Low-dose BMP-2 is sufficient to enhance the bone formation induced by an injectable, PLGA-fiber reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia

Publication date: Available online 12 June 2017
Source:The Spine Journal
Author(s): Francesca Gunnella, Elke Kunisch, Matthias Bungartz, Stefan Maenz, Victoria Horbert, Long Xin, Joerg Mika, Juliane Borowski, Sabine Bischoff, Harald Schubert, Peter Hortschansky, Andre Sachse, Bernhard Illerhaus, Jens Günster, Jörg Bossert, Klaus D. Jandt, Frank Plöger, Raimund W. Kinne, Olaf Brinkmann
Background contextBioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted delivery of osteoinductive bone morphogenetic proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration.PurposeThe study aimed at testing an injectable, poly (l-lactide-co-glycolide) acid (PLGA)-fiber reinforced, brushite-forming cement (CPC) containing low-dose bone morphogenetic protein BMP-2 in a sheep lumbar osteopenia model.Study Design/ SettingThis is a prospective experimental animal study.MethodsBone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BMP-2 (L5; CPC+fibers+BMP-2; 1, 5, 100, and 500 µg BMP-2; n = 5 or 6 each). The results were compared to those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (± BMP-2) were analyzed ex vivo by measuring: i) bone mineral density (BMD); ii) bone structure, i.e., bone volume/total volume (assessed by micro-CT and histomorphometry), trabecular thickness, and trabecular number; iii) bone formation, i.e., osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; iv) bone resorption, i.e., eroded surface/bone surface; and v) compressive strength.ResultsCompared to untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BMP-2 (L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared to CPC without BMP-2, additional significant effects of BMP-2 were demonstrated for bone structure (bone volume/total volume, trabecular thickness, trabecular number) and formation (osteoid surface/bone surface and mineralizing surface/bone surface), as well as for the compressive strength. The BMP-2 effects on bone formation at 3 and/or 9 months were dose-dependent, with 5 to 100 µg as the optimal dosage.ConclusionsBMP-2 significantly enhanced the bone formation induced by a PLGA-fiber reinforced CPC in sheep lumbar osteopenia. A single local dose as low as ≤ 100 µg BMP-2 was sufficient to augment middle to long-term bone formation. The novel CPC+BMP-2 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty/kyphoplasty.



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