Trystan Casey
Electrical stimulation has been shown to promote bone healing and regeneration in animal experiments and clinical treatments. The exact mechanism by which electrical stimulation enhances bone repair is not yet fully understood, but it is believed to be related to changes in growth factors and transmembrane signalling. Electrical stimulation has been found to be effective in enhancing bone healing in spinal fusion and nonunions, and there are currently 9 FDA-approved electrical bone growth stimulators commercially available for this purpose. Electrical stimulation is also being investigated as a potential treatment for congenital pseudarthrosis and osteoporosis.
| Characteristics | Values |
|---|---|
| Types of electrical stimulation methods | Direct current (DC), capacitive coupling (CC), inductive coupling (IC) |
| Direct current (DC) | Lowers oxygen level and increases pH, causing an increase in osteoblast cell proliferation |
| Capacitive coupling (CC) | Increases intracellular calcium, enhancing activated calmodulin stores and cell proliferation |
| Inductive coupling (IC) | Enhances osteoblast differentiation and proliferation by altering growth factors, gene expression, and transmembrane signaling |
| Bone healing applications | Spinal fusion, fracture nonunion, osteoporosis, congenital pseudarthroses |
| Benefits | Enhanced bone healing and regeneration, reduced pain, lower healthcare costs compared to non-stimulation treatments |
| Limitations | Inconsistent results, cumbersome devices, varying treatment regimes, unclear mechanism of action |
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What You'll Learn
Direct current electrical stimulation
DC ES works by an electrochemical reaction at the cathode (O2 + 2H2O + 4e− → 4OH), creating end products referred to as faradic products. The production of hydroxyl ions (OH) at the cathode lowers the oxygen concentration and increases the pH. This environment prevents bone resorption and increases bone formation by increasing osteoblast and decreasing osteoclast action.
A second faradic product, hydrogen peroxide (H2O2), is also formed at the cathode, which enhances osteoclast differentiation. The resorption by the osteoclasts triggers bone formation by the osteoblasts. The effect of H2O2 could also be due to its stimulatory action on vascular endothelial growth factor secretion by macrophages, which is important for angiogenesis in fracture healing.
DC ES has been shown to promote bone healing and regeneration in animal experiments and clinical treatments. It is also effective in enhancing bone healing in spinal fusion. However, the exact mechanism by which DC ES enhances bone repair remains underexplored and requires further clinical studies.
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Inductive coupling
Electrical stimulation (EStim) has been shown to promote bone healing and regeneration in animal experiments and clinical treatments. There are three modalities of electrical stimulation: direct current electrical stimulation (DCES), capacitive coupling (CC), and inductive coupling.
In vitro studies demonstrate that electrical stimulation enhances bone healing by changes in growth factors and transmembrane signalling, although no clear mechanism has been defined. The majority of studies utilized inductive coupling with LOE-1 supporting its application for healing osteotomies and nonunions.
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Capacitive coupling
CC causes an increase in intracellular calcium through voltage-gated calcium channels. This enhances activated calmodulin stores, which in turn increases cell proliferation. This process enhances callus formation and maturation, leading to bone healing.
CC has been shown to enhance bone healing in nonunions. In vitro studies have demonstrated that CC increases cystolic calcium, which then increases intracellular calcium. This process enhances activated calmodulin stores, which increase cell proliferation and enhance callus formation and maturation, ultimately leading to bone healing.
CC has also been shown to up-regulate the mRNA expression for bone morphogenic proteins (BMPs), which may represent an alternative mechanism by which CC influences osteogenesis. In addition, CC has been found to increase growth factors, which are important for the proliferation and differentiation of osteoblastic cells.
Overall, CC is a promising non-invasive method of ES that can enhance bone healing, particularly in nonunions. However, more clinical studies are needed to optimize its use in clinical practice.
