title: Implications of high-dosage bisphosphonate treatment on bone tissue in the jaw and knee joint.
abstract: Bisphosphonates are bone antiresorptive agents traditionally used on a relatively large scale for treatment of bone metabolic diseases and on a smaller scale for bone metastasis treatment. A study on the effects of bisphosphonate treatment on healthy instead of diseased animals will give more insight into the basic mechanisms of bisphosphonates and their effects on different bone sites. We aimed to assess the effect of BP on the mouse knee and jaw joint. Three-month old female C57BL/6 mice were used (twenty-four and eighteen control and experimental group, respectively). At baseline and after treatment with zoledronic acid (ZA) for one, three or six months, we combined bone assessment via µCT and additional histology. Our results showed that, in the knee joint, ZA treatment increased TMD, bone volume, trabecular thickness but did not influence cortical thickness. In both control and ZA group, a higher trabecular TMD compared to cortical TMD was seen. Unseen in the knee joint, ZA treatment in the jaw joint resulted in bone-site specific changes in mineralization; a significant time-dependent higher TMD was evident in the subchondral bone compared to the most distal region of the condyle. MicroCT images revealed the presence of mineral in this region and histology showed that this region did not contain mature bone tissue but cartilage-like tissue. Our data indicate the possibility of site-specific negative side effects, i.e., disturbing normal mandibular development under the influence of bisphosphonate therapy.
authors.affiliation: Department of Oral Cell Biology & Functional Anatomy, Academic Center for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands, greetjerenders@gmail.com.
authors.forename: Greetje A P
authors.initials: GA
authors.lastname: Renders
authors.forename: Jenny A F
authors.initials: JA
authors.lastname: Vermeer
authors.forename: Pui-Ming
authors.initials: PM
authors.lastname: Leung
authors.forename: Freya
authors.initials: F
authors.lastname: Reynaert
authors.forename: Carla
authors.initials: C
authors.lastname: Prins
authors.forename: Geerling E J
authors.initials: GE
authors.lastname: Langenbach
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
mesh_terms: D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D007093:Imidazoles / Q000009:adverse effects*; D007568:Jaw / Q000000981:diagnostic imaging / Q000187:drug effects*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid