PMID- 19450226
OWN - NLM
STAT- MEDLINE
DCOM- 20090626
LR  - 20220321
IS  - 1567-2018 (Print)
IS  - 1567-2018 (Linking)
VI  - 6
IP  - 2
DP  - 2009 Apr
TI  - Use of gastrointestinal proton pump inhibitors to regulate osteoclast-mediated 
      resorption of calcium phosphate cements in vivo.
PG  - 192-8
AB  - Osteoclasts degrade bone through the creation of an enclosed, acidic 
      extracellular microenvironment adjacent to the bone surface. Membrane bound 
      proton pumps in the osteoclast cell membrane function to create this acidified 
      environment. Accordingly, this H(+) ion transport mechanism provides a potential 
      target for a specific class of drugs, proton pump inhibitors (PPI), with a view 
      to controlling osteoclast mediated bone resorption. Self setting calcium 
      phosphate cements are common bone graft materials that are degraded by 
      osteoclastic activity. We have already shown that incorporation of bafilomycin, a 
      non-regulated PPI, within these cements prevents or delays osteoclast mediated 
      resorption of the cement. We demonstrate here that two regulated proton pump 
      inhibitors, Pantaprazole and Omeprazole, currently used clinically to treat 
      gastroesophageal reflux disorders, are effective in inhibiting osteoclast 
      mediated resorption in-vivo when delivered to a bony defect in self setting 
      calcium phosphate cements. As determined by qualitative histology, Pantaprazole 
      at a dose of 0.5mg/ml produced a delay in osteoclast resorption whilst this 
      effect was not as evident using Omeprazole at an equivalent dose, but higher 
      doses of Omeprazole (40mg/ml) did delay cement resorption. These data 
      demonstrate, for the first time, the functional effect of blocking the H(+)/K(+) 
      ATPase pump in-vivo on the capacity of osteoclasts to resorb bone and the 
      potential of this strategy to modulate osteoclast mediated resorption of calcium 
      phosphate biomaterials.
FAU - Sheraly, A R
AU  - Sheraly AR
AD  - Institute of Biomaterials and Biomedical Engineering, University of Toronto, 
      Canada.
FAU - Lickorish, D
AU  - Lickorish D
FAU - Sarraf, F
AU  - Sarraf F
FAU - Davies, J E
AU  - Davies JE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Drug Deliv
JT  - Current drug delivery
JID - 101208455
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Bone Cements)
RN  - 0 (Calcium Phosphates)
RN  - 0 (Isoenzymes)
RN  - 0 (Proton Pump Inhibitors)
RN  - D8TST4O562 (Pantoprazole)
RN  - EC 3.1.3.2 (Acid Phosphatase)
RN  - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/administration & 
      dosage/pharmacology/therapeutic use
MH  - Acid Phosphatase/metabolism
MH  - Animals
MH  - Bone Cements/chemistry/*metabolism
MH  - Bone Resorption/*prevention & control
MH  - Calcium Phosphates/chemistry/*metabolism
MH  - Femur/cytology/metabolism/surgery
MH  - Isoenzymes/metabolism
MH  - Male
MH  - Omeprazole/administration & dosage/pharmacology/therapeutic use
MH  - Osteoblasts/cytology/metabolism
MH  - Osteoclasts/cytology/*drug effects/metabolism
MH  - Pantoprazole
MH  - Proton Pump Inhibitors/*administration & dosage/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Tartrate-Resistant Acid Phosphatase
EDAT- 2009/05/20 09:00
MHDA- 2009/06/27 09:00
CRDT- 2009/05/20 09:00
PHST- 2009/05/20 09:00 [entrez]
PHST- 2009/05/20 09:00 [pubmed]
PHST- 2009/06/27 09:00 [medline]
AID - 10.2174/156720109787846225 [doi]
PST - ppublish
SO  - Curr Drug Deliv. 2009 Apr;6(2):192-8. doi: 10.2174/156720109787846225.