| Biography | |
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 Prof. Gordon L Klein University of Texas Medical Branch, USA |
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| Title: Preventing Bone Resorption in Burns Spares Muscle Wasting | |
| Abstract: Bone resorption caused by inflammation releases transforming growth factor-beta (TGF-beta) from bone matrix, resulting in paracrine catabolic effects on skeletal muscle in two distinct conditions: cancer metastatic to bone and pediatric burn injury. In bone metastases the damage appears to be caused by oxidative stress that damages the ryanodine receptor in muscle, leading to calcium leakage and muscle weakness. In pediatric burns, TGF-beta release from bone appears to depress the phosphorylation of the Akt/mTor protein anabolic pathway and increase activity of the ubiquitin ligase catabolic pathway. While similar analyses were not performed in these two clinical settings, muscle wasting in both was prevented by the use of bisphosphonates, implicating the bone as the source of catabolic activity in muscle. Inasmuch as these two conditions involve distinct patient groups, it is possible that bone release of TGF-beta is a universal means by which bone may control muscle mass. Thus in these two conditions, bisphosphonates can successfully prevent muscle wasting, but what happens in other hyper-resorptive conditions? We know that in some conditions, such as critical illness myopathy, loss of muscle and bone appear linked. Studies on a rat model of pharmacologic immobilization and mechanical ventilation show a direct correlation between time and magnitude of trabecular bone and muscle loss as well as trabecular bone and myosin loss (Gugala Z et al J Orthop Res 2022),although bisphosphonates have not been used to determine if muscle wasting can be prevented by reducing bone resorption in this model. Further studies are indicated to determine if other conditions can also be treated in this way, whether there is a threshhold effect for bone resorption release of TGF-beta, whether factors released by bone are always in the same quantity and proportion or whether these are modulated by metabolic conditions of other tissues. Answers to these questions may broaden the use of anti-resorptive agents to treat a larger number of conditions. | |
| Biography: I am currently Senior Scientist and Adjunct Professor of Orthopaedic Surgery at the University of Texas Medical Branch in Galveston, a position I have held since July 2010. My current interest is in muscle- I currently am Editor-in-Chief of the journal Endocrines, MDPI, Basel, section on Parathyroid disease, mineral metabolism and bone function, and Associate Editor of Frontiers in Endocrinology, section on Bone Research, Frontiers Publications, Lausanne. I have an AB degree from Columbia University followed by post-graduate study in Investigative Medicine at Cambridge University and an MD degree from the Albert Einstein College of Medicine in New York. I completed a residency in pediatrics at Stanford University, and post-doctoral fellowships in pediatric nutrition at Johns Hopkins and pediatric gastroenterology at the University of California, Los Angeles. I have been a consultant to the United States Food and Drug Administration on the effects of aluminum on bone and liver, and its contamination of formulas used for intravenous nutrition of hospitalized adults and children. I have also been a member of the Executive Committee of Revision of the United States Pharmacopeia, and several panels and working groups of the National Institutes of Health, in particular the National Institute of Child Health and Human Development. I have spent 30 years studying the effect of burn injury on bone and muscle metabolism and have lectured around the world on this topic. I have served on the Editorial Boards of the Journal of Bone and Mineral Research (2008-2012), the Journal of Bone and Mineral Metabolism (2006-present), Osteoporosis and Sarcopenia (2015-present), Biological Trace Element Research (2020-present), and the International Journal of Molecular Sciences (2020-present). In addition, I have guest edited special issues of Seminars in Cell and Developmental Biology (2016) and Frontiers in Endocrinology, Bone Research (2019-2022). My contributions to science have included the discovery of intravenous nutrition-induced aluminum bone and liver diseases, identification of the sources of aluminum contamination of intravenous solutions as coming from impurities in calcium and phosphate salts, albumin and heparin, as well as a previous source of protein in those feeding solutions, casein hydrolysate. I reported the first description of bone loss following burn injury and its appropriate treatment with anti-resorptive agents such as bisphosphonates, the failure of burned skin to produce normal amounts of vitamin D from ultraviolet irradiation leading to progressive vitamin D deficiency, and most recently the preservation of muscle mass and strength in burn injury following treatment with bisphosphonates to prevent post-burn bone resorption. I am a Fellow of the Royal Society of Medicine, London (2017), a Fellow of the American Gastroenterological Association (2011), and an Inaugural Fellow of the American Society for Bone and Mineral Research (2018). In addition I am an Emeritus Member of the American Pediatric Society and the Society for Pediatric Research. | |
