Pulsed magnetic field in the treatment of fractures in the elderly: Unraveling mechanisms and optimizing clinical practice

 Corresponding author: Palmerindo Antônio Tavares de Mendonça Néto Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Pulsed magnetic field in the treatment of fractures in the elderly: Unraveling mechanisms and optimizing clinical practice Palmerindo Antônio Tavares de Mendonça Néto 1, *, Mayara Magda Dantas Tavares de Mendonça 1, Carlos Eduardo Miranda 1, Dirceu Moraes Junior 2, Carlos Stéfano Hoffmann Brito 3, Daniel Ramos Gonçalves Lopes 4, André Câncio de Oliveira Amorim 5 and Paulo Cezar Schutz 6 1 Regenera Dor Institute; Juazeiro do Norte, Ce, Brazil. 2 Clinical Lumius, Joinville; Sc, Brazil. 3 Carlos Stéfano Institute; Belo Horizonte, Mg, Brazil. 4 Gaio and Lopes Specialty Medicine; Rio de Janeiro, Rj, Brazil. 5 Orthopedic Clinical Herculano Silva; Juazeiro do Norte, Ce, Brazil. 6 Osteoarthritis Clinic, Santa Cruz do Sul; Rio Grande do Sul, Brazil. World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 Publication history: Received on 22 September 2025; revised on 27 October 2025; accepted on 30 October 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.28.2.3689 Abstract This scientific paper explores the use of Pulsed Magnetic Field (PEMF) as a therapeutic modality in the treatment of fractures, with a special focus on its application in elderly patients. It addresses the growing incidence of fractures in the geriatric population, the risk factors that may contraindicate traditional surgical interventions, and the complex physical and biological mechanisms by which PEMF acts to promote bone healing. The detailed analysis of the scientific evidence aims to provide an in-depth understanding of the potential of PEMF as a safe and effective alternative, contributing to the optimization of treatment strategies and improvement of patients' quality of life. Keywords: Fractures; Elderly; Osteoporosis; Pulsed Magnetic Field (PEMF); Alternative Therapies; Quality Of Life. 1. Introduction The treatment of bone fractures represents a constantly evolving field in medicine, with the aim of accelerating healing, reducing pain — minimizing the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics —, reducing postoperative complications, and improving patients' functional outcomes. With the accelerated aging of the world's population, it is estimated that by 2050 there will be more than two billion people aged 60 or over, 426 million of whom will be 80 years of age or older, which implies a significant increase in the incidence of fractures, especially in the elderly. [1.2] Fractures in this age group are often associated with osteoporosis, sarcopenia, chronic comorbidities, and a higher risk of falls, making the rehabilitation process more complex and prolonged [3]. The loss of functional independence and the increase in post-fracture mortality reinforce the need for less invasive and more effective therapeutic approaches. In this context, non-invasive therapies that favor bone healing and reduce the need for aggressive surgical interventions have gained prominence. Among these, the Pulsed Electromagnetic Field (PEMF) has emerged as a promising modality, approved by the Food and Drug Administration (FDA) of the United States and recognized by European agencies such as the European Medicines Agency (EMA), through CE certification, for the treatment of fractures with nonunion [4]. Despite the clinical World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 94 consolidation of PEMF, its cellular and molecular mechanisms are still the subject of intense investigation. In vitro and in vivo studies demonstrate that PEMF acts at multiple levels, including modulation of ion channels, especially calcium, promoting intracellular influx and activation of signaling pathways such as Ca²⁺/Calmodulin–NO–cGMP [5], in addition to the activation of adenosine A2A receptors, which stimulate cAMP production and promote osteoblastic differentiation [6]. There is also evidence of stimulation of the Want/β-catenin, MAPK/ERK, and BMP/TGF-β pathways, which are fundamental for osteogenesis and bone remodeling. [7.8] These mechanisms result in increased cell proliferation, extracellular matrix synthesis, angiogenesis, and reduced local inflammation, favoring bone regeneration. The clinical efficacy of PEMF has been demonstrated in several studies, with consolidation rates between 73% and 85% in nonunion fractures [4], significant improvement in pain, bone function and healing after 8 