The finding that alterations in electrical potential play an important role in the mechanical stimulation of the bone provoked hype that noninvasive extremely low frequency pulsed electromagnetic fields (ELF-PEMF) can be used to support healing of bone and osteochondral defects. This resulted in the development of many ELF-PEMF devices for clinical use. Due to the resulting diversity of the ELF-PEMF characteristics regarding treatment regimen, and reported results, exposure to ELF-PEMFs is generally not among the guidelines to treat bone and osteochondral defects. Notwithstanding, here we show that there is strong evidence for ELF-PEMF treatment. We give a short, confined overview of in vitro studies investigating effects of ELF-PEMF treatment on bone cells, highlighting likely mechanisms. Subsequently, we summarize prospective and blinded studies, investigating the effect of ELF-PEMF treatment on acute bone fractures and bone fracture non-unions, osteotomies, spinal fusion, osteoporosis, and osteoarthritis. Although these studies favor the use of ELF-PEMF treatment, they likewise demonstrate the need for more defined and better controlled/monitored treatment modalities. However, to establish indication-oriented treatment regimen, profound knowledge of the underlying mechanisms in the sense of cellular pathways/events triggered is required, highlighting the need for more systematic studies to unravel optimal treatment conditions.
It is well accepted that bone is a mechanosensory organ, which requires continuous strain to preserve its functional structure and prevent disuse bone loss (osteopenia or osteoporosis). The resulting premise that bones constantly adapt to meet their mechanical demands is referred to as Wolff’s law [1
]. In the 1960s, it was first reported that mechanical strain alters the electrical potential along the lateral and longitudinal axes of compact bone, providing local stimuli for bone-forming cells [2
]. Bassett and colleagues suggest collagen piezoelectricity as a potential underlying mechanism. According to their theory, applied stress generates local potential gradients along the collagen fibers [3
]. This mechanism, ascribed to the non-centrosymmetric nature of collagen, is well accepted for dry bone tissue [5
]. However, for wet bone tissue, there was more and more experimental evidence that fluid-induced shear stress and associated streaming potentials cause the strain-generated potentials [6
]. Offering a possible explanation of how bone is selectively deposited at mechanically challenged areas, these described phenomena raised hope in the scientific community that these mechanisms can be utilized to support bone function and fracture healing. Anecdotal reports that electromagnetic fields fostered healing of persistent non-union fractures further fueled the interest in this area [7
]. In these studies, mainly extremely low frequency pulsed electromagnetic fields (ELF-PEMFs) have been applied.
2. In Vitro Evidence for ELF-PEMF Effects on Bone Cells
Within the bioelectromagnetic science society, certain theories on how natural and artificial ELF-PEMF may induce cellular effects on the molecular level are discussed, for example, the molecular gyroscope model [12
], Lorentz models [13
], DNA antenna model [15
], radical pair model [16
], and ion cyclotron resonance [17
]. Cells in the human body are continuously exposed to electrical charges (e.g., Na2+
, or Cl−
ion gradients, which regulate cellular membrane potentials) involved in a manifold of cellular processes [18
]. Therefore, it is also feasible that ELF-PEMFs influence cellular responses by influencing these natural ion gradients, either passively by ionic forces or actively by regulating so-called voltage-gated ion channels [19
]. However, it might well be that the effects triggered by ELF-PEMFs can be only explained by a combination of these theories. Focusing on the bone, studies have demonstrated that ELF-PEMF treatment is reported to cause calcium flux, induce RNA expression, stimulate synthesis of extracellular matrix proteins and growth factors, and initiate signaling cascades involved in viability, proliferation, and differentiation. Some of these ELF-PEMF effects on viability, growth, and function of bone cells will be described in more detail in the following paragraphs.