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Bone tissue engineering
The success of BTE approaches depends on the choice of cells, scaffold material, and signalling stimuli added to the cell-scaffold mix and/or present in the microenvironment of the healing defect. Electrical stimulation (EStim) has been shown to promote bone healing and regeneration in animal experiments and clinical treatments. EStim enhances bone healing by changes in growth factors and transmembrane signalling, although the exact mechanism has not yet been defined.
Direct current (DC) EStim lowers oxygen levels and increases pH, causing an increase in osteoblast cell proliferation, which enhances callus formation and maturation, leading to bone healing. Capacitive coupling (CC) increases cytosolic calcium through voltage-gated calcium channels, enhancing cell proliferation and bone healing. Inductive coupling (IC) enhances osteoblast differentiation and proliferation by altering growth factors, gene expression, and transmembrane signalling.
In vitro studies have successfully induced osteogenesis with all electrical stimulation modalities: direct current, pulsed electromagnetic field, and capacitive coupling. However, large animal studies have been largely unsuccessful with non-invasive modalities, possibly due to issues of scale and tissue plane thickness.
Wearable EStim devices can be cumbersome and interfere with patients' daily activities, leading to decreased compliance. Surgically implanted devices, on the other hand, have reported more consistent treatment outcomes as the electrical energy is focused on the fracture site.
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Clinical efficacy
The clinical efficacy of electrical stimulation in bone healing has been the subject of numerous studies, with promising results. Electrical stimulation has been shown to promote bone healing and regeneration in both animal experiments and clinical treatments. This has led to its application in bone tissue engineering treatments (BTE) as an alternative to conventional treatments for large non-healing bone defects. BTE approaches simulate bone autografts by filling the defect with bone-forming stem/progenitor cells and growth factors that control cell-cell and cell-scaffold interactions.
Several mechanisms have been proposed to explain the effectiveness of electrical stimulation in bone healing. One such mechanism involves the electrochemical reaction at the cathode during direct current (DC) stimulation, which lowers oxygen levels and increases pH. This environment prevents bone resorption and increases bone formation by affecting osteoblast and osteoclast action. Another mechanism involves capacitive coupling (CC), which increases intracellular calcium levels, enhancing cell proliferation and bone healing. Inductive coupling, predominantly in the form of pulsed electromagnetic field (PEMF) therapy, has also been shown to enhance osteoblast differentiation and proliferation through various pathways.
The success of BTE approaches and electrical stimulation depends on factors such as the choice of cells, scaffold material, and signalling stimuli. While electrical stimulation has shown promising results in pre-clinical animal studies and clinical settings, the optimal stimulation modality and specifications for humans remain to be determined. Large animal models offer more insight into clinically useful bone growth stimulators due to their similarity in scale and capacity for bone healing to humans.
While electrical stimulation has demonstrated positive outcomes, there are some considerations regarding its clinical efficacy. The wearable devices used for prolonged periods can interfere with patients' daily activities and lead to decreased compliance. Additionally, inconsistent results have been reported, attributed partly to the stimulation energy not being focused on the fracture site. The effectiveness of bone stimulators for bone fracture healing remains unclear, with researchers reporting mixed results. Further well-controlled, randomised clinical studies are needed to conclusively establish the clinical efficacy and safety of electrical stimulation methods.
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Frequently asked questions
Electrical stimulation (EStim) is an alternative therapy that has been shown to promote bone healing and regeneration in both animal experiments and clinical treatments. Devices such as bone stimulators are often used for fractures that have failed to heal on their own.
Electrical stimulation works by influencing the arrangement, migration, proliferation, and differentiation of osteoblasts by inducing an electrochemical reaction at the cathode. This lowers oxygen concentration and increases pH, preventing bone resorption and increasing bone formation.
Electrical stimulation has been found to be effective in enhancing bone healing, particularly in spinal fusion. It has also been shown to reduce pain and lower rates of persistent nonunions.
The effectiveness of bone stimulators for bone fracture healing remains unclear, with researchers reporting mixed results. While electrical stimulation has no known adverse side effects, it may not be suitable for all types of fractures, especially acute fractures, due to the need for surgery and the risk of infection.