to 12 weeks of therapy in lower limb fractures [9], and superior results in pain and bone regeneration in cases of osteonecrosis and osteotomies [10]. The global market for PEMF devices is estimated to touch USD 784 million by 2030, with significant growth in North America and Asia Pacific. [11] Despite the growing evidence and regulatory approval, the efficacy of PEMF in the treatment of fractures, especially in vulnerable populations such as the elderly, still generates debates in the scientific community, raising the question: is the Pulsed Magnetic Field a consolidated therapeutic reality or still a promise in validation? Even with positive results, the heterogeneity in application parameters — such as frequency, intensity, and duration of exposure — still limits clinical standardization [12,13], requiring more controlled and multicenter studies [14,15]. PEMF therefore represents a non-invasive therapeutic approach with significant potential in fracture healing, especially in vulnerable populations such as the elderly. [13.16] Understanding of biophysical mechanisms [17] and ongoing clinical validation [12,14] are essential for their widespread incorporation into orthopedic practice. This review therefore aims to synthesize the current knowledge about PEMF in the treatment of fractures, detailing its efficacy [16], the epidemiological factors of fractures in the elderly [15], surgical contraindications, and the biophysical mechanisms underlying its action, with the aim of providing a solid basis for evidence-based clinical practice and directing future research in this promising field. [17] 2. Incidence of Fractures in the Elderly The increase in life expectancy of the world population has caused a significant increase in the incidence of fractures among the elderly, configuring a growing challenge for health systems and for the quality of life of affected individuals. Osteoporosis, a condition characterized by low bone mineral density and microstructural deterioration of bone tissue, is one of the main predisposing factors for fractures due to low-energy trauma in this age group [18,19]. It is estimated that one in three women and one in five men over the age of fifty will suffer osteoporotic fractures in their lifetime. [20] In addition to osteoporosis, changes in gait pattern, balance, and muscle strength due to sarcopenia increase the risk of falls, which are the main precursors of fractures in the elderly [3]. A global systematic review identified that the average prevalence of falls among the elderly is 26.5%, reaching 34.4% in Oceania and 27.9% in the Americas [21]. Among the cases of falls, approximately 19% result in fractures, and 59% occur in the domestic environment, which reinforces the need for preventive strategies aimed at home safety. [22] Fractures in the elderly have a specific anatomical distribution. Fractures of the lower limbs account for about 47% of cases, followed by upper limbs (32%), ribs and vertebrae (10%), face (8%), and hip (3%) [23]. In 2019, the global incidence of hip fractures in individuals aged 55 years and older was 681.35 per 100,000 population, with projections indicating that this number could double by 2050. [24.25] The risk of life after a hip fracture is alarming: mortality of 16% to 18% in white women and 5% to 6% in white men is estimated in the first year after the event [26]. By the age of eighty, it is estimated that one in five women will have suffered a hip fracture, and this proportion increases to one in three women by the time they reach the age of ninety [19]. In addition, only 40% of survivors regain the ability to walk independently, and 33% become fully dependent or institutionalized in the year following the fracture. [27] World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 95 Figure 1 Incidence of all fractures in adults in relation to age and gender. There is a significant increase in the incidence of fractures with advancing age, being more pronounced in women, especially after the age of fifty Risk factors for falls and fractures in the elderly are multifactorial, including advanced age, female gender, osteoporosis, polypharmacy, negative perception of health and vision, difficulty in locomotion, and lack of preventive guidance [28,29]. Early identification of these factors is essential for the implementation of effective prevention and treatment strategies, especially in view of the growing epidemiological and economic burden associated with osteoporotic fractures. This alarming increase in the incidence of fractures in the elderly and the associated severe consequences make it imperative to seek effective and less invasive therapeutic approaches, such as the Pulsed Magnetic Field, to improve clinical outcomes and quality of life in this vulnerable population. 