Pulsed electromagnetic fields modulate bone metabolism via RANKL/OPG and Wnt/β-catenin pathways in women with postmenopausal osteoporosis: A pilot study

Catalano, Antonino; Loddo, Saverio; Bellone, Federica; Pecora, Carmelo; Lasco, Antonino; Morabito, Nunziata

doi:10.1016/j.bone.2018.07.010

Cited by 43 publications

(45 citation statements)

References 36 publications

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“…However, there are also several other reports showing ELF-PEMF inhibitory effects on osteoclastogenesis [66][67][68]. He et al suggest that ELF-PEMF suppressive effects are mediated by endocrine effects of osteoblasts [67], a hypothesis supported by several other studies [61,[69][70][71][72]. While Wang et al proposed that regulation of osteoclastogenesis is strongly dependent on the intensity of the applied ELF-PEMF [73], Lei et al showed bone metabolic ELF-PEMF effects in osteoporotic (ovariectomized) mice which strongly depended on the frequency range applied [74].…”

Section: Elf-pemf Effects On Bone Cell Functionmentioning

confidence: 85%

Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery

Ehnert

Schröter

Aspera-Werz

et al. 2019

JCM

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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.

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Section: Elf-pemf Effects On Bone Cell Functionmentioning

confidence: 85%

Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery

Ehnert

Schröter

Aspera-Werz

et al. 2019

JCM

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“…The roles of the different Wnt ligands in bone homeostasis and bone diseases are not yet fully understood. There have been many clinical trials and experimental studies reporting that PEMFs modulate bone metabolism through the Wnt/β‐catenin pathway . However, few researchers have investigated the Wnt ligands involved in the process, except for Wnt1 and Wnt3a .…”

Section: Discussionmentioning

confidence: 99%

“…There have been many clinical trials and experimental studies reporting that PEMFs modulate bone metabolism through the Wnt/bcatenin pathway. (34)(35)(36)(37)(38)(39)(40)(41) However, few researchers have investigated the Wnt ligands involved in the process, except for Wnt1 and Wnt3a. (42)(43)(44)(45)(46)(47) In the present study, we did not find increased expression of Wnt3a in the bone samples of rats and in vitro cultured osteoblasts treated by SEMFs, but found the significantly increased expression of Wnt10b.…”

Section: Discussionmentioning

confidence: 99%

Sinusoidal Electromagnetic Fields Increase Peak Bone Mass in Rats by Activating Wnt10b/β-Catenin in Primary Cilia of Osteoblasts

Zhou

Gao

Zhu

et al. 2019

Journal of Bone and Mineral Research

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Extremely low‐frequency electromagnetic fields have been considered a potential candidate for the prevention and treatment of osteoporosis; however, their action mechanism and optimal magnetic flux density (intensity) parameter are still elusive. The present study found that 50‐Hz sinusoidal electromagnetic fields (SEMFs) at 1.8 mT increased the peak bone mass of young rats by increasing bone formation. Gene array expression studies with femoral bone samples showed that SEMFs increased the expression levels of collagen‐1α1 and Wnt10b, a critical ligand of the osteogenic Wnt/β‐catenin pathway. Consistently, SEMFs promoted osteogenic differentiation and maturation of rat calvarial osteoblasts (ROBs) in vitro through activating the Wnt10b/β‐catenin pathway. This osteogenesis‐promoting effect of SEMFs via Wnt10b/β‐catenin signaling was found to depend on the functional integrity of primary cilia in osteoblasts. When the primary cilia were abrogated by small interfering RNA (siRNA) targeting IFT88, the ability of SEMFs to promote the osteogenic differentiation of ROBs through activating Wnt10b/β‐catenin signaling was blocked. Although the knockdown of Wnt10b expression with RNA interference had no effect on primary cilia, it significantly suppressed the promoting effect of SEMFs on osteoblastic differentiation/maturation. Wnt10b was normally localized at the bases of primary cilia, but it disappeared (or was released) from the cilia upon SEMF treatment. Interestingly, primary cilia were elongated to different degrees by different intensities of 50‐Hz SEMFs, with the window effect observed at 1.8 mT, and the expression level of Wnt10b increased in accord with the lengths of primary cilia. These results indicate that 50‐Hz 1.8‐mT SEMFs increase the peak bone mass of growing rats by promoting osteogenic differentiation/maturation of osteoblasts, which is mediated, at least in part, by Wnt10b at the primary cilia and the subsequent activation of Wnt/β‐catenin signaling. © 2019 American Society for Bone and Mineral Research.

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“…Recent experimental studies have demonstrated that PEMF partially preserved bone mass and strength in hindlimb‐unloaded, ovariectomized, or diabetic animals by primarily promoting bone formation . Clinical studies also reveal that PEMF increased bone mass in postmenopausal women . However, the potential effects of PEMF on age‐related bone loss have never been investigated previously.…”

Section: Introductionmentioning

confidence: 99%

“…[27][28][29] Clinical studies also reveal that PEMF increased bone mass in postmenopausal women. 30,31 However, the potential effects of PEMF on age-related bone loss have never been investigated previously. More importantly, whether PEMF coupled with exogenous mechanical signals can produce more profound osteogenic effects than single stimulation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Differential skeletal response in adult and aged rats to independent and combinatorial stimulation with pulsed electromagnetic fields and mechanical vibration

et al. 2019

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Pulsed electromagnetic fields (PEMFs) and whole‐body vibration (WBV) are proved to partially preserve bone mass/strength in hindlimb‐unloaded and ovariectomized animals. However, the potential age‐dependent skeletal response to either PEMF or WBV has not been fully investigated. Moreover, whether the coupled “mechano‐electro‐magnetic” signals can induce greater osteogenic potential than single stimulation remains unknown. Herein, 5‐month‐old or 20‐month‐old rats were assigned to the Control, PEMF, WBV, and PEMF + WBV groups. After 8‐week treatment, single PEMF/WBV enhanced bone mass, strength, and anabolism in 5‐month‐old rats, but not in 20‐month‐old rats. PEMF + WBV induced greater increase of bone quantity, quality, and anabolism than single PEMF/WBV in young adult rats. PEMF + WBV also inhibited bone loss in elderly rats by primarily improving osteoblast and osteocyte activity, but had no effects on bone resorption. PEMF + WBV upregulated the expression of various canonical Wnt ligands and downstream molecules (p‐GSK‐3β and β‐catenin), but had no impacts on noncanonical Wnt5a expression in aged skeleton, revealing the potential involvement of canonical Wnt signaling in bone anabolism of PEMF + WBV. This study not only reveals much weaker responsiveness of aged skeleton to single PEMF/WBV relative to young adult skeleton, but also presents a novel noninvasive approach based on combinatorial treatment with PEMF + WBV for improving bone health and preserving bone quantity/quality (especially for age‐related osteoporosis) with stronger anabolic effects.

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Pulsed electromagnetic fields modulate bone metabolism via RANKL/OPG and Wnt/β-catenin pathways in women with postmenopausal osteoporosis: A pilot study

Cited by 43 publications

References 36 publications

Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery

Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery

Sinusoidal Electromagnetic Fields Increase Peak Bone Mass in Rats by Activating Wnt10b/β-Catenin in Primary Cilia of Osteoblasts

Differential skeletal response in adult and aged rats to independent and combinatorial stimulation with pulsed electromagnetic fields and mechanical vibration

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