title: Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment.
abstract: BACKGROUND
  Creatine kinase (Ck) catalyzes the reversible transfer of high-energy phosphate groups between adenosine triphosphate and phosphocreatine. The brain isoform (Ckbb) is greatly induced in mature osteoclasts, playing an important role in bone-resorbing function during osteoclastogenesis. High Ckbb serum level has been found in patients with osteopetrosis and in patients with bisphosphonate (BP)-induced osteopetrosis. BPs are considered the treatment of choice for children with osteogenesis imperfecta (OI), acting as potent inhibitors of bone resorption by suppressing the activity of osteoclasts.
  
  
  METHODS
  We determined total serum Ck and isoform activity in 18 prepubertal children with type I OI, before and during treatment with the BP neridronate infusions.
  
  
  RESULTS
  Basal serum Ckbb levels were slightly elevated with respect to controls (mean ± SD = 3.0 ± 2.7 vs. 2.0 ± 2.2) and progressively increased after neridronate treatment (t0 vs. t4: mean ± SD = 3.0 ± 2.7 to 10.8 ± 8.1), with significant increment after first, second, and fourth infusions (P < 0.01). An inverse correlation was found between serum Ckbb and serum CTx at basal level.
  
  
  CONCLUSIONS
  Our results support previous observations that increased serum Ckbb reflects failure of osteoclasts or, at least, suppression of osteoclasts. Upon considering that BPs are long acting, this information could be useful to prevent the risk of overtreatment after long-term BP exposure in pediatric patients with OI.
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Patrizia
authors: P
authors: D'Eufemia
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Roberto
authors: R
authors: Finocchiaro
authors: Department of Orthopaedics and Traumatology, "Sapienza", University of Rome, Rome, Italy.
authors: Ciro
authors: C
authors: Villani
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Anna
authors: A
authors: Zambrano
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Valentina
authors: V
authors: Lodato
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Marta
authors: M
authors: Palombaro
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Enrico
authors: E
authors: Properzi
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: Mauro
authors: M
authors: Celli
mesh_terms: D001862:Bone Resorption; D002648:Child; D002675:Child, Preschool; D052276:Creatine Kinase, BB Form / Q000097:blood*; D003720:Densitometry; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010010:Osteoclasts / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000097:blood* / Q000188:drug therapy*; D012306:Risk
chemical_list: D004164:Diphosphonates; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; D052276:Creatine Kinase, BB Form