3. Risk Factors That Contraindicate Surgical Treatment in the Elderly The decision to submit an elderly patient to a surgical intervention for the treatment of fractures is a complex process that requires a careful evaluation of the risks and benefits. Chronological age, by itself, is not the only determinant; Biological age—which reflects functional status, the presence of comorbidities, and physiological reserve—is a much more relevant factor in clinical decision-making [30]. Elderly patients often have a more complex health profile, with multiple preexisting medical conditions that can significantly increase the risk of perioperative complications and mortality, making surgery a less viable option or even contraindicated in certain scenarios. [31] Among the most critical risk factors are prolonged hospitalization or previous bed riding, which indicate basal debility, and the presence of cardiovascular diseases such as coronary artery disease, recent myocardial infarction, unstable angina, decompensated congestive heart failure, severe valvular heart diseases, and ventricular arrhythmias. These conditions increase the risk of adverse cardiac events during and after surgery [32]. Lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, also pose significant risks due to impaired respiratory function, which can be exacerbated by anesthesia and surgical stress. [33] Other medical conditions that elevate surgical risk include acute renal failure, decompensated diabetes, malnutrition, and frailty syndrome. The latter, characterized by involuntary weight loss, chronic fatigue and low muscle strength, reduces the body's ability to recover from surgical stress, even in minor procedures [34]. The presence of malignant neoplasms also contributes to frailty and worsens the prognosis. Factors such as smoking and high blood pressure, although not absolute contraindications, increase the likelihood of complications [35]. Postoperative complications in the elderly are a major concern. Studies indicate that more than 70% of postoperative deaths occur in this age group, with the main causes being respiratory infections, venous thromboembolism, urinary infections, and loss of muscle mass [31,36]. In addition to physical complications, cognitive impairment is a common and devastating sequela. Postoperative delirium and postoperative cognitive dysfunction (POCD) are conditions that World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 96 can lead to loss of independence, depression, and, in severe cases, death. General anesthesia, especially when associated with deep hypnosis, has been correlated with a higher risk of POCD. [34.37] The time until surgery is also a critical factor. Delays of more than 48 hours after hospital admission are associated with increased mortality and postoperative complications [38]. Given the complexity and risks inherent to surgical intervention in frail older adults with multiple comorbidities, the Pulsed Electromagnetic Field (PEMF) emerges not only as an alternative, but as an essential therapeutic modality to optimize the treatment of fractures, minimizing risks and promoting recovery in a population that often does not qualify for invasive procedures 4. Physical and Biological Mechanisms of the Body's Response to Pulsed Magnetic Field Fracture Treatment The interaction between low frequency pulsed electromagnetic fields (PEMF) and living tissues represents an advanced manifestation of modern biophysics. Unlike thermal or chemical stimuli, PEMF acts as a non-invasive physical agent, capable of modulating cellular and molecular processes through interaction with the electroactive constituents of biological tissues. These interactions occur by induction of electrical currents in conductive tissues, modulation of transmembrane ionic activity, and activation of mechanosensitive and electrosensitive transduction pathways [7,39,40]. From an electromagnetic point of view, PEMFs operate in frequency ranges between 1 Hz and 100 Hz, with amplitudes of up to a few militias (MT), allowing deep penetration into living tissues due to low resistance to magnetic flux. Faraday's Law of Electromagnetic Induction describes this phenomenon as the generation of electromotive force proportional to the temporal variation of the magnetic