Bisphosphonate modulates morphological and mechanical properties in distraction osteogenesis through inhibition of bone resorption

Despite the general clinical acceptance of distraction osteogenesis and much attention to bone formation in this method, little is recognized about activated bone resorption in the regenerated bone. The purpose of this study was to demonstrate the simultaneously activated bone resorption with activa...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2006-09, Vol.39 (3), p.573-581
Main Authors: Takahashi, Mitsuhiko, Yukata, Kiminori, Matsui, Yoshito, Abbaspour, Aziz, Takata, Shinjiro, Yasui, Natsuo
Format: Article
Language:English
Subjects:
Absorptiometry, Photon
Animals
Biological and medical sciences
Bisphosphonate
Bone resorption
Bone Resorption - drug therapy
Bone Resorption - pathology
Bone strength
Bones, joints and connective tissue. Antiinflammatory agents
Calcification, Physiologic - drug effects
Diphosphonates - pharmacology
Distraction osteogenesis
Fundamental and applied biological sciences. Psychology
Head and neck surgery. Maxillofacial surgery. Dental surgery. Orthodontics
Male
Maxillofacial surgery. Dental surgery. Orthodontics
Medical sciences
Morphological modulation
Osteogenesis - drug effects
Pharmacology. Drug treatments
Rabbits
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Despite the general clinical acceptance of distraction osteogenesis and much attention to bone formation in this method, little is recognized about activated bone resorption in the regenerated bone. The purpose of this study was to demonstrate the simultaneously activated bone resorption with activated bone formation and to investigate the role and efficacy of bisphosphonate in distraction osteogenesis. Left tibiae of 54 immature rabbits were lengthened for 3 weeks at a rate of 0.7 mm/day after a 1-week lag. Regenerated bone was quantitatively investigated by radiographic bone density, bone histomorphometry, and three-point bending testing. Animals received either vehicle or nitrogen-containing bisphosphonate (N-BP), YM529/ONO5920 at doses of 0.4 mg/kg/w or 0.004 mg/kg/w for 6 weeks. Regenerated bone of the vehicle group showed a radiologically characteristic zone structure containing the osteopenic zones adjacent to the sclerotic zones. The regenerated bone of the 0.4-mg/kg/w group showed no osteopenic zones during the course and eventually became homogeneously radiodense. The bone volume corresponding to the osteopenic zone of this group was 5.6-fold greater compared with that of the vehicle group. The lengthened bone strength of this group was 3.3-fold greater in ultimate force than that of the vehicle group and equivalent to the contralateral tibia. The 0.004-mg/kg/w group had no substantial differences compared with the vehicle group, despite radiological enhancement of the mineralized front as well as somewhat delayed bone resorption. These results demonstrate that not only bone formation but also bone resorption is highly activated in the regenerated bone, implying high bone turnover. Sufficient N-BP caused a notable modulation in morphological properties of the regenerated bone through inhibition of highly activated bone resorption and eventually increased mechanical properties.
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2006.03.010