PMID- 23505553
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - Zoledronate effects on systemic and jaw osteopenias in ovariectomized 
      periostin-deficient mice.
PG  - e58726
LID - 10.1371/journal.pone.0058726 [doi]
LID - e58726
AB  - Osteoporosis and periodontal disease (PD) are frequently associated in the 
      elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. 
      Bisphosphonates improve alveolar bone loss but have also been associated with 
      osteonecrosis of the jaw (ONJ), particularly using oncological doses of 
      zoledronate. The effects and therapeutic margin of zoledronate on jaw bone 
      therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate 
      (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic 
      model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 
      microg/kg/month) and Zol 1W (100 microg/kg/week) for 3 months both significantly improved 
      femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone 
      volume in both OVX Postn(+/+) and Postn(-/-) (all p<0.01). Zol 1M and Zol 1W also 
      improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was 
      less efficient, particularly in Postn(-/-). Zol decreased osteoclast number and 
      bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn(-/-) 
      and Postn(+/+), both in the long bones and in deep jaw alveolar bone, without 
      differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation 
      nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance 
      between the root and the enamel of the incisor (DRI) remained high in Postn(-/-) 
      vs Postn(+/+) confirming latent inflammation and lack of crestal alveolar bone. 
      Zol 1W and Zol 1M decreased osteocyte numbers in Postn(-/-) and Postn(+/+) 
      mandible, and Zol 1W increased the number of empty lacunae in Postn(-/-), however 
      no areas of necrotic bone were observed. These results demonstrate that 
      zoledronate improves jaw osteopenia and suggest that in Postn(-/-) mice, 
      zoledronate is not sufficient to induce bone necrosis.
FAU - Bonnet, Nicolas
AU  - Bonnet N
AD  - Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva 
      University Hospital, Geneva, Switzerland. nicolas.bonnet@unige.ch
FAU - Lesclous, Philippe
AU  - Lesclous P
FAU - Saffar, Jean Louis
AU  - Saffar JL
FAU - Ferrari, Serge
AU  - Ferrari S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130307
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Diphosphonates)
RN  - 0 (Imidazoles)
RN  - 0 (Postn protein, mouse)
RN  - 6XC1PAD3KF (Zoledronic Acid)
SB  - IM
MH  - Animals
MH  - Bone Density/drug effects
MH  - Bone Density Conservation Agents/*administration & dosage
MH  - Bone Diseases, Metabolic/diagnosis/*drug therapy
MH  - Bone Remodeling/drug effects
MH  - Bone Resorption/drug therapy/pathology
MH  - Bone and Bones/diagnostic imaging/drug effects/pathology
MH  - Cell Adhesion Molecules/*deficiency
MH  - Diphosphonates/*administration & dosage
MH  - Female
MH  - Imidazoles/*administration & dosage
MH  - Jaw/*pathology
MH  - Mice
MH  - Mice, Knockout
MH  - *Ovariectomy
MH  - Tomography, X-Ray Computed
MH  - Zoledronic Acid
PMC - PMC3591374
COIS- Competing Interests: The authors have the following interests: Co-author Serge 
      Ferrari has declared a conflict of interest since he serves as an expert in 
      trials about ONJ cases in the US involving Novartis; however, he is not an 
      employee of this company nor is he directly remunerated by the company for this 
      expertise. There are no patents, products in development or marketed products to 
      declare. This does not alter the authors' adherence to all the PLOS ONE policies 
      on sharing data and materials.
EDAT- 2013/03/19 06:00
MHDA- 2013/09/07 06:00
PMCR- 2013/03/07
CRDT- 2013/03/19 06:00
PHST- 2012/11/21 00:00 [received]
PHST- 2013/02/05 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
PHST- 2013/03/07 00:00 [pmc-release]
AID - PONE-D-12-36472 [pii]
AID - 10.1371/journal.pone.0058726 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e58726. doi: 10.1371/journal.pone.0058726. Epub 2013 Mar 7.