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 A2A and A3 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.
The musculoskeletal system is highly responsive to its physicochemical environment. Bone and cartilage cells respond to changes in mechanical stress, fluid flow, pH, and pO2 by altering their phenotype and expressing a range of signaling and structural molecules that result, in particular, in an altered extracellular matrix (ECM) organization and associated biomechanical properties. Response to mechanical stress is perhaps the best recognized and intuitively obvious of skeletal environmental conditions, facilitating adaptation and modeling to changing biomechanical and environmental requirements perhaps through intermediary strain-associated signaling events. In addition to mechanical stress, skeletal tissues, both bone and cartilage, demonstrate an exquisite sensitivity to electrical and electromagnetic stimulation.
Responses of skeletal cells to pulsed electromagnetic field (PEMF) have been exploited therapeutically with devices that expose tissues to appropriately configured fields to stimulate ECM synthesis for bone and cartilage repair. This review highlights key processes in cell responses to PEMF as follows: (1) signal transduction through cell membrane adenosine receptors (ARs), (2) the activation of osteoinductive pathways, and (3) the synthesis of skeletal ECM including structural and signaling molecules. These actions are reflected physiologically in bone as the healing of fractures, osteotomies, and nonunions, and, in joints, as the modulation of cartilage damage and reduction in catabolic and inflammatory cytokines in arthritis. Understanding the cellular responses to PEMF will inform clinical studies, may point to key issues that need further investigation, and will be relevant in promoting bone and cartilage repair, tissue engineering and regeneration in a repair mode, and damping inflammation in arthritis. Understanding the pathways of the activity of PEMFs provides a solid mechanistic basis for their clinical use.
Studies:
-
Bassett, C. A., Mitchell, S. N., & Schink-Ascani, M. (1982) This study investigated the effects of PEMF on delayed unions and non-unions in long bone fractures. The authors found that treatment with PEMF resulted in a high success rate of healing, with 81.8% of the non-unions treated uniting successfully.
-
Sharrard, W. J. (1990) This randomized, double-blind, placebo-controlled trial examined the effects of PEMF on the healing of tibial fractures. The study found that patients treated with PEMF experienced faster fracture healing compared to the control group.
-
Hannemann, P. F., Mommers, E. H., Schots, J. P., Brink, P. R., & Poeze, M. (2014) This systematic review and meta-analysis evaluated the effectiveness of PEMF in the treatment of acute fractures. The authors concluded that PEMF therapy led to a significantly higher rate of healing compared to the control group, indicating its potential in enhancing fracture repair.
-
Aaron, R. K., Wang, S., & Ciombor, D. M. (2002) This review article discussed the effects of PEMF on osteogenesis and bone healing. The authors highlighted the various cellular and molecular mechanisms by which PEMF promotes bone formation and repair, including increased blood flow, enhanced cellular activity, and the regulation of gene expression.
-
Tabrah, F., Hoffmeier, M., Gilbert, F., Batkin, S., & Bassett, C. A. (1990) This study investigated the effects of PEMF on bone density in a group of patients with osteoporosis. The authors found that patients treated with PEMF experienced significant improvements in bone density compared to the control group, suggesting that PEMF therapy could be beneficial for individuals with osteoporosis.