title: Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.
abstract: This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention.
  
  
  
  The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period.
  
  
  
  This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups.
  
  
  
  Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged.
  
  
  
  This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy. patdeufemia@inwind.it.
authors: P
authors: P
authors: D'Eufemia
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: R
authors: R
authors: Finocchiaro
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: A
authors: A
authors: Zambrano
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: V
authors: V
authors: Lodato
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: L
authors: L
authors: Celli
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: S
authors: S
authors: Finocchiaro
authors: Department of Anatomic Histologic Forensic and Locomotor Apparatus Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: P
authors: P
authors: Persiani
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: A
authors: A
authors: Turchetti
authors: Department of Pediatrics, "Sapienza", University of Rome, Rome, Italy.
authors: M
authors: M
authors: Celli
mesh_terms: D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004796:Clinical Enzyme Tests / Q000379:methods; D003402:Creatine Kinase / Q000097:blood*; D004164:Diphosphonates / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008297:Male; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007527:Isoenzymes; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; D003402:Creatine Kinase
keywords: Bisphosphonates; Bone metabolism; Creatine kinase isoenzymes; Osteoclast; Osteogenesis imperfecta