Case report Myoglobinuria in two patients with Duchenne muscular dystrophy after treatment with zoledronate: a case-report and call for caution Anton Ivanyuk a, * , Nuria García Segarra b , Thierry Buclin a , Andrea Klein c, d , David Jacquier c , Christopher J. Newman c , Clemens Bloetzer c, e a Service of Clinical Pharmacology, Lausanne University Hospital (CHUV), Bugnon 17, 1011 Lausanne, Switzerland b Center for Molecular Diseases, Division of Genetic Medicine, Lausanne University Hospital (CHUV), Pierre-Decker 2, 1011 Lausanne, Switzerland c Paediatric Neurology and Neurorehabilitation Unit, Lausanne University Hospital (CHUV), Pierre-Decker 5, 1011 Lausanne, Switzerland d Pediatric Neurology, University Children’s Hospital Basel, UKBB, and Inselspital Bern, Switzerland e Institute of Social and Preventive Medicine, University of Bern, Switzerland Abstract Rhabdomyolysis with myoglobinuria is a recognized complication of dystrophinopathies. It can be triggered by infections, exercise or volatile anesthetics. To our knowledge, it has never been reported in boys with Duchenne muscular dystrophy (DMD) after the administration of bisphosphonates. We report two patients with DMD who presented an apparent transient rhabdomyolysis with myoglobinuria after zoledronate administration. Possible mechanisms could involve hypophosphatemia, a known dose-dependent side effect of bisphosphonates, and/or direct myotoxicity of biphosphonates. Physicians and families should be aware of rhabdomyolysis with myoglobinuria as a potential uncommon side effect of bisphosphonates in DMD, in particular of zoledronate. . Keywords: Duchenne muscular dystrophy; myoglobinuria; bisphosphonates; zoledronate. 1. Introduction Duchenne muscular dystrophy (DMD) is an X-linked pro- gressive myopathy due to mutations in the dystrophin gene, affecting one in every 3600–10,000 live male births [1,2]. Boys with DMD typically present with delayed motor mile- stones and muscle weakness, they progress to loss of am- bulation around their teens, and respiratory and heart failure during the second decade. Corticosteroids remain the standard supportive therapy for DMD even though new treatments re- cently emerged [3–6]. Along with other risk factors that are present in DMD such as progressive weakness, immobility and delayed puberty, chronic corticosteroid therapy increases the risk of low bone mineral density, exposing these patients to fractures, pain and decreased quality of life. Little data is available to guide best practice for bone health management * Corresponding author. Fax number: 0041 21 314 35 95 E-mail address: anton.ivanyuk@chuv.ch (A. Ivanyuk). in DMD [7]. However, a consensus exists on the use of bis- phosphonates to improve bone mineral density in cases of fractures or bone pain [3,8]. 2. Case report Patient 1 is a 14-year-old boy with DMD due to a dele- tion of exon 50. He was diagnosed at 5 years; corticosteroids were initiated at 9 years old only, due to parents’ concerns about side-effects. Independent walking was lost at 13 years. Bisphosphonates were proposed at 13 years because of in- tractable bone pain and low bone mineral density on DEXA scan (hip Z-score –3.7 SD, lumbar spine Z-score –2.1 SD). A first infusion of zoledronate (0.04 mg/kg) was well toler- ated. A second infusion at the same dose was administrated six months later. Two days after this second infusion, the patient developed flu-like symptoms with diffuse myalgia, vomiting, and dark brown urine. No urine or blood control was performed during the acute phase, since the apparent Published in final edited form as: Neuromuscul Disord. 2018 Oct;28(10):865-867. doi: 10.1016/j.nmd.2018.08.004. source: https://doi.org/10.7892/boris.120038 | downloaded: 30.6.2020