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Bisphosphonate treatment increases the size of the mandibular condyle and normalizes growth of the mandibular ramus in osteoprotegerin-deficient mice.

Abstract
Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. OPG-deficient (OPG-/-) mice develop severe osteoporosis caused by significant enhancement of bone resorption by osteoclasts. We investigated the effect of administering bisphosphonate on mandibular growth and development in OPG-/- mice. Eight-week-old male OPG-/- mice and wild-type (WT) mice were administered bisphosphonate (1.25 mg/kg body weight) intraperitoneally once every 3 days for 30 days. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG-/- mice with bisphosphonate than in those without bisphosphonate. The volume of the whole condyle and the mandibular length in OPG-/- mice without bisphosphonate were significantly smaller than in WT mice without bisphosphonate. Bisphosphonate treatment of the OPG-/- mice resulted in an increase in the volume of the mandibular condyle and mandibular ramus length. In fact, the mandibular ramus length in OPG-/- mice with bisphosphonate was similar to the length in WT mice without bisphosphonate. Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. In conclusion, bisphosphonate treatment results in an increase in mandibular condylar dimensions and normalization of mandibular ramus growth.
AuthorsMasakazu Kimura, Ken Miyazawa, Masako Tabuchi, Hatsuhiko Maeda, Yoichiro Kameyama, Shigemi Goto
JournalCalcified tissue international (Calcif Tissue Int) Vol. 82 Issue 2 Pg. 137-47 (Feb 2008) ISSN: 0171-967X [Print] United States
PMID18183447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Bone Density Conservation Agents
  • Diphosphonates
  • Isoenzymes
  • Osteoprotegerin
  • Osteocalcin
  • Alkaline Phosphatase
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
Topics
  • Acid Phosphatase (blood)
  • Alkaline Phosphatase (blood)
  • Animals
  • Biomarkers (blood)
  • Bone Density Conservation Agents (pharmacology)
  • Bone Resorption (drug therapy, pathology)
  • Cell Count
  • Diphosphonates (pharmacology)
  • Disease Models, Animal
  • Gene Silencing
  • Injections, Intraperitoneal
  • Isoenzymes (blood)
  • Male
  • Mandibular Condyle (drug effects, growth & development, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteitis Deformans
  • Osteocalcin (blood)
  • Osteoclasts (drug effects, enzymology, pathology)
  • Osteogenesis (drug effects, physiology)
  • Osteoprotegerin (drug effects, genetics, metabolism)
  • Tartrate-Resistant Acid Phosphatase

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