title: Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy.
abstract: BACKGROUND
  Hypophosphatasia (HP) is characterized by a genetic defect in the tissue-nonspecific alkaline phosphatase (TNSALP) gene and predominantly an autosomal recessive trait. HP patients suffer from reduced bone mineralization. Biochemically, elevated concentrations of substrates of TNSALP, including pyridoxal-5'-phosphate and inorganic pyrophosphate occur in serum, tissues and urine. The latter has been associated with chronic inflammation and hyperprostaglandinism.
  
  
  METHODS
  We report on 2 affected children presenting with multifocal inflammatory bone lesions mimicking malignancy: A 6 years old girl with short stature had been treated with human growth hormone since 6 months. Then she started to complain about a painful swelling of her left cheek. MRI suggested a malignant bone lesion. Bone biopsy, however, revealed chronic inflammation. A bone scan showed a second rib lesion. Since biopsy was sterile, the descriptive diagnosis of chronic non-bacterial osteomyelitis (CNO) was established. The diagnostic tests related to growth failure were repeated and subsequent analyses demonstrated a molecular defect in the TNSALP gene. The second girl (10 years old) complained about back pain after she had fallen from her bike. X rays of her spine revealed compressions of 2 thoracic vertebrae. At first these were considered trauma related, however a bone scan did show an additional lesion in the right 4th rib. A biopsy of this rib revealed a sterile lympho- plasmocytoid osteomyelitis suggesting multifocal CNO. Further analyses did show a decreased TNSALP in leukocytes and elevated pyridoxal phosphate in plasma, suggesting a heterozygous carrier status of HP.
  
  
  CONCLUSIONS
  Chronic bone oedema in adult HP and chronic hyper-prostaglandinism in childhood HP do suggest that in some HP patients bone inflammation is present in conjunction with the metabolic defect. Sterile multifocal osteomyelitis could be demonstrated. Non-steroidal anti-inflammatory treatment achieved complete remission. These cases illustrate chronic inflammation of the bone as a new feature of HP.
authors.affiliation: Children's Hospital, University of Würzburg, Germany. Hermann.Girschick@mail.uni-wuerzburg.de
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Girschick
authors.forename: Etienne
authors.initials: E
authors.lastname: Mornet
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.forename: Peter
authors.initials: P
authors.lastname: Schneider
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D001707:Biopsy, Needle; D001774:Blood Chemical Analysis; D001859:Bone Neoplasms / Q000175:diagnosis*; D002113:Calcification, Physiologic / Q000502:physiology; D002648:Child; D002908:Chronic Disease; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis* / Q000188:drug therapy; D008279:Magnetic Resonance Imaging; D009288:Naproxen / Q000627:therapeutic use; D010019:Osteomyelitis / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D011453:Prostaglandins / Q000097:blood; D012008:Recurrence; D018570:Risk Assessment
chemical_list: D011453:Prostaglandins; D009288:Naproxen; D000469:Alkaline Phosphatase