Pulsed Electromagnetic Field Stimulation of Bone Healing and Joint Preservation: Cellular Mechanisms of Skeletal Response

Abstract

The US FDA has approved pulsed electromagnetic fields (PEMFs) as a safe and effective treatment for nonunions of bone. Despite its clinical use, the mechanisms of action of electromagnetic stimulation of the skeleton have been elusive. Recently, cell membrane receptors have been identified as the site of action of PEMF and provide a mechanistic rationale for clinical use. This review highlights key processes in cell responses to PEMF as follows: (1) signal transduction through A 2A and A 3 adenosine cell membrane receptors and (2) dose-response effects on the synthesis of structural and signaling extracellular matrix (ECM) components. Through these actions, PEMF can increase the structural integrity of bone and cartilage ECM, enhancing repair, and alter the homeostatic balance of signaling cytokines, producing anti-inflammatory effects. PEMFs exert a proanabolic effect on the bone and cartilage matrix and a chondroprotective effect counteracting the catabolic effects of inflammation in the joint environment. Understanding of PEMF membrane targets, and of the specific intracellular pathways involved, culminating in the synthesis of ECM proteins and reduction in inflammatory cytokines, should enhance confidence in the clinical use of PEMF and the identification of clinical conditions likely to be affected by PEMF exposure.

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

“…PEMFs are an FDA-approved treatment for fracture nonunions [ 49 ]. In literature the efficacy of PEMFs in treating tibial delayed unions or nonunions has been reported from 45% to 87% [ 50 ].…”

Pulsed Electromagnetic Field Alleviates Intervertebral Disc Degeneration by Activating Sirt1-Autophagy Signaling Network

“…It is well known that PEMF exerts its therapeutic effect via regulation of metabolic pathways ( Cadossi et al, 2020 ). This occurs via regulation of cell proliferation, differentiation, and maturation, particularly in the treatment of musculoskeletal diseases ( Yang et al, 2021 ; Liu et al, 2022 ).…”

Biophysical Modulation of Mesenchymal Stem Cell Differentiation in the Context of Skeletal Repair

“…A recent review has focused on the role of signal transduction in PEMF efficacy and has described controlled studies of PEMF-stimulated bone repair. Anabolic effects of PEMF on articular cartilage are described as well [ 68 ]. The biologic responses of engrafted MSCs to PEMF have not been described but hold substantial theoretical promise.…”

“…PEMF has been used extensively in the clinical enhancement of skeletal repair and its tissue-based mechanisms have recently been reviewed [ 68 ]. The cytokine-mediated relationship between angiogenesis and fracture repair has been well described [ 70 ].…”