Osteonecrosis of the femoral head (OFH) in sickle-cell disease (SCD) has a prevalence of 6.8% on plain radiography in patients 10–24 years as reported by the Cooperative Study of SCD (CSSCD)(1). Risk factors of frequent vaso-occlusive crises (VOC) and elevated hematocrit were identified. Patients with HbSS and alpha thalassemia trait had the highest prevalence of OFH. We screened for OFH in 257 patients with SCD 10–21 years by plain radiography. We observed a prevalence of 12.4%(32 of 257) for all genotypes, SS/Sb0 thalassemia: 14.2%(26 of 182) and SC: 9.2%(6 of 65). Bilateral disease occurred in 56%(18/32) of patients. Risk factors identified by univariate analysis for patients with SS and Sb0 thalassemia included age (P 5 0.0001), male gender (P 5 0.02), decreased white blood cell count (P 5 0.02), increased hematocrit (P 5 0.02), reduced LDH (P 5 0.0003), elevated creatinine (P 5 0.037), and hydroxyurea treatment (0.009). Multivariate logistic regression analysis showed independent associations with OFH for hydroxyurea therapy [odds ratio (OR) 3.1, 95% confidence interval (CI): 1.17, 8.41, P 5 0.022], gender (OR 3.1, 95% CI: 1.05, 9.02, P 5 0.04, and age (OR 1.3, 95% CI: 1.07, 1.56, P 5 0.008). The overall prevalence of 12.4% is 1.8-fold higher than that reported by the CSSCD and that for SS and Sb0 thalassemia is 2.4-fold higher. Osteonecrosis of the femoral head (OFH) is a common and debilitating complication of SCD with highest prevalence in adults with Hb SS and co-existent alpha thalassemia trait as reported by the Cooperative Study of SCD (CSSCD). A report on the natural history of untreated symptomatic OFH in adult SCD demonstrated progression to collapse of the femoral head in 87% of patients within 5 years of diagnosis and the eventual need for arthroplasty in patients with advanced disease [2]. Bilateral disease is common and may occur in 40–91% of patients [3, 4]. The study reported herein screened for OFH in patients with SCD ages 10–21 years old by plain radiography as part of yearly health assessments and found an unexpectedly high prevalence at a single academic institution. The cohort of 257 subjects screened represents 83% of the 310 patients with SCD age 10–21 years who were seen from 2005 to 2010. OFH was diagnosed in 32 patients (SS: 25, SC: 6, Sb0 thalassemia: 1) The prevalence for all genotypes is 12.4%(32/257); for HbSS and HbSb0 thalassemia, prevalence is 14.2%(26/182) and HbSC 9.2%(6/65). Bilateral disease occurred in 56%(18/32) of patients, that is, 50 of the 64 hips were affected. The 50 affected hips were staged by the Steinberg method [5] and classified as Stage 1: 6 hips, Stage II: 26 hips, Stage III: 6 hips, Stage IV: 8 hips, Stage V: 2 hips, and Stage VI: 2 hips. Ten of 32 patients with OFH had symptomatic hip pain of which five required surgical procedures during the study period. Three HbSS patients had arthroplasty at ages 17, 19, and 20 years. Two patients, one HbSS and one HbSC, had core decompression at ages 13 and 15 years, respectively. All symptomatic patients had Steinberg Stage III or higher in the symptomatic hip. The clinical and laboratory parameters of study subjects with HbSS and HbSb0 thalassemia are described in Table I. Analysis was confined to these genotypes, because they account for the majority of patients with OFH (26 of 32 patients). Additionally, 46%(83 of 182) of the HbSS and HbSb0 thalassemia patients were treated with hydroxyurea and inclusion of HbSC patients would affect analysis of hydroxyurea effect on laboratory parameters. Univariate analysis showed that subjects with OFH were significantly older, more likely to be male, have …