flux, expressed by: 𝐸 = 𝑑ΦB 𝑑𝑡 In the differential form, known as the Maxwell–Faraday equation, the relationship between the temporal variation of the magnetic field and the creation of rotational electric fields is described by: 𝛻 × 𝐸 󰇍 = − 𝜕𝐵 󰇍 𝜕𝑡 Figure 2 Molecular and cellular effects of PEMF on regeneration World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 97 This electromagnetic induction generates microcurrents in tissues, capable of altering the membrane potential of cells and activating voltage-gated ion channels, especially calcium channels (Ca²⁺), which trigger the Ca²⁺/CaM–NO–cGMP biochemical pathway, essential for osteogenesis. [5,7,8,43] The induced fields present a complex vector topology, with field lines spatially distributed according to the geometry of the tissue, the local conductivity and the configuration of the generating coils [44]. The orientation of magnetic flux density () and electric field (𝐵 󰇍 𝐸 󰇍 ) vectors relative to membranes, organelles, and surface proteins directly influences the activation of intracellular pathways [45,46]. This interaction can promote changes in membrane polarization, ion channel opening, and activation of cell signaling cascades. [47–49] At the molecular level, G-protein-coupled membrane receptors, such as adenosine A2A and A3, are particularly sensitive to PEMF. Its activation promotes increased cAMP, activation of protein kinase A (PKA), and inhibition of the nuclear translocation of the NF-κB factor, resulting in a reduction in the expression of inflammatory cytokines such as TNF-α and IL-1β [6,50]. This biochemical modulation favors the proliferation and differentiation of osteoblasts, inhibits osteoclastic activity, and regulates the gene expression of extracellular matrix proteins, such as type II collagen and proteoglycans. In addition, it stimulates the production of growth factors such as TGF-β, VEGF, BMP-2/4, and IGF-1, which are essential for bone and cartilage regeneration. [7,50,51] Table 1 Growth factors stimulated by PEMF Factor Main Function Effect of PEMF TGF-β Osteoblastic differentiation, collagen synthesis Increased expression and activity BMP–2/4 Induction of bone and cartilage formation Increased gene expression VEGF Angiogenesis, vascularization of bone tissue Increased production IGF-1 Cellular proliferation and differentiation Increasing local synthesis PDGF Cell proliferation and scarring Increased clearance Recent studies demonstrate that PEMF can induce epigenetic modifications in human mesenchymal stem cells, such as the acetylation of histones H3K9ac and H3K27ac in the promoters of osteogenic genes (RUNX2, SP7). These effects are mediated by reactive oxygen species (ROS) and the activation of the p38 MAPK pathway, reinforcing the non-thermal biophysical character of the stimulus and its ability to finely modulate cellular plasticity via intracellular redox sensors. [52] In addition, mechanosensitive ion channels such as Piezo1, TRP, and L-type calcium channels respond not only to mechanical strains, but also to Lorentz force applied on motile ions in the extracellular space. This force, fundamental for understanding the direct biophysical effect of PEMF on moving electric charges, is expressed by: 𝐹 = 𝑞 (𝑣 𝑥 𝐵 󰇍 ) Biological tissues can be modeled as anisotropic and heterogeneous conductors, with variable conductivity according to ionic composition, cell density, and degree of hydration. Computational modeling indicates that, even with magnetic intensities of the order of militias, the density of current generated is between 10⁻³ and 10⁻⁶ A/m², sufficient to influence ion channels without causing direct electrical excitation [53,54]. The distribution of electrical potential in tissues can be described by the anisotropic conduction equation: 𝛻 ⋅ (𝜎𝛻𝑉) = 0 Where σ represents the electrical conductivity tensor. The concept of "bio efficacy window" refers to the existence of a specific range of physical parameters (frequency, amplitude, pulse shape, duration) within which biological effects are maximized. Outside this interval, the effects dissipate or even reverse. Parate et al. (2020) demonstrated, for example, that fields of 1.5 to 2 mT per 10 minutes are ideal for chondrogenic differentiation, while prolonged exposures cancel out this effect. [55] World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 98 In the scope of biological physics, pathological states such as fractures or inflammations imply an increase in the local entropy of the biological system. Interventions such as PEMF can be