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Creatine Kinase as Biomarker in Osteogenesis Imperfecta

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

Abstract

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.

Keywords

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

List of Abbreviation

ANT

Adenine nucleotide translocator

Apppl

Analog of ATP

BMD

Bone mineral density

BPs

Bisphosphonates

CK

Creatine kinase

CKbb

Brain-type creatine kinase

CKmb

Muscle/brain-type creatine kinase

CKmm

Muscle-type creatine kinase

Cr

Creatine

CRT

Cr transporter

CTx

C-Terminal cross-linked telopeptide of collagen

FPPS

Farnesyl diphosphate synthase

G

Glycolytic enzymes

IPP

Isopentenyl diphosphate

N-BPs

Nitrogen-containing bisphosphonates

NTx

C-Terminal cross-linked telopeptide of collagen I

OI

Osteogenesis imperfecta

OP

Oxidative phosphorylation

OPG

Osteoprotegerin

OPT

Osteopetrosis

PARP-1

Poly(ADP-ribose) polymerase-1

PCr

Phosphocreatine

PICP

C-Terminal propeptides of procollagen I

PINP

N-Terminal propeptides of procollagen I

RANK

Receptor activator of nuclear factor kB

RANKL

Receptor activator of nuclear factor kB ligand

TNF

Tumor necrosis factor

V-ATPase

Vacuolar-ATPase

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

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

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