Pulsed Electromagnetic Field Treatment Enhances Healing Callus Biomechanical Properties in an Animal Model of Osteoporotic Fracture Caroline Androjna, Brian Fort, Maciej Zborowski, and Ronald J. Midura* Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio Delayed bone healing has been noted in osteoporosis patients and in the ovariectomized (OVX) rat model of estrogen-depletion osteopenia. Pulsed electromagnetic field (PEMF) devices are clinically approved as an adjunct to cervical fusion surgery in patients at high risk for non-fusion and for the treatment of fracture non-unions. These bone growth stimulating devices also accelerate the healing of fresh fracture repair in skeletally mature normal rats but have not been tested for efficacy to accelerate and/or enhance the delayed bone repair process in OVX rats. The current study tested the hypothesis that daily PEMF treatments would improve the fracture healing response in skeletally mature OVX rats. By 6 weeks of healing, PEMF treatments resulted in improved hard callus elastic modulus across fibula fractures normalizing the healing process in OVX rats with respect to this mechanical property. Radiographic evidence showed an improved hard callus bridging across fibula fractures in OVX rats treated with PEMF as compared to sham treatments. These findings provide a scientific rationale for investigating whether PEMF might improve bone-healing responses in at-risk osteoporotic patients. Bioelectromagnetics 35:396–405, 2014. © 2014 Wiley Periodicals, Inc. Key words: PEMF; bone; fracture repair; osteoporosis; delayed healing INTRODUCTION Primary osteoporosis is a metabolic disease stemming from estrogen depletion during menopause, which results in progressive decreases in bone mass, bone mineral density, and bone micro-architecture [Khosla et al., 2012]. These structural alterations in bone tissue lead a decline in bone strength and confer a higher risk of fracture under normal skeletal loads (“fragility fractures”) and an increased severity of fractures after trauma [Armas and Recker, 2012]. Moreover, estrogen manifests direct positive effects on bone-forming osteoblasts that maintain bone formation activities and a chronic loss of estrogen in menopausal women is associated with a decline in bone formation activities [Khosla et al., 2012]. Primary osteoporosis has been known to delay fracture healing in humans [Giannoudis et al., 2007] and several well-controlled, pre-clinical fracture healing studies using a conventional ovariectomized (OVX) rat model of estrogen-depletion osteopenia confirm this outcome [Walsh et al., 1997; Kubo et al., 1999; Meyer et al., 2001; Wang et al., 2005; Yingjie et al., 2007; McCann et al., 2008]. While these studies employed different open or closed fracture models in different leg bones and used different means to stabilize the fracture sites, a consensus opinion still emerged. These investigations all concluded that bone healing in skeletally mature OVX rats was delayed when compared to age-matched, normal rats. Specific devices generating pulsed electromag- netic fields (PEMFs) are approved by the U.S. Food and Drug Administration as non-pharmacological therapies for human bone growth stimulation (“class III devices”). Some are approved as an adjunct to cervical fusion surgery in patients at high risk for non- fusion and for the treatment of fracture non-unions [Hinsenkamp et al., 1985; Griffin et al., 2008]. PEMF treatments have also been reported to accelerate the healing of fresh fracture repair in skeletally mature normal rats [Hinsenkamp et al., 1978; Grace et al., Grant sponsor: Orthofix (Lewisville, TX). *Correspondence to: Ronald J. Midura, Department of Biomedical Engineering/ND20, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195. E-mail: midurar@ccf.org Received for review 16 October 2013; Accepted 11 March 2014 DOI: 10.1002/bem.21855 Published online 24 April 2014 in Wiley Online Library (wileyonlinelibrary.com). Bioelectromagnetics 35:396^405 (2014) ß 2014 Wiley Periodicals, Inc.