Electrical and Mechanical Bone Growth Stimulation



Electrical and Mechanical Bone Growth Stimulation


Michael S. Downey

Wen-Yin Choi Wang



Electrical energy was first described in an effort to achieve bone healing in 1812 when Birch was credited with the healing of a tibial nonunion by “shocks of electric fluid” passed between the fractured ends of the bone (1). Subsequently, sporadic reports of the use of electricity in bone healing were described over the next 150 years. In 1957, the investigation into bone healing with electricity was reinvigorated by the work of Fukada and Yasuda (2), who demonstrated that the mechanical deformation of bone produced electrical potentials. In 1971, Friedenberg et al (3) used direct current (DC) for the management of a nonunion of the medial malleolus. In 1981, Brighton et al (4) reported their results in a multicenter evaluation on the use of constant DC for the management of osseous nonunion. The initial description of a totally implantable DC bone stimulator appears to have been that of Dwyer and Wickham in 1974 (5). In 1981, the first application of a noninvasive method of bone growth stimulation was described by Bassett et al (6), when they applied pulsed electromagnetic fields (PEMFs) in the treatment of a tibial diaphyseal nonunion.

A variety of therapeutic devices are available to provide electrical and mechanical stimulation for the augmentation of bone healing. In addition, the same devices have been studied and/or applied in the management of other clinical problems, including the treatment of avascular necrosis, congenital pseudarthrosis, failed and initial arthrodesis, osteoporosis, chronic refractory tendonitis, osteoarthritis, stress fractures, and acute Charcot osteoarthropathy. Electrical stimulation of nonunited fractures and osteotomies, particularly when applied in a noninvasive manner, is generally reported as being safe. A diagnostic and therapeutic technology assessment by the American Medical Association concluded, “the safety of noninvasive electrical stimulation for the treatment of nonunions has been established” (7).

Numerous retrospective and prospective studies appear to attest to the effectiveness of electrical and ultrasonic stimulation in the management of nonunions and fresh fractures (8,9,10,11,12 and 13). More recently, several systematic review and meta-analyses of randomized trials have further supported the value of electrical and mechanical stimulation in bone healing (14,15,16 and 17). Although these studies collectively support the use of electrical and mechanical stimulation in the healing of nonunions and fresh fractures, further study with large scale, randomized trials is needed to make broad and decisive conclusions regarding these modalities.


BIOPHYSICS OF BONE HEALING

It is well known that changes in the environment or forces applied to bone and joints result in adaptation within these structures. Adaptation of bone in response to environmental factors is explained by Wolff’s law, which states “The law of bone remodeling is that mathematical law according to which observed alterations in the internal architecture and external form of bone occur as a consequence of the change in shape and/or stressing of bone” (18).

The alterations in the radiographic appearance of bone in response to stress and the sequential changes of healing or remodeling of bone following fracture or osteotomy imply that from an engineering viewpoint, bone must possess a control system that is activated during various stages of physiologic function (19). In recent years, researchers studying the structural adaptations of bone to stress and other applied forces have focused on the electromechanical properties of osseous tissue as a means by which these alterations are mediated.

In 1957, Fukada and Yasuda (2) demonstrated that when stress is applied to a bone in such a manner as to cause deformity, electrical potentials are generated within the bone. The appearance of electrical potentials within bone in response to the application of an external force is referred to as a piezoelectric property. The electrical signals generated within bone in response to stress are known as endogenous stress-related potentials (20).


ENDOGENOUS STRESS-RELATED POTENTIALS

Two sources of endogenous stress-related potentials appear to exist within bone—piezoelectric and electrokinetic. The potentials are biphasic, producing current flow in one direction with the application of stress and in the opposite direction when that stress is removed. These potentials are of a negative polarity in areas of compression and a positive polarity in areas of tension. Bone production occurs within the electronegative areas, whereas bone resorption occurs within the electropositive areas (21) (Fig. 89.1).


STEADY-STATE POTENTIALS

In addition to stress-related potentials, bioelectric or steadystate potentials are also recorded from the surface of a living bone even when no stress has been applied and appears to be unaffected by denervation or arterial ligation.

Steady-state potentials are significantly electronegative at the site of growing bone, as exemplified by physeal plates. In addition, strongly electronegative bioelectric potentials may be recorded throughout a fractured or osteotomized bone, with the peak of electronegativity recorded at the site of bone healing (22,23).







Figure 89.1 Stress-induced piezoelectric potentials. When stress is applied to a bone, a relatively electronegative area (cathodic) is created on the side of bone compression. A relatively electropositive area (anodic) is created on the side of bone undergoing distraction (tension). Bone accretion develops in areas of compression and is driven by the relative electronegativity that is present. Bone resorption occurs in anodic areas on the tension side of the bone.


