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Osteomyelitis is a common pediatric musculoskeletal infection. This infection can weaken the normal bone structure, resulting in the risk of a pathologic fracture. The purpose of this study was to evaluate the risk factors for pathologic fracture in children with Staphylococcus aureus osteomyelitis.Seventeen children who were treated for a pathologic long-bone fracture secondary to Staphylococcus aureus osteomyelitis between January 2001 and January 2009 at a tertiary-care pediatric hospital were identified. These patients were compared with a control group consisting of forty-nine children with Staphylococcus aureus osteomyelitis without a fracture who were matched for age, sex, and methicillin susceptibility. A retrospective review of the clinical records, magnetic resonance imaging (MRI) studies, and microbiologic findings was performed.Patients who developed a fracture presented with osteomyelitis at a mean age of 8.8 years (range, two to seventeen years). Fifteen of the seventeen patients had methicillin-resistant Staphylococcus aureus (MRSA) isolates, and two had methicillin-susceptible Staphylococcus aureus (MSSA). The mean time from disease onset to fracture was 72.1 days (range, twenty to 150 days). The duration of hospitalization, number of surgical procedures, duration of antibiotic treatment, and total number of complications differed significantly between the two groups. MRI studies at the time of admission demonstrated a significantly greater prevalence of subperiosteal abscess and greater circumferential size of such an abscess in the patients with a fracture. A sharp zone of abnormally diminished enhancement of the marrow was also more common in these patients. The USA300-0114 pulsotype was more commonly associated with an elevated likelihood of fracture.Staphylococcus aureus osteomyelitis is a serious infection that may predispose children to pathologic fractures. Protected weight-bearing and activity restriction are recommended in children with Staphylococcus aureus osteomyelitis who have the risk factors demonstrated in this study.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.