A study of ischemic bone lesions in a cohort of patients with sickle cell disease

Background Sickle cell disease (SCD) is a genetic blood disorder characterized by mutated haemoglobin, leading to deformed erythrocytes that can cause severe pain, anaemia and organ damage. One of its complications, avascular necrosis of the bone (AVN), arises when blood supply to a bone is disrupted, resulting in bone tissue death and potential joint deformities. AVN often starts asymptomatic, then progresses leading to severe pain and reduced mobility, especially if the bone collapses. Unfortunately, AVN in SCD patients is frequently either asymptomatic or misdiagnosed, and current management guidelines are limited, particularly for non-femoral lesions. Objective The study is aimed at investigating non-femoral avascular necrosis (NF-AVN) in SCD patients. AVN primarily affects the femoral head due to recurrent ischemia- reperfusion injuries. Previous research highlighted the development of occult AVN also beyond the femur in sickle cell anaemia patients. This study expanded on the aforementioned topic including more patients and examining temporal progression. Methods The study included all SCD patients treated at the Centre for Hemoglobinopathies. Patients with at least one MRI were included, and a subgroup with multiple MRIs of the same area was analysed. Inclusion criteria encompassed regular follow-up in our centre and specific SCD genotypes. Exclusion criteria applied to patients without or unable to undergo an MRI, or those with only a femoral head lesion. The research design involved collecting data from previous MRI scans, followed by a double-blind image analysis to evaluate bone lesion progression over time. Clinical history, haematological, biochemical, treatment and socio-demographic data were recorded and analysed for correlations with AVN risk. The data were analysed using the Mitchell classification to assess different stages of AVN. Results In the first part of the study (retrospective) 73 patients were enrolled because they had at least one MRI. In the second (prospective) 14 were enrolled, for a duration of 1 year. 109 MRI were analysed. The research identified that higher haemoglobin levels increased the risk of NF-AVN. This could be due to increased blood viscosity associated with higher haemoglobin levels. Gender did not impact risk, but genotype did, with HbSS carriers facing the highest risk. Regarding the lesions progression, the probability of regression of NF- AVN decreases with age. Our study proposes a new classification system for bone lesions beyond the femoral head, based on the Mitchell classification. Lesions at earlier stages showed potential for reversibility, but at stage B, reversibility became contingent on various circumstances. Stages C and D were entirely irreversible. We recommend a screening program for SCD affected children, starting at an early age, to detect and intervene in lesions before they become irreversible. MRI was deemed crucial for early detection due to its sensitivity and minimal radiation exposure. Our study emphasized the need for revised care protocols and follow-up for SCD patients, especially in paediatrics, including analysis of non-femoral bone districts. This approach could lead to more accurate and personalized treatments. Conclusion The study highlighted the prevalence and evolution of non-femoral avascular necrosis in sickle cell disease patients and proposed a comprehensive screening program using MRI to detect and manage complications at an early stage, potentially improving treatment outcomes.