interpreted as organizing forces that restore electrochemical gradients, reduce entropy, and favor homeostasis. This approach is consistent with the thermodynamics of open and self-organized systems, with the free energy of the system represented by: 𝐹 = 𝑈 − 𝑇𝑆 Where F is the free Helmholtz energy, U the internal energy, T the absolute temperature, and S the entropy of the system. In vivo studies using endochondral ossification models demonstrate that PEMF accelerates chondrogenesis, promotes cartilage removal, and favors the formation of mature bone trabeculae. The expression of mRNA for TGF-β and type II collagen increases significantly after exposure to PEMF, indicating a biochemical environment conducive to regeneration [39,56]. In addition, PEMF modulates intracellular signaling pathways such as Want/β-catenin (osteoblastic differentiation), MAPK/ERK (cell proliferation), and Notch (mesenchymal cell maturation). [6, 57] Table 2 Osteogenesis Markers Modulated by PEMF Mercader Function response to the pelf ALP (Alkaline Phosphatase) Bone mineralization Increased activity Osteocalcin Maturation of the bone matrix Increased expression Runx-2 Osteoblastic transcription factor Increased expression Type 1 collagen Main component of the bone matrix Increased synthesis Osteopenia Cellular adhesion, mineralization Increased production In summary, PEMF acts as a biophysical stimulus capable of inducing synergistic cellular and molecular responses, promoting a pro anabolic environment for bone and cartilage regeneration. By modulating intracellular signaling, extracellular matrix synthesis, and inflammatory response, PEMF accelerates the fracture healing process, offering a promising therapeutic approach, especially in cases where surgical intervention carries high risks or is contraindicated. World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 99 Figure 3 Schematic representation of the cellular and molecular mechanisms by which the Pulsed Magnetic Field (PEMF) influences bone healing. PEMF acts at several levels, from the cell membrane to gene expression, acting in the proliferation and differentiation of osteoblasts and the synthesis of components of the extracellular matrix 5. Use of PEMF in Fractures Pulsed electromagnetic field (PEMF) dosimetry is an essential component in the definition of effective therapeutic protocols for bone healing. Clinical and preclinical studies demonstrate that the intensity, frequency, and duration of PEMF sessions directly influence markers of osteogenesis, such as ALP, osteocalcin, Runx-2, and BMP-2 [57]. Protocols with intensities between approximately 0.1 and 2.8 MT (equivalent to 1–28 Gauss) and frequencies from 10 to 75 Hz are the most used in humans, with evidence of cell activation and acceleration of bone mineralization. Studies indicate that PEMF induces arteriolar vasodilation in striated muscles of rats, without interfering with systemic blood pressure or tissue temperature. This effect favors local perfusion, optimizing the supply of nutrients and osteogenic factors essential to bone regeneration, in addition to modulating the inflammatory response, creating a biochemical environment favorable to tissue regeneration. Thus, vasodilation induced by PEMF is indicated as a physiological mechanism that contributes to the angiogenic response and the acceleration of healing in fractures that are difficult to consolidate, supporting the clinical application of magnetotherapy in orthopedic contexts. [4.65] Preclinical trials in rabbits with tibial osteotomy compared 15 Hz PEMF and 1.6 MT peak with combined magnetic fields (CMF) of 76.6 Hz and up to twenty MT, including static field. Exposures ranged between 0.5 and 6 hours per day for 14 to 21 days, revealing a dose-dependent response, with longer duration associated with better biomechanical repair [62]. In a recent study with rats, 4 Hz PEMF was compared to multifrequency packets between 220 and 880 Hz (up to 10 kHz), both with an intensity of ten MT for 1 hour daily for one month. The results indicated superiority of the 4 Hz frequency in bone healing. [41] World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 100 Table 3 Clinical and experimental protocols of PEMF in fractures Study/Model Intensity Frequency Daily Sessions Total Duration Clinical outcomes Faldini et al. (2024) 2 mT (20G) 75 Hz 8 h/day 90 days 94% union vs. 69% control less pain and necrosis. Assiotis et al. (2022) ≈2 mT 10 – 50 Hz 8 h/day ≈ 5,6 months 91% healing: union at 3,3 months vs. 4,9 in control Shi et al. (2013) ND