Vitamin D Deficiency and Avascular Necrosis in Patients With Sickle Cell Disease: A Retrospective Cohort Study

Introduction Sickle cell disease (SCD) is an inherited hemoglobinopathy with complex multi-systemic involvement. Avascular necrosis (AVN) is a devastating complication among patients with SCD. Vitamin D deficiency (VDD) is a common finding in SCD patients. However, there is a paucity of research that evaluates the potential role of VDD as a risk factor for AVN in patients with SCD. This study aimed to assess the association between VDD and AVN and determine the patterns of presentation, risk factors, diagnosis, and treatment of AVN in patients with SCD. Methods We conducted a retrospective cohort study of consecutive SCD patients diagnosed with VDD from January 2020 to December 2022 at Prince Sultan Medical Military City (PSMMC), Riyadh, Saudi Arabia. Inclusion criteria: (1) adults and children with confirmed SCD and (2) tested for VDD. We excluded patients who underwent bone marrow transplants. The associations were assessed using the chi-square test. Logistic regression was performed to control for confounding. Results The study included 711 eligible patients; 271 (38%) were children. VDD affected 301/711 (42.3%). VDD was noticed in 32.2% and 48.1% of children and adults, respectively. AVN was diagnosed in 127/711 (17.9%) patients. The mean age at AVN diagnosis was 30.9 ± 11 years. The most common presentation of AVN was chronic joint pain (> 95%). The most frequently affected joint was the hip (86%). The majority of patients (76.4%) were late in stage at diagnosis of AVN (III/IV). Patients with a history of VDD were significantly associated with a higher risk of AVN (p < 0.001). Using multivariate logistic regression, SCD patients with VDD have 9.79 times the odds of AVN compared with SCD patients without VDD (OR 9.79; 95% CI: 5.25 - 18.26). Other statistically significant risk factors for AVN included frequent vaso-occlusive crises, older age, history of acute chest syndrome, and high body mass index. Conclusion AVN is a significant cause of morbidity in our SCD cohort. Most of the patients had advanced AVN disease. VDD is an independent risk factor for the occurrence of AVN. Well-designed randomized trials are required to determine the effect of vitamin D supplementation in reducing AVN in patients with SCD.