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A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.
Osteoporos Int. 2016 Feb; 27(2):757-67.OI

Abstract

The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs.

INTRODUCTION

The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures.

METHODS

We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots.

RESULTS

Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin.

CONCLUSIONS

CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.

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Authors+Show Affiliations

Tan J
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
Fu X
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
Sun CG
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
Liu C
Department of Radiology, Peking University Third Hospital, Beijing, 100191, China.
Zhang XH
Department of Pharmacology, Peking University Third Hospital, Beijing, 100191, China.
Cui YY
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
Guo Q
Department of Neurology, Peking University Third Hospital, Beijing, 100191, China.
Ma T
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
Wang H
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
Du GH
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
Yin X
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
Liu ZJ
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
Leng HJ
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
Xu YS
Department of Neurology, Peking University Third Hospital, Beijing, 100191, China.
Song CL
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China. schl@bjmu.edu.cn. Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China. schl@bjmu.edu.cn.

MeSH

Absorptiometry, PhotonAnimalsBone DensityBone Morphogenetic Protein 2Chemistry, PhysicalDrug CombinationsDrug Delivery SystemsDrug Evaluation, PreclinicalFemaleHydrogel, Polyethylene Glycol DimethacrylateInjections, SpinalLumbar VertebraeMicroscopy, Electron, ScanningOsteogenesisOsteoporosisOvariectomyPoloxamerRadiography, InterventionalRheologySimvastatinSwineSwine, MiniatureTomography, X-Ray ComputedVascular Endothelial Growth Factor A

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26223190

Citation

Tan, J, et al. "A Single CT-guided Percutaneous Intraosseous Injection of Thermosensitive Simvastatin/poloxamer 407 Hydrogel Enhances Vertebral Bone Formation in Ovariectomized Minipigs." Osteoporosis International : a Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, vol. 27, no. 2, 2016, pp. 757-67.
Tan J, Fu X, Sun CG, et al. A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs. Osteoporos Int. 2016;27(2):757-67.
Tan, J., Fu, X., Sun, C. G., Liu, C., Zhang, X. H., Cui, Y. Y., Guo, Q., Ma, T., Wang, H., Du, G. H., Yin, X., Liu, Z. J., Leng, H. J., Xu, Y. S., & Song, C. L. (2016). A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs. Osteoporosis International : a Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 27(2), 757-67. https://doi.org/10.1007/s00198-015-3230-y
Tan J, et al. A Single CT-guided Percutaneous Intraosseous Injection of Thermosensitive Simvastatin/poloxamer 407 Hydrogel Enhances Vertebral Bone Formation in Ovariectomized Minipigs. Osteoporos Int. 2016;27(2):757-67. PubMed PMID: 26223190.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs. AU - Tan,J, AU - Fu,X, AU - Sun,C G, AU - Liu,C, AU - Zhang,X H, AU - Cui,Y Y, AU - Guo,Q, AU - Ma,T, AU - Wang,H, AU - Du,G H, AU - Yin,X, AU - Liu,Z J, AU - Leng,H J, AU - Xu,Y S, AU - Song,C L, Y1 - 2015/07/30/ PY - 2015/01/15/received PY - 2015/07/01/accepted PY - 2015/7/31/entrez PY - 2015/8/1/pubmed PY - 2016/12/15/medline KW - Local treatment KW - Osteoporosis KW - Percutaneous intraosseous injection KW - Poloxamer 407 hydrogel KW - Statins SP - 757 EP - 67 JF - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA JO - Osteoporos Int VL - 27 IS - 2 N2 - UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2. SN - 1433-2965 UR - https://www.unboundmedicine.com/medline/citation/26223190/A_single_CT_guided_percutaneous_intraosseous_injection_of_thermosensitive_simvastatin/poloxamer_407_hydrogel_enhances_vertebral_bone_formation_in_ovariectomized_minipigs_ L2 - https://doi.org/10.1007/s00198-015-3230-y DB - PRIME DP - Unbound Medicine ER -