OBJECTIVE: Osteonecrosis (ON) is a debilitating complication of cancer treatment in children and is usually associated with systemic steroid therapy. Defects of coagulation may be important in the pathogenesis of ON. This study evaluated the prevalence of factor V Leiden (FVL, 1691G-->A), the most common inherited thrombophilic state, the prothrombin 20210G-->A polymorphism, and the thermolabile methylene tetrahydrofolate reductase (MTHFR, 677C-->T) variant in a group of children in whom ON developed during or after treatment for cancer. STUDY DESIGN: Children in whom ON developed during cancer treatment at St Jude Children's Research Hospital were studied (n = 24). Genomic DNA was isolated, and polymerase chain reaction was performed to identify the FVL, prothrombin 20210, and thermolabile MTHFR mutations. RESULTS: Sixteen of 24 patients had acute lymphoblastic leukemia. The mean age at ON diagnosis was 14.4 +/- 3. 7 years. The mean interval between cancer diagnosis and ON diagnosis was 27 +/- 21 months. Twenty-two patients had received steroids for a mean duration of 24 +/- 15 weeks before having development of ON. No patient had a history of thrombosis. Five (21%) patients had a family history of thrombosis. Genetic analysis revealed 0 (0%) of 24 FVL, 1 (4.5%) of 22 prothrombin 20210, and 3 (13.6%) of 22 thermolabile MTHFR. None of these mutation frequencies was significantly different from our control frequencies or published values. CONCLUSIONS: Although procoagulant abnormalities in general and FVL in particular have been detected in a significant number of patients with ON of the jaw and Legg-Perthes disease, we did not identify an increased prevalence of FVL or other hypercoagulable state mutations in a cohort of children with ON that developed during or after treatment for a variety of cancers.
OBJECTIVE:Osteonecrosis (ON) is a debilitating complication of cancer treatment in children and is usually associated with systemic steroid therapy. Defects of coagulation may be important in the pathogenesis of ON. This study evaluated the prevalence of factor V Leiden (FVL, 1691G-->A), the most common inherited thrombophilic state, the prothrombin 20210G-->A polymorphism, and the thermolabile methylene tetrahydrofolate reductase (MTHFR, 677C-->T) variant in a group of children in whom ON developed during or after treatment for cancer. STUDY DESIGN:Children in whom ON developed during cancer treatment at St Jude Children's Research Hospital were studied (n = 24). Genomic DNA was isolated, and polymerase chain reaction was performed to identify the FVL, prothrombin 20210, and thermolabile MTHFR mutations. RESULTS: Sixteen of 24 patients had acute lymphoblastic leukemia. The mean age at ON diagnosis was 14.4 +/- 3. 7 years. The mean interval between cancer diagnosis and ON diagnosis was 27 +/- 21 months. Twenty-two patients had received steroids for a mean duration of 24 +/- 15 weeks before having development of ON. No patient had a history of thrombosis. Five (21%) patients had a family history of thrombosis. Genetic analysis revealed 0 (0%) of 24 FVL, 1 (4.5%) of 22 prothrombin 20210, and 3 (13.6%) of 22 thermolabile MTHFR. None of these mutation frequencies was significantly different from our control frequencies or published values. CONCLUSIONS: Although procoagulant abnormalities in general and FVL in particular have been detected in a significant number of patients with ON of the jaw and Legg-Perthes disease, we did not identify an increased prevalence of FVL or other hypercoagulable state mutations in a cohort of children with ON that developed during or after treatment for a variety of cancers.
Authors: Marios G Lykissas; Ioannis D Gelalis; Ioannis P Kostas-Agnantis; Georgios Vozonelos; Anastasios V Korompilias Journal: Orthop Rev (Pavia) Date: 2012-05-29