Local application of alendronate controls bone formation and ß-tricalcium phosphate resorption induced by recombinant human bone morphogenetic protein-2.

This study examined the ability of local alendronate (ALN) administration to control ß-tricalcium phosphate (ß-TCP) resorption as well as the induction of bone formation by recombinant human bone morphogenetic protein-2 (rhBMP-2). A 15-mm critical-sized bone defect was created in the diaphysis of rabbit ulnae. Nine female rabbits (4 to 5 months-old) were divided into 3 groups. Group 1 (n = 6 ulnae) animals received implants consisting of ß-TCP granules and 25 µg of rhBMP-2 in 6.5% collagen gel. Group 2 (6 ulnae) and Group 3 (6 ulnae) animals received the same implants, but with 10-6 M and 10-3 M ALN-treated TCP granules, respectively. Two weeks postsurgery, tartrate-resistant acid phosphatase-positive cell counts, new bone formation, and residual ß-TCP were evaluated. This study showed that a high dose of ALN strongly reduced osteoclastic resorption of ß-TCP induced by rhBMP-2, resulting in decreased bone formation. In contrast, a low dose of ALN slightly reduced the bone resorptive effect but increased bone formation. These results suggest that osteoclast-mediated resorption plays an important role in bone formation and a coupling-like phenomenon could occur in the ß-TCP-implanted area, and that administration of a low dose of ALN may solve clinical bone resorptive problems induced by rhBMP-2.

Effects of micro-porosity and local BMP-2 administration on bioresorption of ß-TCP and new bone formation.

BACKGROUND: It has been reported that the microporous structure of calcium phosphate (CaP) ceramics is important to osteoconduction. Bone morphogenetic protein-2 (BMP-2) has been shown to be a promising alternative to bone grafting and a therapeutic agent promoting bone regeneration when delivered locally. The aim of this study was to evaluate the effects of micro-porosity within beta-tricalcium phosphate (ß-TCP) cylinders and local BMP-2 administration on ß-TCP resorption and new bone formation. METHODS: Bilateral cylindrical bone defects were created in rabbit distal femora, and the defects were filled with ß-TCP. Rabbits were divided into 3 groups; defects were filled with a ß-TCP cylinder with a total of approximately 60% porosity (Group A: 13.4% micro- and 46.9% macropore, Group B: 38.5% micro- and 20.3% macropore, Group C: the same micro- and macro-porosity as in group B supplemented with BMP-2). Rabbits were sacrificed 4, 8, 12, and 24 weeks postoperatively. RESULTS: The number of TRAP-positive cells and new bone formation in group B were significantly greater than those in group A at every period. The amount of residual ß-TCP in group C was less than that in group B at all time periods, resulting in significantly more new bone formation in group C at 8 and 12 weeks. The number of TRAP-positive cells in group C was maximum at 4 weeks. CONCLUSIONS: These results suggest that the amount of submicron microporous structure and local BMP-2 administration accelerated both osteoclastic resorption of ß-TCP and new bone formation, probably through a coupling-like phenomenon between resorption and new bone formation.