Low-dose BMP-2 enhances the bone-forming effects of an injectable, PLGA fiber-reinforced, brushite-forming cement in sheep lumbar osteopenia defectsPart of:
Objectives: Injectable calcium phosphate cements (CPC) represent resorbable, bioactive, osteoconductive alternatives to bioinert polymethylmethacrylate cement in the treatment of osteoporotic vertebral fractures. To improve their regenerative potential, CPC can be loaded with bone specific growth factors, e.g. bone morphogenic proteins (BMPs) such as BMP-2. The present 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.
Methods: Bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep, treated with PLGA-fiber-reinforced CPC without (L4) or with BMP-2 (L5; 1, 5, 100, and 500 μg BMP-2; n=5-6 each), and compared with an untouched control (L1). Three and 9 months post-operation, effects of CPC±BMP-2 were documented by osteodensitometry, histomorphometry, micro-CT, and biomechanical testing.
Results: Compared to untouched controls, CPC±BMP-2 numerically or significantly improved all bone formation, bone resorption, and bone structure parameters. 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.
Conclusions: BMP-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.