Creatine Kinase as Biomarker in Osteogenesis Imperfecta

  • Patrizia D’EufemiaEmail author
  • Mauro Celli
  • Anna Zambrano
  • Roberto Finocchiaro
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)


Creatine kinase (CK) plays a storage and distribution role in cellular energetics. There are two mammalian CK cytosolic isoforms, the muscle type (CKm) and the brain type (CKb) that form homodimers or heterodimers as CKmm, CKmb, and CKbb. CKbb is present in a range of tissue, including the bone. Osteogenesis imperfecta (OI) is a heterogeneous group of heritable connective disorder causing bone fragility of varying severity. In most cases, the diagnosis is based on clinical and radiological data, but serum determination of marker bone formation and resorption may help for therapy decision. Actually, N-BPs are considered the current standard of care for treating OI since they potently inhibit bone resorption by suppressing the activity of osteoclasts.

In the past, clinical studies reported an increased serum CKbb in patients with genetic osteopetrosis (OPT) and in a patient with acquired OPT due to prolonged N-BP therapy. A recent report evidenced an increase of serum CKbb in children with OI type I during therapy with N-BPs probably reflecting suppression of osteoclast function. The hypothesis that osteoclasts could represent an important source of CKbb has been confirmed in a recent in vitro study, performed on rabbit-stimulated osteoclasts incubated in medium containing various N-BPs. This study confirmed that osteoclasts are the source of CK release from the bone and that this is an osteoclast apoptosis-related event.

Although until now no significant correlation has been found between serum CKbb and parameter of clinical outcome, it is likely that serum CKbb determination could help to evaluate risk condition due to oversuppression of osteoclast activity before the occurring of clinical evidence of pathological changes of bone density.


Creatine kinase Creatine kinase isoforms Osteogenesis imperfecta Collagen type I Osteoclast Osteoblast Bisphosphonates 

List of Abbreviation


Adenine nucleotide translocator


Analog of ATP


Bone mineral density




Creatine kinase


Brain-type creatine kinase


Muscle/brain-type creatine kinase


Muscle-type creatine kinase




Cr transporter


C-Terminal cross-linked telopeptide of collagen


Farnesyl diphosphate synthase


Glycolytic enzymes


Isopentenyl diphosphate


Nitrogen-containing bisphosphonates


C-Terminal cross-linked telopeptide of collagen I


Osteogenesis imperfecta


Oxidative phosphorylation






Poly(ADP-ribose) polymerase-1




C-Terminal propeptides of procollagen I


N-Terminal propeptides of procollagen I


Receptor activator of nuclear factor kB


Receptor activator of nuclear factor kB ligand


Tumor necrosis factor




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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Patrizia D’Eufemia
    • 1
    Email author
  • Mauro Celli
    • 1
  • Anna Zambrano
    • 1
  • Roberto Finocchiaro
    • 1
  1. 1.Department of Pediatrics “Sapienza”University of RomeRomeItaly

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