title: 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.
authors.affiliation: Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan. m-kimura@oo.em-net.ne.jp
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kimura
authors.forename: Ken
authors.initials: K
authors.lastname: Miyazawa
authors.forename: Masako
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Hatsuhiko
authors.initials: H
authors.lastname: Maeda
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kameyama
authors.forename: Shigemi
authors.initials: S
authors.lastname: Goto
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000188:drug therapy / Q000473:pathology; D002452:Cell Count; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D020868:Gene Silencing; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008335:Mandibular Condyle / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010001:Osteitis Deformans; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D053244:Osteoprotegerin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007527:Isoenzymes; D053244:Osteoprotegerin; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase