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Vitamin D deficiency, circulating levels lower than 15 ng/ml, is an epidemic disease worldwide with more than a billion people suffering of it in the beginning of the 21-century. Besides its impact on mineral and bone metabolism, these low vitamin D levels are also associated with a diversity of non-skeletal complications, among them cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, tuberculosis, and immune system dysfunction. Chronic Kidney Disease is also a very common disease, affecting more than 10% of the world population, ranging from stage 1 to stage 5 before dialysis. Approximately 1% of the population in industrialized countries is affected by end-stage renal disease (ESRD), needing a renal replacement therapy either hemodialysis or peritoneal dialysis, and ultimately by renal transplantation. Those CKD patients are more susceptible to exhibit reduced vitamin D stocks. Consequently, more than eighty percent of CKD patients have either insufficient or deficient vitamin D levels for multiple reasons.
We present to our readers the proceedings of the Second International Workshop on Phosphate. A short account of the history of the effort led to the Phosphate Workshops is appro priate and can be of interest to the reader. The idea for Phosphate Workshops was born in the early days of November, 1974. One of us (S. G. M. ) suggested the thought to a group of scientists gathered for a luncheon in one of the attrac tive small restaurants in Weisbaden, Germany. The purpose of the workshop was to bring together interested scientists to discuss the newer developments and the recent advances in the field of phosphate metabolism and the other related minerals. An Organizing Committee made of Shaul G. Massry (USA), Louis V. Avioli (USA), Philippe Bordier (France), Herbert Fleisch (Switzerland), and Eduardo Slatopolsky (USA) was formed. The First Workshop was held in Paris during June 5-6, 1975 and was hosted by Dr. Philippe Bordier. Its proceeding was already published. The Second Workshop took place in Heidelberg during June 28-30, 1976 and was hosted by Dr. Eberhard Ritz. Both of these workshops were extremely successful scientific endeavors, and the need for them was demonstrated by the great interest they generated among the scientific community. The Or ganizing Committee, therefore, decided to continue with the tradi tion to hold additional Workshops annually or every other year.
This volume represents the first attempt to present in one place the clinical syndromes and the pathophysiologic basis for the "resistance states" to each of the classes of steroid hormones. Glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone and vitamin D have widely diverse roles ranging from the control of homeostasis to reproduction and bone formation. They are similar in that they share a chemical structure and that their action is in the cell nucleus where they induce transcription of specific genes leading to synthesis of function-specific proteins. Clinical syndromes of steroid hormone resistance to androgens (complete and partial testicular feminization), aldosterone (pseudo hypoaldosteronism) and vitamin D (vitamin D-dependent rickets type II) have been known for many years. Progesterone and glucocorticoid resistance syndromes have been described only recently. Resistance to estrogens has not been reported in man or in animals. It is hoped that a detailed reexamination of what is known about each of these conditions at the clinical and molecular levels will enhance our understanding of the function of these hormones and their mechanisms of action. New insight and research initiatives should result. G.P. Chrousos D.L. Loriaus M.B. Lipsett vii ACKNOWLEDGMENTS The contents of this volume are based in part on the proceedings of an International Conference held in Bethesda in the summer of 1984. This conference was sponsored by the National Institute of Child Health and Human Development, Bethesda, Maryland.
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The present book contains the Proceedings of a two day Symposium on Uremic Toxins organized at the University of Ghent in Belgium. A series of guest lectures, free communications and posters have been presented. An international audience of 163 scientists from 16 nationalities listened to and discussed extensively a spectrum of topics brought forward by colleagues and researchers who worked for many years in the field of Uremic Toxins. There is a striking contrast between all the new dialysis strategies available in the work to "clean" the uremic patients and the almost non-progression of our knowledge on uremic toxins in the past decade. In this sense the symposium was felt by all participants as a new start for the research in the biochemical field of the definition of uremia. If the present volume would stimulate new work in this field in order to define uremia, or identify the uremic toxins, the purpose of the organizers would be maximally fulfilled.
EDITOR-IN-CHIEF: Clifford J. Rosen, M.D., Maine Medical Center Research Institute, Scarborough, Maine SENIOR ASSOCIATE EDITORS: Juliet E. Compston, M.D., FRCP, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom Jane B. Lian, Ph.D., University of Massachusetts Medical School, Worcester, Massachusetts This comprehensive yet concise handbook is an indispensable reference for the many clinicians who see patients with disorders of bone formation, metabolic bone diseases, or disorders of stone formation. It is also a crucial tool for researchers, students, and all other professionals working in the bone field. In a format designed for quick reference, it provides complete information on the symptoms, pathophysiology, diagnosis, and treatment of all common and rare bone and mineral disorders. New in this edition: detailed coverage of osteonecrosis of the jaw, more in-depth coverage of cancer and bone including new approaches to pathogenesis, diagnosis, and treatment; new approaches to anabolic therapy of osteoporosis; the latest research on Vitamin D; expanded coverage of international topics; more on the genetics of bone mass; and newer imaging techniques for the skeleton. In addition, this edition features a free, online-only appendix of medicines used to treat bone disorders and their availability around the world.
This comprehensive manual covers all aspects of the prevention, diagnosis and management of osteoporosis, offering an upbeat and optimistic assessment of what can be achieved. While scientifically based, the book provides easy-to-follow guidelines for lifelong maintenance of skeletal structure and function. It deals with everything from the basic physiology of bone and mineral metabolism to the diagnostic utility of radiologic imaging and specialized tests and current treatment recommendations, including for fracture management. The relationship of osteoporosis to a variety of other disorders is also thoroughly explored and elucidated. Osteoporosis represents a global threat because every human being is vulnerable to it as time passes. The authors point out the enormous scale of the problem in terms of the human suffering, morbidity, and mortality on the one hand and the associated astronomical national and global costs on the other. Osteoporosis is preventable, and every doctor in every medical discipline can contribute to this goal. And though prevention is better than cure, it is never too late for effective therapy, as outlined in this book. Bone is every doctorʼs and every bodyʼs business!
The Nutrition and Health series of books has as an overriding mission to provide health professionals with texts that are considered essential because each includes: a synthesis of the state of the science; timely, in-depth reviews by the leading researchers in their respective fields; extensive, up-to-date fully annotated reference lists; a detailed index; relevant tables and figures; identification of paradigm shifts and the consequences; of information between chapters, but targeted, inter-chapter refer virtually no overlap rals, suggestions of areas for future research; and balanced, data-driven answers to patient questions that are based on the totality of evidence rather than the findings of any single study. The series volumes are not the outcome of a symposium. Rather, each editor has the potential to examine a chosen area with a broad perspective, both in subject matter as well as in the choice of chapter authors. The international perspective, especially with regard to public health initiatives, is emphasized where appropriate. The editors, whose training is both research and practice oriented, have the opportunity to develop a primary objective for their book, define the scope and focus, and then invite the leading authori ties from around the world to be part of their initiative. The authors are encouraged to provide an overview of the field, discuss their own research, and relate the research de findings to potential human health consequences.
Hypercalcemia is the most common life-threatening metabolic disorder associated with cancer. The pathophysiological, epidemiological and clinical aspects of hypercalcemia of malignancy are presented in this issue, with a focus on the recently discovered humoral factor responsible for the development of hypercalcemia. With a better understanding of the pathophysiology of this condition and the development of new potent drugs, capable of inhibiting bone resorption, especially bisphosphonates, the clinician will be more successful in correcting hypercalcemia in the great majority of patients.
Because diseases of the bone are often less acute and less lifethreatening than dis eases of the circulatory system, gastrointestinal tract, kidney, liver, and the nervous system, they have received a disproportionately smaller amount of attention in the medical world. With the average increasing life span of man as a result of improve ments in modern medicine, espe~ially in the pediatric field, the seriousness of many metabolic bone diseases has indeed become more obvious. In addition, other improvements in medicine, such as hemodialysis for the preservation of renal failure patients, have permitted the development of other consequences of diseased kidneys, one of which is the appearance of renal osteodystrophy. Finally, the appearance of several genetic disorders in the area of metabolic bone disease has been underscored by the solution of other pediatric diseas~s of much more serious consequences. These emerging problems all suggest that much remains to be learned concerning the sys temic control of bone, both as a structural organ and as a reservoir for the important elements of calcium and phosphorus so essential for the support of life in complex multicellular organisms of which man is the most important. As will be demonstrated in the historical portion of this manuscript, the existence of the three most important humoral factors regulating bone metabolism and func tion are now known.