Pulsed Electromagnetic Fields in Bone Healing: Molecular Pathways and Clinical Applications

Abstract

In this article, we provide an extensive review of the recent literature of the signaling pathways modulated by Pulsed Electromagnetic Fields (PEMFs) and PEMFs clinical application. A review of the literature was performed on two medical electronic databases (PubMed and Embase) from 3 to 5 March 2021. Three authors performed the evaluation of the studies and the data extraction. All studies for this review were selected following these inclusion criteria: studies written in English, studies available in full text and studies published in peer-reviewed journal. Molecular biology, identifying cell membrane receptors and pathways involved in bone healing, and studying PEMFs target of action are giving a solid basis for clinical applications of PEMFs. However, further biology studies and clinical trials with clear and standardized parameters (intensity, frequency, dose, duration, type of coil) are required to clarify the precise dose-response relationship and to understand the real applications in clinical practice of PEMFs.

Keywords: biophysical stimulation; bone regeneration; fracture healing; fracture repair; osteogenic differentiation; pulsed electromagnetic fields (PEMFs).

Figure 1

Schematic representation of molecular pathways activated by pulsed electromagnetic fields (PEMFs). Abbreviations: A2A (adenosine receptor); alp (alkaline phosphatase gene); BMPs (bone morphogenetic proteins); ibsp (bone sialoprotein gene); col1 (collagen type 1 gene); ERK ( extracellular signal-regulated kinase 1/2); GH (growth hormone); GHR (growth hormone receptor); IGF (insulin-like growth factor); JAK-STAT (Janus kinase- signal transucer activating the transcription); MAPK (mitogen-activated protein kinase); mTOR (mammalian-mechanistic target of rapamycin); NICD (Notch intracellular domain); ocn (osteocalcin gene); opn (ostepontin gene); PTH (parathyroid hormone); runx-2 (runt-related-transcription factor 2 gene); SMAD proteins (small mothers against decapentaplegic); TGF-β (transforming growth factor-β); TGF-β RI/RII (TGF-β receptor I/receptor II); VEGF (vascular endothelial growth factor); VEGFR-2 (vascular endothelial growth factor receptor 2).