The GDF5 mutant BB-1 may be superior to GDF5 for the enhancement of bone formation induced by an injectable, PLGA-fiber reinforced, brushite-forming cement in a sheep defect model of lumbar osteopeniaThursday (09.05.2019) 12:10 - 12:30 Part of:
Objectives: Targeted delivery of osteoinductive bone morphogenetic proteins (BMPs) in bioresorbable calcium phosphate cement (CPC), potentially suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures, may be required to counteract augmented local bone catabolism and support complete bone regeneration. The BMPs GDF5 (BMP-14) and its biologically optimized mutant BB-1 (GDF-5V453/V456 protein) represent attractive drug candidates for this purpose [1,2]. The present study compares the effects of an injectable, poly (l-lactide-co-glycolide) acid (PLGA)-fiber reinforced, brushite-forming cement (CPC) containing low-dose BB-1 or GDF5 in a sheep lumbar osteopenia model.
Methods: Bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep, treated with poly(l-lactide-co-glycolide acid)-fiber-reinforced, brushite-forming CPC without (L4) or with BMP (L5; 5, 100, and 500 g GDF5/BB-1; n=5-6 for GDF5; n=6 for BB-1 each), and compared with an untouched control (L1). Three and 9 months post-operation, effects of CPC±GDF5/BB-1 were documented by osteodensitometry, static histomorphometry and biomechanical testing.
Results: Compared to untouched controls, CPC±GDF5/BB-1 numerically or significantly improved all parameters at 3 and 9 months. Significantly stronger effects of BB-1 compared to GDF5 were observed at 3 months for bone volume/total volume (BV/TV; p≤0.05; 5 μg), trabecular number (Tb.N; p≤0.05; 500 μg) and osteoid thickness (O.Th; p≤0.05; 500 μg). BB-1 significantly enhanced the bone formation induced by CPC+fibers also at 9 months, as demonstrated for bone mineral density (BMD; p≤0.05 vs. GDF5; 500 μg), osteoid volume/bone volume (OV/BV; p≤0.05 vs. GDF5; 100 μg) and osteoid thickness (O.Th; p≤0.05 vs. GDF5; 100 μg). There were no signs of inflammatory infiltration close to or distant from the injection channel in L4 or L5 in the treatment with either GDF5 or BB-1 at any time point.
Conclusions: The novel GDF5 mutant BB-1 may be more effective than GDF5 and could thus be used in CPC for the vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.
 Bungartz M. et al. Spine J. 2017 Nov;17(11):1685-1698. doi: 10.1016/j.spinee.2017.06.007. Epub 2017 Jun 19.
 Gunnella F et al. Spine J. 2018 Feb;18(2):357-369. doi: 10.1016/j.spinee.2017.10.002. Epub 2017 Oct 12.