title: Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits.
abstract: The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics.
authors.affiliation: Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.|Institute of Orthopaedics, Xijing hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Da
authors.initials: D
authors.lastname: Jing
authors.affiliation: Department of orthopaedics, the Fifth Hospital of Harbin, Harbin, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Institute of Orthopaedics, Xijing hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, PLA 302 hospital, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
authors.forename: Erping
authors.initials: E
authors.lastname: Luo
authors.affiliation: Institute of Orthopaedics, Xijing hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Meng
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage; D007093:Imidazoles / Q000008:administration & dosage*; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: C525718:BMP2 protein, human; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D015718:Fibrin Tissue Adhesive; D007093:Imidazoles; D011994:Recombinant Proteins; D000077211:Zoledronic Acid