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Polymethylmethacrylate-induced inflammatory macrophages resorb bone
J Quinn1, C Joyner, J T Triffitt
1Nuffield Department of Pathology and Bacteriology, John Radcliffe Hospital, Headington, Oxford, England.
Abstract:
Macrophages and their fused products are commonly found at the polymethylmethacrylate cement-bone interface, but it is not known if they contribute directly to the osteolysis associated with loosening of the cemented prosthesis. We isolated mononuclear phagocytes from granulomas formed by subcutaneous implantation of polymethylmethacrylate into mice and incubated them on bone slices in which they formed resorption lacunae after co-culture for seven to 14 days with both marrow stromal cells and osteoblast-like cells (in the presence of 1 alpha,25-dihydroxyvitamin D3 and dexamethasone). Increased numbers of tartrate-resistant acid phosphatase-positive mononuclear and multinucleated cells formed in these cultures. Both in the presence and absence of stromal cells, macrophages produced extensive superficial roughening of the bone surface. Polymethylmethacrylate-induced macrophages are thus capable of low-grade surface and high-grade lacunar osteolysis, the latter requiring the presence of specific hormonal and stromal cell elements. These two forms of bone resorption could account for the pathogenesis and clinical patterns associated with loosening of the cemented prosthesis.
Insights
Macrophages near polymethylmethacrylate cement can cause bone loss, potentially explaining why cemented prostheses loosen. This osteolysis requires specific cellular and hormonal factors for significant bone resorption.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Orthopedic Surgery
Background:
- Macrophages accumulate at the polymethylmethacrylate (PMMA) cement-bone interface in cemented prostheses.
- The direct role of these macrophages in PMMA-associated osteolysis and prosthesis loosening remains unclear.
Purpose of the Study:
- To investigate the osteolytic potential of macrophages derived from PMMA-induced granulomas.
- To determine the conditions under which these macrophages mediate bone resorption.
Main Methods:
- Isolation of mononuclear phagocytes from PMMA-induced mouse granulomas.
- Co-culture of macrophages with bone slices, marrow stromal cells, and osteoblast-like cells under specific hormonal conditions (1α,25-dihydroxyvitamin D3 and dexamethasone).
- Assessment of bone resorption through lacunae formation and surface changes, and identification of tartrate-resistant acid phosphatase-positive cells.
Main Results:
- PMMA-induced macrophages formed resorption lacunae on bone slices.
- Increased tartrate-resistant acid phosphatase-positive mononuclear and multinucleated cells were observed.
- Macrophages induced superficial bone roughening, with significant lacunar osteolysis occurring in the presence of hormonal and stromal support.
Conclusions:
- PMMA-induced macrophages possess the capacity for both superficial and lacunar osteolysis.
- Lacunar osteolysis by these macrophages is dependent on specific hormonal and stromal cell interactions.
- These findings suggest a mechanism for PMMA-associated osteolysis contributing to cemented prosthesis loosening.