title: PLGA-linked alendronate enhances bone repair in diaphysis defect model.
abstract: Alendronate (ALN) is known as an anti-resorptive drug for the treatment of osteoporosis. Recently, ALN was found to stimulate osteogenic differentiation in mesenchymal stem cells and enhance new bone formation in calvarial bone defects. Previous in vitro and in vivo studies found that the effective concentration of ALN was approximately 1-10   μm. In the present study, a poly (lactic-co-glycolic acid) (PLGA) cross-linked ALN (PLGA-ALN) with a short-term controlled-release property for local application to enhance bone repair was developed. An in vitro drug-release kinetic test showed that PLGA-ALN microspheres released an effective concentration (50-100 nm) of ALN for 9 days. The effect of PLGA-ALN on bone repair was tested in a rat femoral bone defect model. The biomechanical study results showed that the maximal strength, stiffness and energy absorption were significantly increased in the PLGA-ALN group compared with the PLGA group. The microstructure of the newly formed bone at the defect site was analysed using microcomputed tomography. The PLGA-ALN group significantly improved the trabecular bone volume at the defect site compared with the PLGA group. The fibril collagen and immunolocalized bone morphogenetic protein 2 were evident in the newly formed trabecular bone in the PLGA-ALN group. Local use of newly developed PLGA-ALN-enhanced bone repair was attributable to increasing bone matrix formation, which improved the ultrastructure of the newly formed bone and thus increased the biomechanical properties of the repaired bone. It is suggested that PLGA-ALN may be a potential bone graft substitute to enhance bone repair. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yao-Hsien
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Biomedical Science, Faculty of Biomedical Sciences Technology and Research, Sri Ramachandra University, Porur, Chennai, India.
authors.forename: Eswaramoorthy
authors.initials: E
authors.lastname: Rajalakshmanan
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Wang
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yin-Chi
authors.initials: YC
authors.lastname: Fu
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tzu-Lin
authors.initials: TL
authors.lastname: Tsai
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Je-Ken
authors.initials: JK
authors.lastname: Chang
authors.affiliation: Orthopedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Ho
mesh_terms: D019386:Alendronate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019386:Alendronate
keywords: alendronate (ALN); bone graft substitute; controlled release; femoral defect; osteogenesis; poly-lactic-co-glycolic acid (PLGA)