70 Global Journal of Oral Science, 2018, 4, 70-81 E-ISSN-2414-2050 © 2018 Global Journal of Oral Science In vivo Experimental Models to Investigate EMF Effects on Bone C. Galli 1,* , M. Colangelo 2 , G. Pedrazzi 3 , and S. Guizzardi 2 1 Department Of Medicine and Surgery, University of Parma, 2 Department Of Medicine and Surgery, Histology and Embryology Lab, University of Parma, 3 Department Of Medicine and Surgery, Neuroscience Unit, University of Parma, Via Volturno 39, 43126 Parma, Italy Abstract: Electromagnetic fields (EMFs) have long been investigated as both a source of health concern and a possible therapeutic tool for several disease conditions, including bone loss and bone regenerative needs. A broad literature is available on the effects of EMFs on bone, both with clinical and pre-clinical models, but the great heterogeneity of settings, delivery modalities and results are a potent reminder of the lack of consensus that is still surrounding this technology and marring its clinical applications. The present review therefore assessed the available animal studies that investigated the effects of sinusoidal and pulsed EMFs to treat bone conditions or to improve bone healing under different experimental conditions, to identify possible areas where future research should focus to fill the knowledge gaps that still impair the clinical use of EMFs. Keywords: Electromagnetic fields, Animal models, Bone, SEMF, PEMF. INTRODUCTION The use of animal models has been a cornerstone of research to investigate the biological effects of electromagnetic fields in living organisms and mostly responds to two types of scientific questions. First and foremost, animal models allow investigators to perform in-depth analysis of a biological system and therefore obtain more data and cleaner results as the genetic background of the organisms and the experimental conditions used are more easily controlled. On the other hand, animal models allow to screen more treatments, and establish better settings, materials and conditions that can be then translated to the clinical field. As electromagnetic fields (EMFs) have long been proposed as a clinical approach to several pathological and surgical conditions but have thus far failed to become part of the clinical routine, the purpose of the present review is to assess what experimental models have been used in bone research and whether data quality can be increased by covering thus far little explored areas of research. ELECTROMAGNETIC FIELDS Electromagnetic fields are a common element in our everyday life, as electrical appliances, wirings, cell phones and Wi-Fi networks are ubiquitous in our surrounding environment. Besides artificial electromagnetic fields, earth itself generates a weak but pervasive magnetic field thanks to its iron core of molten metals [1]. An electromagnetic field (EMF) is * Address correspondence to this author at the University of Parma, Dep. Of Medicine and Surgery, Via Gramsci 14, 43126 Parma, Italy; Tel: +39 0521 906740; E-mail: carlo.galli@unipr.it generated by the flow of an electric current and possesses therefore two coupled components: an electric field and a magnetic field. An electric current can generate a magnetic field, and a magnetic field can, in turn, induce an electric current, a physical principle we are all aware of, since the invention of dynamos, and which has profound significance to understand the effects of EMFs in biological systems. EMFs can be imagined as waves that have a certain frequency, expressed in Hertz [Hz] (cycles/second), and intensity, measured in Tesla [T], or, nowadays more rarely, in Gauss (1 G = 10 -4 T) [2]. Based on their frequency, and therefore their intrinsic energy, EMFs can be distinguished into ionizing or non-ionizing radiations, i.e. radiations capable or incapable to remove electrons from atoms, thus creating ions (UVC or gamma rays are known examples of ionizing radiations). Although ionizing radiations have long been known to affect living organisms, mostly harming them to the point that these are often used as sterilization tools [3, 4], research has shown that non-ionizing radiations can still strongly interact with biological tissues and cells [5, 6]. EMF AND HEALTH The idea that EMFs could interact with cells and therefore tissues and organisms dates back to the beginning of the XX century, as it was known that cells possess and are surrounded by electrical charges and that ions have an important role in cell physiology [7]. A rich literature [8, 9, 18-20, 10-17] has been published exploring the effects of electric and magnetic fields on plants and animals and the first evidence of possibly harmful effects of non-ionizing radiations dates back to the end of the ‘70s, as artificial, environmental EMFs