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This study examined the ability of local alendronate (ALN) administration to control β-tricalcium phosphate (β-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 β-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 β-TCP were evaluated. This study showed that a high dose of ALN strongly reduced osteoclastic resorption of β-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 β-TCP-implanted area, and that administration of a low dose of ALN may solve clinical bone resorptive problems induced by rhBMP-2., (© 2019 Wiley Periodicals, Inc.)

The aim of this study was to determine the effects of alendronate (ALN) on osteoclastic resorption of beta-tricalcium phosphate (beta-TCP) and bone formation. beta-TCP blocks of 75% porosity, with or without ALN treatment, were implanted into cavities drilled in rabbit femoral condyles. New bone formation, residual amount of beta-TCP, and the number of tartrate-resistant acid phosphatase-positive cells were evaluated 2 weeks after surgery. The results show that local application of ALN at a concentration of 10(-2) to 10(-6)M reduced the number of osteoclasts on the surface of beta-TCP. New bone formation was also inhibited by ALN in a dose-dependent manner. Thus, inhibition of osteoclast formation resulted in reduced beta-TCP resorption and bone formation. These results suggest that osteoclast-mediated resorption plays an important role in bone formation and a coupling-like phenomenon could occur in beta-TCP-filled bone defects., (Copyright 2009 Wiley Periodicals, Inc.)

Background: The role of bone formation and bioresorption in an early stage after implantation of beta-tricalcium phosphate (beta-TCP) was investigated using scanning and transmission electron microscopy (SEM, TEM)., Methods: The ceramic beta-TCP cylinders were implanted into cavities drilled in the femoral condyles of eight NZW rabbits. Four of the rabbits were sacrificed at 2 weeks and four at 4 weeks after implantation, respectively. The femoral condyles were excised to prepare the specimens for SEM and TEM., Results: SEM showed giant cells of more than 20 mum in diameter were observed on the surface of beta-TCP at 2 weeks after implantation. TEM demonstrated that collagen fibrils secreted from the monocytic cells invaded beta-TCP micropores at 2 weeks. Multinucleated giant cells (MNGCs) were in contact with the surface of beta-TCP at 2 weeks. Some of them had a ruffled border (RB) at the cell-substrate interface, characteristic of osteoclasts., Conclusions: These findings suggest that cell-mediated disintegration by osteoclasts played a role in the bioresorption of beta-TCP at an early stage after implantation. In addition, the micropores of beta-TCP ceramic may provide an environment for collagen formation, leading to the deposition of apatite crystals. Therefore, the micropores facilitate bone ingrowth as well as ceramic resorption.

Most of the implanted porous beta-tricalcium phosphate (beta-TCP) can be resorbed. However, beta-TCP block with 75% porosity is inadequate for weight-bearing sites until bone incorporation occurs. Thus, the authors have recently developed beta-TCP block with 60% porosity, which is approximately sevenfold greater in terms of compressive strength than that of beta-TCP with 75% porosity. The authors investigated bone formation and resorption of beta-TCP after implantation in patients of beta-TCP blocks with two different porosities. From May 2003 to November 2004, medial opening high tibial osteotomy was performed in 25 patients with a mean age of 66 years. The opened defect was fixed with a Puddu plate. Then 6-8 cm(3) of beta-TCP block with 75% porosity was used to fill the cancellous bone defect, except on the medial side where 2.83-3.18 cm(3) of wedge-shaped beta-TCP block with 60% porosity was implanted. At least 2 years after surgery, the 25 patients had no correction loss, and bone formation was noted in all cases. Complete or nearly complete resorption of beta-TCP with 60 and 75% porosity was obtained within 3.5 years. Thirteen biopsy samples obtained from the 60% porosity implantation sites showed good lamellar bone formation, and the percentage of beta-TCP remaining relative to the newly formed bone plus beta-TCP ranged from 0.3 to 14.5%, with a mean of 6.7%. The authors suspect that mechanical stress loading to the medial side of the tibia facilitated bone formation and resorption of beta-TCP with 60% porosity., ((c) 2007 Wiley Periodicals, Inc.)

The objective of this study was to evaluate the effects of a complex of beta-tricalcium phosphate (beta-TCP) granules and 3.5% hyaluronate (beta-TCP granules-HY complex) compared with a beta-TCP block, in terms of osteoconductivity and biodegradability, to determine whether this complex would be a good candidate for bone void filler. Both materials were implanted into cavities drilled in rabbit femoral condyles. New bone formation and mineral apposition rate were evaluated to analyze osteoconductivity, whereas residual beta-TCP within the defects and tartrate-resistant acid phosphatase (TRAP) cellular activity were studied for beta-TCP resorption. The results show that both the beta-TCP block and the beta-TCP granules-HY complex support bone ingrowth; however, bioresorption was rapid for beta-TCP granules-HY but weak for beta-TCP block. This biodegradation mechanism was considered to be a cell-mediated disintegration by numerous TRAP-positive giant cells. The time lag between the peak value of TRAP-positive giant cell population and that of new bone formation rate suggests that a coupling-like phenomenon could be occurring in the beta-TCP-filled bone defects. In addition, beta-TCP granules-HY complex, which is an injectable, pastelike material, has similar osteoconductive properties to beta-TCP block. Thus, this complex may be useful as a bone filler in clinical application.

Most of the implanted porous β‐tricalcium phosphate (β‐TCP) can be resorbed. However, β‐TCP block with 75% porosity is inadequate for weight‐bearing sites until bone incorporation occurs. Thus, the authors have recently developed β‐TCP block with 60% porosity, which is approximately sevenfold greater in terms of compressive strength than that of β‐TCP with 75% porosity. The authors investigated bone formation and resorption of β‐TCP after implantation in patients of β‐TCP blocks with two different porosities. From May 2003 to November 2004, medial opening high tibial osteotomy was performed in 25 patients with a mean age of 66 years. The opened defect was fixed with a Puddu plate. Then 6–8 cm3 of β‐TCP block with 75% porosity was used to fill the cancellous bone defect, except on the medial side where 2.83–3.18 cm3 of wedge‐shaped β‐TCP block with 60% porosity was implanted. At least 2 years after surgery, the 25 patients had no correction loss, and bone formation was noted in all cases. Complete or nearly complete resorption of β‐TCP with 60 and 75% porosity was obtained within 3.5 years. Thirteen biopsy samples obtained from the 60% porosity implantation sites showed good lamellar bone formation, and the percentage of β‐TCP remaining relative to the newly formed bone plus β‐TCP ranged from 0.3 to 14.5%, with a mean of 6.7%. The authors suspect that mechanical stress loading to the medial side of the tibia facilitated bone formation and resorption of β‐TCP with 60% porosity. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [ABSTRACT FROM AUTHOR]