Orthopulse2 ND 8 h/day ≈ 4,5 months 77,4% healing vs. 48,1% control Cadossi et al. (2020) ND 20 Hz 30 min/day 4 weeks Union from 3rd week; pain reduced from 9 to 1 (VAS) Sales et al. (2020) 1,6 – 20 mT 15 – 76,6 Hz 0,5 – 6 h/day 14-21 days Dose-response: more expousure = higher bone strength Yildiz et al (2023, rat model) 10 mT 4 Hz vs. 220-880 Hz 1 h/day 30 days 4 hz more effective than multifrequeny. Animal models undergoing high-frequency EMPE (HF-PEMF, about four hundred pps) showed significant increase in bone formation after daily 10-minute applications for two weeks [58]. In a clinical context, the commercial Orthopulse II device was used by Shi et al. (2013) in patients with long bone fractures with delayed union, with application of 8 hours per day for approximately 4.5 months, resulting in a union rate of 77.4% compared to 48.1% in the control group. Assiotis et al. (2022) reported similar results in tibial fractures with delayed union, using approximately two mT fields for 8 hours daily for about 5.6 months. Success was observed in 91% of cases, with a reduction in the average time of marriage from 4.9 to 3.3 months. In proximal femoral fractures (Garden I–III), Faldini et al. (2024) applied two mT PEMF at 75 Hz for 8 hours a day for 90 days, obtaining a consolidation rate of 94% versus 69% in the placebo group, in addition to a lower incidence of osteonecrosis and pain. Figure 4 Application of pulsed magnetic field (PEMF) as an adjuvant therapy in the treatment of metatarsal fracture In addition to randomized controlled trials, several observational studies have documented the efficacy of pulsed electromagnetic field (PEMF) therapy in the treatment of fractures, especially in geriatric populations. In a broad retrospective analysis involving patients with fractures in the nonunion stage, it was observed that the regular use of PEMF resulted in success rates greater than 85%, with radiographic evidence of bone healing and significant pain reduction after eight weeks of treatment [63]. These findings are corroborated by investigations in elderly patients undergoing tibial osteotomies, in which the application of PEMF promoted an increase in bone mineral density and measurable functional improvement, as demonstrated by imaging tests and biochemical markers. [64] World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 101 Such evidence reinforces the role of magnetotherapy as an effective therapeutic adjuvant in the recovery of bone integrity, especially in clinical contexts of low osteogenic activity. The case studies in the elderly reinforce the clinical applicability of PEMF in vulnerable populations, with evident benefits in bone healing, pain relief, and functional recovery. In summary, clinical and preclinical studies demonstrate the significant potential of PEMF in accelerating fracture healing, especially in cases of nonunion and in high-risk populations. Optimizing treatment protocols and overcoming current limitations are crucial for PEMF to reach its full potential as a non-invasive and effective therapy in fracture management. 6. Discussion The clinical application of the Pulsed Electromagnetic Field (PEMF) in the elderly has been shown to be a promising therapeutic alternative, especially in view of the limitations imposed by comorbidities and biological fragility that often contraindicate invasive surgical interventions, but the main challenge is to adapt results obtained in the initial studies into effective therapeutic protocols in daily clinical practice. PEMF, as a non-invasive, painless, and easy-to-apply modality, offers significant benefits in bone healing, pain control and improved quality of life in geriatric patients with fractures. Figure 5 Third metatarsal fracture submitted to conservative treatment with immobilization associated with PEMF. With this therapeutic combination, there was a reduction in the need for NSAIDs, in addition to a reduction in the time required to observe radiographic consolidation In addition to bone healing, PEMF has demonstrated positive effects on cartilaginous regeneration and bone edema reduction and is useful in cases of osteonecrosis and complex fractures. World Journal of Advanced Research and Reviews, 2025, 28(02), 093–110 108 [30] Zhou, Y., Zhang, Y., Lu, P., et al. (2022). Treatment strategies for non-displaced femoral neck fractures in the elderly. Arthroplasty, 4, Article 8. https://doi.org/10.1186/s42836-022-00111-0 [31] Zhang, H., Ma, L., and Yu, X. (2025). 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