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

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          Abstract

          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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          From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.

          Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert ss-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor gamma by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the "estrogen-centric" account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them.
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            Factors affecting therapeutic compliance: A review from the patient’s perspective

            Objective To explore and evaluate the most common factors causing therapeutic non-compliance. Methods A qualitative review was undertaken by a literature search of the Medline database from 1970 to 2005 to identify studies evaluating the factors contributing to therapeutic non-compliance. Results A total of 102 articles was retrieved and used in the review from the 2095 articles identified by the literature review process. From the literature review, it would appear that the definition of therapeutic compliance is adequately resolved. The preliminary evaluation revealed a number of factors that contributed to therapeutic non-compliance. These factors could be categorized to patient-centered factors, therapy-related factors, social and economic factors, healthcare system factors, and disease factors. For some of these factors, the impact on compliance was not unequivocal, but for other factors, the impact was inconsistent and contradictory. Conclusion There are numerous studies on therapeutic noncompliance over the years. The factors related to compliance may be better categorized as “soft” and “hard” factors as the approach in countering their effects may differ. The review also highlights that the interaction of the various factors has not been studied systematically. Future studies need to address this interaction issue, as this may be crucial to reducing the level of non-compliance in general, and to enhancing the possibility of achieving the desired healthcare outcomes.
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              Pain assessment.

              Pain usually is the major complaint of patients with problems of the back, thus making pain evaluation a fundamental requisite in the outcome assessment in spinal surgery. Pain intensity, pain-related disability, pain duration and pain affect are the aspects that define pain and its effects. For each of these aspects, different assessment instruments exist and are discussed in terms of advantages and disadvantages. Risk factors for the development of chronic pain have been a major topic in pain research in the past two decades. Now, it has been realised that psychological and psychosocial factors may substantially influence pain perception in patients with chronic pain and thus may influence the surgical outcome. With this background, pain acceptance, pain tolerance and pain-related anxiety as factors influencing coping strategies are discussed. Finally, a recommendation for a minimum as well as for a more comprehensive pain assessment is given.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                20 November 2019
                December 2019
                : 8
                : 12
                : 2028
                Affiliations
                [1 ]Siegfried Weller Institute for Trauma Research, Depterment of Trauma and Reconstructive Surgery, BG Unfallklinik Tübingen, Eberhard Karls Universität Tübingen, D-72076 Tübingen, Germany; sschroeter@ 123456bgu-tuebingen.de (S.S.); rominaaspera@ 123456hotmail.com (R.H.A.-W.); weisler@ 123456bgu-tuebingen.de (W.E.); andreas.nuessler@ 123456gmail.com (A.K.N.)
                [2 ]Sachtleben GmbH, Hamburg, Haus Spectrum am UKE, Martinistraße 64, D-20251 Hamburg, Germany; falldorf@ 123456citresearch.de (K.F.); ronniger@ 123456citresearch.de (M.R.)
                Author notes
                Author information
                https://orcid.org/0000-0003-4347-1702
                https://orcid.org/0000-0002-6666-6791
                Article
                jcm-08-02028
                10.3390/jcm8122028
                6947624
                31756999
                b9d4a6a0-0eb0-455f-9ecd-50bc9f86bdd4
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 September 2019
                : 18 November 2019
                Categories
                Review

                extremely low frequency pulsed electromagnetic fields (elf-pemf),bone regeneration,fracture healing,spinal fusion,osteoporosis,bone mineral density,osteoarthritis,pain,bone cells

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