CELLULAR AND BIOCHEMICAL RESPONSE TO ELECTRICAL AND SONIC STIMULATION

Although stress-related and steady-state electrical potentials are very small, the discovery of these processes resulted in the conclusion that Wolff’s law was in effect mediated by electrical impulses. Clinically, the hypothesis that the exogenous application of electronegative currents may stimulate osteogenesis is the basis upon which bone growth stimulation is employed.

The effects of electric and electromagnetic fields on osteogenesis at the site of delayed unions and nonunions have been reported. A variety of methods to develop an exogenous electrical potential have been used, including constant DC (24,25), pulsed DC (26,27), PEMF stimulation also known as inductive coupling (28), capacitively coupled electrical fields (29,30), and combined magnetic fields (CMFs) (31). Although all of these devices administer exogenous electrical stimulation by different techniques, all have been associated with the healing of nonunions at a rate comparable with that of bone grafting (32,33).

A variety of mechanisms by which endogenous and exogenous electrical potentials stimulate bone healing have been proposed. The biochemical effects of PEMFs, reviewed by Cheng (34), include significantly increased DNA synthesis by chondroblasts, increased collagen synthesis, an increased rate of amino acid transport functions across cellular membranes, enhanced H-noradrenaline release from nerve cell lines, and reduced cellular cAMP in mouse osteoblast cultures. An increase in mRNA expression of multiple bone morphogenic proteins (BMPs), namely, BMP-2 and BMP-4, is key in mediating osteoblastic proliferation (35). These responses to PEMFs indicate accelerated metabolic activity, implying the potential for rapid healing of connective tissue. In addition, increased proteoglycan synthesis (36) in bone matrix, increased calcification of bone matrix, and increased proliferation of both osseous and cartilaginous cells have been noted in response to electrical stimulation (22).

In vitro studies aimed at the elucidation of biochemical pathways showed that initial transduction of capacitive coupling signals is at the level of the bone cell membrane, allowing for influx of calcium from the entire (essentially infinite) extracellular matrix, while inductive coupling and combined electromagnetic fields acted within or upon intracellular calcium stores. In all three instances, the final pathway is the same, leading to an increase in cytosolic calcium, and an increase in activated calmodulin, which leads to cell proliferation (37).

Ultrasound is cyclic acoustic pressure waves generated at frequencies above the human limit of hearing (roughly 20 kHz). It is a form of mechanical energy that can result in biochemical events at the cellular level and may promote bone formation in a manner comparable with the bone responses to mechanical stress postulated by Wolff’s law (12). In 1983, Duarte (38) was the first to report acceleration in the healing of fresh fractures with a low-intensity ultrasound device in animal studies. Numerous studies in other animal models and human clinical studies have confirmed the effectiveness of low-intensity ultrasound in the management of fresh fractures. One proposed mechanism is that ultrasound increases the number of degranulated mast cells at the site of injury. These degranulated mast cells cause an amplified cascade of chemical mediators, including histamine, leading to the quicker influx of inflammatory cells that initiate the bone reparative process. Vascular endothelial growth factor (VEGF) is also released, causing increased angiogenesis. Chondrogenesis and osteogenesis proceed via an increased uptake of calcium, increase in growth factors, and BMPs (39). Several studies have shown that this mechanical force modulates bone formation both in vitro and in vivo (12). The differential absorption of ultrasound may create a gradient of mechanical stain in healing bone callus that stimulates periosteal bone formation (40).

At least 30 known or probable factors have been described to explain the cellular and mechanical responses of bone to electrical stimulation and ultrasound (41). Several fundamental questions regarding the characteristics of exogenously administered electrical or electromagnetic energy and the concept of targeted biologic response remain to be investigated. In normal bone growth or repair, endogenous electrical potentials serve to autoregulate osseous metabolic processes, with changes in the physical and electrochemical environment reflected by changes in potential within the bone. This is analogous to a rheostat light switch, which may be adjusted to various levels between on and off. Whether a similar variability in an exogenously administered electrical field is necessary remains unclear. It is possible, for example, that the electrical characteristics of a recent nonunion, chronic nonunion, infected nonunion, nonunion with internal fixation, and their varying qualitative and quantitative circumstances demand greater selectivity in the characteristics of the applied fields and their interactions with endogenous bone potentials.

Finally, while many human clinical trials have tested and shown the effectiveness of bone growth stimulation, there is still significant research being done to determine the specific mechanisms of action and ideal delivery systems. Many of these studies are being performed in vitro or in animal models, and as
invaluable as these studies may be, it is important to recognize that in vivo conditions include many other factors, including intracellular and extracellular interactions.


Jul 26, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Electrical and Mechanical Bone Growth Stimulation

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