title: Alterations of mass density and 3D osteocyte lacunar properties in bisphosphonate-related osteonecrotic human jaw bone, a synchrotron µCT study.
abstract: Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for treating osteoporosis or cancer, is a severe and most often irreversible side effect whose underlying pathophysiological mechanisms remain largely unknown. Osteocytes are involved in bone remodeling and mineralization where they orchestrate the delicate equilibrium between osteoclast and osteoblast activity and through the active process called osteocytic osteolysis. Here, we hypothesized that (i) changes of the mineralized tissue matrix play a substantial role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is altered in BRONJ. Synchrotron µCT with phase contrast is an appropriate tool for assessing both the 3D morphology of the osteocyte lacunae and the bone matrix mass density. Here, we used this technique to investigate the mass density distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in human bone samples from the jaw, femur and tibia. First, we compared healthy human jaw bone to human tibia and femur in order to assess the specific differences and address potential explanations of why the jaw bone is exclusively targeted by the necrosis as a side effect of BP treatment. Second, we investigated the differences between BRONJ and control jaw bone samples to detect potential differences which could aid an improved understanding of the course of BRONJ. We found that the apparent mass density of jaw bone was significantly smaller compared to that of tibia, consistent with a higher bone turnover in the jaw bone. The variance of the lacunar volume distribution was significantly different depending on the anatomical site. The comparison between BRONJ and control jaw specimens revealed no significant increase in mineralization after BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ group compared to the control jaw. Interestingly, the osteocyte-lacunar volume distribution was not altered after BP treatment.
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France ; Berlin-Brandenburg School for Regenerative Therapies & Julius Wolff Institut, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hesse
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France ; Université de Lyon, CREATIS, CNRS UMR5220, INSA-Lyon, Lyon, France.
authors.forename: Max
authors.initials: M
authors.lastname: Langer
authors.affiliation: Berlin-Brandenburg School for Regenerative Therapies & Julius Wolff Institut, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Varga
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France ; Université de Lyon, CREATIS, CNRS UMR5220, INSA-Lyon, Lyon, France ; Centre for Image Analysis and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pacureanu
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France ; Université de Lyon, CREATIS, CNRS UMR5220, INSA-Lyon, Lyon, France.
authors.forename: Pei
authors.initials: P
authors.lastname: Dong
authors.affiliation: Berlin-Brandenburg School for Regenerative Therapies & Julius Wolff Institut, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schrof
authors.affiliation: Berlin-Brandenburg School for Regenerative Therapies & Julius Wolff Institut, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Männicke
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France.
authors.forename: Heikki
authors.initials: H
authors.lastname: Suhonen
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France ; Université de Lyon, CREATIS, CNRS UMR5220, INSA-Lyon, Lyon, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Olivier
authors.affiliation: Klinik für Mund-, Kiefer- und Gesichtschirurgie, Klinikum Bremerhaven-Reinkenheide, Kiel, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Maurer
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Galateia J
authors.initials: GJ
authors.lastname: Kazakia
authors.affiliation: Berlin-Brandenburg School for Regenerative Therapies & Julius Wolff Institut, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Raum
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France ; Université de Lyon, CREATIS, CNRS UMR5220, INSA-Lyon, Lyon, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Peyrin
mesh_terms: D000704:Analysis of Variance; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology*; D015519:Bone Density / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D010011:Osteocytes / Q000000981:diagnostic imaging*; D017356:Synchrotrons; D055114:X-Ray Microtomography