title: Bone-site-specific responses to zoledronic acid.
abstract: OBJECTIVE
  Bisphosphonates are widely used to treat bone diseases such as osteoporosis. However, they may cause osteonecrosis of the jaw. Here, we investigated whether in vivo exposure to bisphosphonates has a different effect on long bone and jaw osteoclasts, and on the turnover of these different bones.
  
  
  METHODS
  Zoledronic acid (0.5 mg kg-1weekly) was administered intraperitoneally to 3-month-old female mice for up to 6 months. The effects on the number of osteoclasts, bone mineralization and bone formation were measured in the long bones and in the jaw.
  
  
  RESULTS
  Long-term treatment with zoledronic acid reduced the number of jaw bone marrow cells, without affecting the number of long bone marrow cells. Zoledronic acid treatment did not affect the number of osteoclasts in vivo. Yet, the bisphosphonate increased bone volume and mineral density of both long bone and jaw. Interestingly, 6 months of treatment suppressed bone formation in the long bones without affecting the jaw. Unexpectedly, we showed that bisphosphonates can cause molar root resorption, mediated by active osteoclasts.
  
  
  CONCLUSIONS
  Our findings provide more insight into bone-site-specific effects of bisphosphonates and into the aetiology of osteonecrosis of the jaw. We demonstrated that bisphosphonates can stimulate osteoclast activity at the molar roots.
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaf
authors.initials: J
authors.lastname: Vermeer
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gap
authors.initials: G
authors.lastname: Renders
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van Duin
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Idc
authors.initials: I
authors.lastname: Jansen
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: L F
authors.initials: LF
authors.lastname: Bakker
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Kroon
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: T J
authors.initials: TJ
authors.lastname: de Vries
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Everts
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D018483:Diaphyses / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006811:Humerus / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007568:Jaw / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects*; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: bisphosphonates; bone remodelling; jaw; osteoclasts; osteonecrosis