Genetic Susceptibility Factors and Clinical Manifestations of Sickle Cell Bone Disease in Patients at the University of Nigeria Teaching Hospital, Enugu

Sickle cell disease causes a diverse spectrum of orthopaedic complications including avascular necrosis, dactylitis, pathological fractures, and chronic osteomyelitis, collectively termed sickle cell bone disease (SCBD). Nigeria carries the world's largest burden of sickle cell disease, yet orthopaedic manifestation characterisation linked to genetic polymorphisms remains poorly investigated in local populations. This analytical cross-sectional study examines the relationship between selected genetic susceptibility factors (alpha-thalassaemia co-inheritance, HbF levels, and beta-globin haplotype) and the clinical and radiological manifestations of sickle cell bone disease in patients attending the Comprehensive Sickle Cell Centre at University of Nigeria Teaching Hospital (UNTH), Enugu, South East Nigeria. One hundred and fifty HbSS patients and fifty HbSC patients will be enrolled. Clinical assessments for avascular necrosis, osteomyelitis, and spinal involvement will be performed alongside radiographic evaluation. Blood samples will be analysed for HbF levels and genetic co-inheritance markers. Logistic regression will identify genetic predictors of specific SCBD manifestations. The study hypothesises that low HbF levels and absence of alpha-thalassaemia co-inheritance correlate with higher orthopaedic complication rates. Findings will contribute to a precision medicine framework for SCBD management in Nigeria. Keywords: sickle cell bone disease, avascular necrosis, HbF, genetic susceptibility, Enugu.