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. 1998 Oct;57(10):614–618. doi: 10.1136/ard.57.10.614

Bisphosphonates in bone cement inhibit PMMA particle induced bone resorption

A Sabokbar 1, Y Fujikawa 1, D Murray 1, N Athanasou 1
PMCID: PMC1752488  PMID: 9893573

Abstract

OBJECTIVE—Wear particle induced bone resorption is thought to be one of the mechanisms that contribute to implant loosening. It has previously been shown that macrophages, in response to polymethylmethacrylate (PMMA) particles, differentiate into bone resorbing osteoclasts, and that this process is inhibited by a bisphosphonate, etidronate (EHDP). The aim of this study was to determine whether incorporating EHDP in bone cement could reduce PMMA associated bone resorption.
METHODS—Two concentrations of EHDP were mixed with PMMA monomer before polymerisation. Particles of PMMA (1-10 µm) were generated then added to mouse monocytes cocultured with UMR106 rat osteoblast-like cells and the extent of osteoclast differentiation was determined by assessing the extent of tartrate resistant acid phosphatase (TRAP) staining and measuring the amount of lacunar bone resorption.
RESULTS—The addition of PMMA to monocyte-UMR106 cocultures resulted in a marked increase in the number of TRAP positive osteoclast-like cells and a significant increase in the number of lacunar resorption pits compared with control cultures to which no particles had been added. After the addition of particles of PMMA + 20 mg EHDP, significantly fewer lacunar pits (p=0.00006) and fewer TRAP positive cells were noted compared with cocultures containing PMMA particles alone.
CONCLUSIONS—These results indicate that by mixing a bisphosphonate with bone cement, it is possible to inhibit PMMA particle induced bone resorption. This bisphosphonate inhibition of PMMA biomaterial wear particle containing macrophage-osteoclast differentiation and bone resorption may provide a possible therapeutic strategy to prevent or to control the osteolysis of aseptic loosening.

 Keywords: bisphosphonate; bone resorption; aseptic loosening; macrophages

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Figure 1  .

Figure 1  

Figure 1  

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(a) Indirect immunoperoxidase staining for F4/80 antigen of 24 hour coculture of UMR106 cells and monocytes showing positive reaction (brown staining) for F4/80 antigen on isolated cells (a) in the absence (× 630), and (b) in the presence of PMMA particles that have been phagocytosed (arrow) (× 1000, oil immersion).

Figure 2  .

Figure 2  

Figure 2  

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Histochemical staining for TRAP in seven day cocultures of UMR106 cells and murine monocytes showing: (a) numerous clusters of TRAP+ cells in control cocultures containing PMMA particles (× 100); (b) reduction of TRAP+ cell cluster formation in cocultures containing PMMA particles + 20 mg EHDP (× 100).

Figure 3  .

Figure 3  

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SEM photomicrograph of human bone slice cultured for 14 days in the presence of UMR106 cells, mouse monocytes, 1,25(OH)2D3 and PMMA particles. This shows extensive lacunar bone resorption with the formation of numerous resorption pits (black bar = 100 µm).

Figure 4  .

Figure 4  

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Effect of addition of particles of PMMA + EHDP (5 and 20 mg) and PMMA alone on the mean number of lacunar pits formed on bone slices after 14 days incubation in the presence of UMR106 cells and mouse monocytes. Levels of significance, using Student's paired t test, are indicated.

Selected References

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