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Bisphosphonates in bone cement inhibit PMMA particle induced bone resorption
A Sabokbar1, Y Fujikawa, D W Murray
1Nuffield Orthopaedic Centre, University of Oxford.
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 microns) 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.
Insights
Incorporating etidronate (EHDP) into polymethylmethacrylate (PMMA) bone cement significantly reduced bone resorption caused by PMMA particles. This bisphosphonate effectively inhibited osteoclast differentiation and activity, offering a potential strategy against implant loosening.
Area of Science:
- Biomaterials Science
- Orthopedic Research
- Cell Biology
Background:
- Wear particle-induced bone resorption is a key factor in aseptic implant loosening.
- Polymethylmethacrylate (PMMA) particles trigger macrophage differentiation into bone-resorbing osteoclasts.
- Bisphosphonates, such as etidronate (EHDP), are known inhibitors of osteoclast activity.
Purpose of the Study:
- To investigate the efficacy of incorporating EHDP into bone cement to mitigate PMMA particle-induced bone resorption.
- To evaluate the potential of EHDP-modified bone cement as a therapeutic strategy for preventing osteolysis.
Main Methods:
- PMMA monomer was polymerized with two concentrations of EHDP.
- PMMA particles (1-10 microns) were generated and added to cocultures of mouse monocytes and UMR106 rat osteoblast-like cells.
- Osteoclast differentiation was assessed via tartrate-resistant acid phosphatase (TRAP) staining, and bone resorption was quantified by measuring lacunar pits.
Main Results:
- PMMA particles significantly increased TRAP-positive osteoclast-like cells and lacunar resorption pits compared to controls.
- The addition of PMMA with 20 mg EHDP resulted in significantly fewer resorption pits (p = 0.00006) and TRAP-positive cells.
- EHDP demonstrated a clear inhibitory effect on PMMA particle-induced osteoclastogenesis and bone resorption.
Conclusions:
- Mixing bisphosphonates like EHDP with bone cement effectively inhibits PMMA particle-induced bone resorption.
- This approach offers a promising therapeutic strategy to prevent or manage osteolysis associated with aseptic implant loosening.
- EHDP-modified bone cement could improve the longevity and success of orthopedic implants.
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