogenic index (RANKL/OPG ratio) was calculated. Serum calcium, phosphorus, alkaline phosphatase (ALP), parathyroid hormone, and vitamin D levels were also analysed. Regression and receiver operating characteristic (ROC) analyses were performed.
Results:
Haemophilia children with high AJBR (22.55 ± 18.84) and not receiving routine prophylaxis exhibited significantly lower lumbar spine BMD than controls. RANKL levels and the osteoclastogenic index were significantly elevated, while OPG levels showed no significant change, indicating enhanced osteoclast activity. Sclerostin levels were significantly increased, whereas DKK1 showed a non-significant rise, suggesting suppression of Wnt-mediated bone formation. Calcium, phosphorus, and ALP levels were significantly reduced, reflecting impaired mineralisation. The osteoclastogenic index showed a significant negative association with BMD and demonstrated excellent diagnostic performance on ROC analysis.
Conclusion:
Bone loss in children with haemophilia with high AJBR and not receiving routine prophylaxis is characterised by increased bone resorption, decreased bone formation, and impaired mineralisation. The osteoclastogenic index may serve as a robust biomarker for early detection and risk stratification of skeletal complications.
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