title: Controlled delivery of zoledronate improved bone formation locally in vivo.
abstract: Bisphosphonates (BPs) have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA) as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol) into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively) than control and low-dose Zol (3 µg PLGA-Zol; p<0.05). Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation.
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Gou
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Aiyuan
authors.initials: A
authors.lastname: Wang
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Xupeng
authors.initials: X
authors.lastname: Gao
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xu
authors.affiliation: Instistute of Orthopaedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Shibi
authors.initials: S
authors.lastname: Lu
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001842:Bone and Bones / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations; D004164:Diphosphonates / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D007093:Imidazoles / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D000071681:Tartrate-Resistant Acid Phosphatase; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D003692:Delayed-Action Preparations; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D007527:Isoenzymes; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase