Twenty years have passed since I became a professor in the First Department of Pathology, Hiroshima University School of Medicine. It is my great pleas ure that Molecular Pathology o[ Gastroenterological Cancer-Application to Clinical Practice has been published by Springer-Verlag Tokyo to commemo rate the 20th anniversary of my professorship. Seeing the academic achievements of our department during these 20 years, I am confident that we could establish a department of oncology to research the pathogenesis of human cancer through systemic application of a variety of molecular techniques. We have demonstrated that the develop me nt and progression of esophageal, gastric, and colon cancer require mul tiple alterations affecting DNA mismatch repair genes, oncogenes, and tumorsuppressor genes, and that common and uncommon genetic changes exist for esophageal, gastric, and colorectal carcinomas. In addition to these genetic changes, the majority of gastrointestinal cancers express telomerase activity, with overexpression of telomerase RNA, indicating a powerful addi tional tool for early detection of gastrointestinal cancer. By transferring these basic observations to the clinic, we now are able to make accurate cancer diagnoses, thus determing the grade of malignancy and patient prognosis. We also can identify patients at high risk for developing cancer and create new therapeutic approaches. In fact, we have routinely implemented a new molecular diagnosis strategy at the Hiroshima City Medi cal Association Clinical Laboratory since August 1993.

This book is designed primarily for anatomic pathologists to facilitate their task of accurately diagnosing embryos and fetuses. A detailed examination of the products of spontaneous and induced abortions is necessary for accurate genetic counseling and for establishing the risk for specific abnormalities or another spontaneous pregnancy loss in the future. The growing interest in the defects of early development reflects the profound change in general life-style. In the past, spontaneous abortions were considered a common, usually sporadic event in a patient's reproductive history. Only reassurance and encour agement were given to the patient and scant attention was paid to the detailed pathology of the abortus. Nowadays, however, as a result of reliable methods of contraception and of the availability of reliable prenatal diagnosis for chromosome abnormalities more frequent in advanced maternal age, significant numbers of parents plan to have pregnan cies later in their reproductive life. Consequently, in a case of spontaneous abortion, the question of "cause" and of "future risk" of recurrence of abortion or an abnormal infant is particularly important. In the era of more elaborate and accurate prenatal diagnostic tests, the pathologist examining products of conception has a primary responsibility to detect, in both spontaneous and induced abortions, any developmental abnormality that would indicate an increased risk of multifactorial, chromosomal, and single gene disorders in a subsequent child.

This book is intended as a practical bench manual phological abnormalities in renal diseases, and for the hospital pathologist who wishes to have where appropriate these have been illustrated. access to a simple informative account of renal Although the main emphasis is on the pathology, pathology, particularly for the interpretation of the relevant clinical aspects of the conditions cov percutaneous needle biopsy specimens. I n addition ered are included in recognition of the fact that we trust it will be valuable to physicians working renal disease is an area in which correlation of the in the field of renal disease, for whom the interpre clinical and histopathological findings is particularly tation of renal biopsy material is directly relevant to important in reaching an informed diagnosis. patient management. Whilst a comprehensive coverage more appro priate to a larger text has not been attempted, the Acknowledgements text has been planned to give an adequate account of the more important non-neoplastic disease pro We would like to thank the technical staff of the cesses and their pathological appearances in the Histopathology Laboratories of The London Hos kidney. Points of difficulty in interpretation and dif pital Medical College, The Hospital for Sick Chil ferential diagnosis are covered both in the text and in dren, Great Ormond Street, and Guy's Hospital the illustrations.

Reproduction is, it would appear, a very simple biological event: the result of an act of love. In actual fact, it has always been, and still continues to be, one of the most complex, yet at the same time, most fascinating, problems, with which Science has ever been engaged. Physiopathology of human reproduction has always made use of investigations of a morphological nature, perhaps on account of the need to "see inside" the reproductive apparatus or within the gonads themselves in order to better understand how they function. Observation of spermatozoa practically coincided with the discovery of the microscope, and histological study of the testis and ovary was, for a very long time, the only means available with which to closely follow the evolution of gametes destined to their meeting. Improvement of techniques resulting from the evolution of endocrinology of reproduction has only apparently put aside morphological techniques, whilst at the same time there has been a gradual development of ultrastructural techniques, on the one hand, and, on the other, macroscopic diagnostic systems through images.

The seventh annual multidisciplinary symposium on clinical oncology organised by the Royal College of Radiologists discussed the subject of malignant brain tumours. It was held in London in February 1985 and this volume collects together the edited texts of the papers which were presented at the meeting. Primary tumours of the central nervous system account for about 9070 of all malignant diseases but as much as 20% of all paediatric neoplasms. The prognosis ranges from excellent for some of the less aggressive tumours, through good for children's tumours such as medulloblastoma, to appalling for the high-grade adult astrocytomas. Improvements in pathological diagnosis and surgical and radiothera peutic techniques have led to considerable sequential improvements in outcome over those obtained in the past. In contrast the response to chemotherapy over the whole range of tumours remains disappoint ing, and clearly awaits new drugs and methods of delivery. The relative rarity of individual types of tumours, apart from the commoner high-grade adult astrocytomas, has made progress in terms of clinical trials difficult to organise. In spite of this much investigative work is in progress. The symposium, and the present volume, were designed to provide a comprehensive overview of the subject by experts, with an emphasis on the possible routes to future progress. The topics included aspects of pathology, imaging, diagno sis and treatment of both the common and uncommon primary tumours. It is hoped the papers will stimulate further interest and activity in this difficult area of clinical therapy and investigation."

1h The 5 International Conference on the Progress in Alzheimer's Disease and Parkinson's 51 1 Disease took place from March 31 to April 5 \ 2001 in Kroto, Japan. This international 1 conference was organized as a joint Congress with the 9 International Catecholamine Symposium. A total of 1258 clinicians and researchers participated in this joint congress 1h from 38 countries in the world. This book represents the proceedings of the 5 Conference on Alzheimer's and Parkinson's disease. The International Conference on the Progress in Alzheimer's and Parkinson's disease was first launched by Professor Abraham Fisher of Israel and Professor Israel Hanin of USA. The first conference was held in Eilat, Israel in 1985. The second conference was organized in Kyoto, Japan in 1989; the third one in Chicago, USA, in 1993, and the fourth one in Eilat, Israel in 1997. The International Catecholamine Symposium (ICS) is an international meeting devoted to the development of basic as well as clinical research on catecholamines. The first Catecholamine Symposium was held in Bethesda, USA in 1958. Since then this symposium has occurred every 5 years. Professor Toshiharu Nagatsu was appointed as 1h the president of the 9 International Catecholamine Symposium, which was to be held in 200 I also in Japan. Therefore, we decided to organize a joint congress of the two meetings, because there is much overlap in research between Alzheimer's disease, Parkinson's disease, and catecholamines. We thank Professor Nagatsu very much for agreeing to organizing this joint congress.

The present volume contains the scientific contributions to the Fifth International Symposium on "Current Trends in Sphingo lipidoses and Allied Disorders" under the auspices of the Isaac Albert Research Institute of the Kingsbrook Jewish Medical Center, the Department of Pathology, Downstate Medical Center, State Uni versity of New York, Brooklyn, New York, and the National Tay-Sachs and Allied Diseases Association, Inc., New York. A review of the four previous Symposia shows the increase in scope of the scientific exploration in this rapidly expanding field. The first meeting, held in 1958, was devoted to the discussion al most entirely of Tay-Sachs disease. The majority of the work emanated from local laboratories. The participants at the present Symposium came from many other domestic and foreign research in stitutions. The scope of the papers presented at these meetings and the interest shown in the Symposium demonstrates the signifi cance attached by the scientific community to the problems of these hereditary diseases. The reasons for this are apparent, when one considers the contributions during recent years to our basic know ledge by lipid and enzyme chemistry, genetics, and neuropathology. Partly because of the hereditary nature of these diseases any new discovery in this field has general meaning and permits cautious generalization well beyond its clinical significance."

Melanocytic neoplasms are of capital importance for all surgical pathologists and dermatopathologists. These tumors span a huge range of morphologic expression and biologic behavior, are potentially of the highest medical significance and are often fraught with diagnostic pitfalls and high litigation risk.

"Pathology of Challenging Melanocytic Neoplasms "offers a dynamic text where readers will encounter a broad spectrum of challenging melanocytic lesions, both benign and malignant and will thereby acquire a solid, working knowledge that they can immediately apply to daily diagnosis. The authors aim to clarify this often thorny field, keeping a steady focus on patient-related issues. The volume emphasizes the practical application of basic morphologic principles, immunohistochemistry and molecular methods in order to secure a confident diagnosis. Abundant illustrations display the characteristic features of the most important disease entities.

Rather than being yet another encyclopedic work of reference, this volume takes a fresh approach as it resembles a series of stimulating seminars employing exemplary case material to highlight, illustrate, and succinctly discuss the key points. To this end, the reader will be guided through a series of paired cases that pose a significant diagnostic challenge. By comprehensively comparing and contrasting two related entities, each such chapter will illuminate an intellectual pathway through which an important diagnostic puzzle can be solved. To broaden the differential diagnosis even further, additional illustrative cases are added to each discussion. Algorithms and tables summarize key points. Clinically relevant, up-to-date references will be provided to guide further study. Written by experts in the field, this novel text will be of great value to surgical pathologists in practice and dermatologists as well as residents and fellows training in these specialties.

In a condition of such complexity as bronchial carcinoma and at a time when the scientist's understanding of malignant disease is still incomplete, it is inevitable that views within the medical profession will proliferate. This book is an attempt to assemble these views in the light of 33 years of surgical experience and is intended for those specialists who will be concerned with the diagnosis and treatment of lung cancer in the foreseeable future. The wide clinical experience of the contributing authors has ena bled every aspect of this disease to be considered, with emphasis being placed on diagnostic techniques such as CT scanning and fine needle transpleural biopsy, as well as on the latest method of treatment by lasers. Bronchial carcinoma remains the major cause of cancer death in the United Kingdom, accounting for 60Jo of all deaths. While the incidence has decreased slightly in the male population, there has been an equivalent increase in the female population.

Biotargets of Cancer in Current Clinical Practice presents an updated and reasoned review of the current status of knowledge concerning the major cancer types with a special focus on the current biomarkers, genes involved and the potential future targets of innovative therapies. The volume includes for each major cancer type, a comprehensive although concise discussion of epidemiology, affirmed and innovative biomarkers for diagnosis, and descriptions of the relevant genes for prognosis and (individualized) therapy through biotarget-specific new molecular treatments, with the latest information on the validation status of each novel biomarker. Individual chapters are dedicated to the major cancer types, plus a special chapter on metastasis. The present debate on patentability of genetic information applied to diagnostics and therapeutics of cancer is also discussed.

This atlas is a practical approach to problems commonly encountered in paediatric tumour diagnosis. It comprehensively covers a wide range of common and unusual entities. Over 300 full-colour illustrations are complemented by a text which is pragmatic and succinct. References have been carefully selected to reflect current thought and well-written reviews. New treatment strategies have led to considerable improvement in the salvage rate and prognosis in childhood neoplasia. Histological diagnosis in this area is fraught with problems and the demand invariably has been for a prompt and accurate histological reporting. The problems although wide-ranging, are particularly manifest in the area of the small round-cell tumours which constitute an important proportion of paediatric cancers. This atlas will be invaluable as a bench manual for the practising pathologist and as a study aid for the trainee. It will also be of interest to all oncologists and paediatricians.

Autoimmune myasthenia gravis (MG) is a classical autoimmune disease, for which the target antigen, nicotinic acetylcholine receptor, has been cloned, sequenced and biochemically characterized. Antibodies to acetylcholine receptors destroy acetylcholine receptor at the neuromuscular junction, thus leading to defective neuromuscular transmission, muscle fatigue, and weakness. In the last few years, rapid advances have been made in unraveling the cellular and molecular mechanisms involved in the pathogenesis of MG, both in the animal model, experimental autoimmune MG (EAMG), and in human MG. Significant advances are being made in characterizing the cells and molecules involved in the autoimmune response to the acetylcholine receptor (AChR). These advances are leading to the development of specific methods of immunointervention in EAMG. Further understanding of the intricate involvement of the major histocompatibility complex (MHC) and non-MHC genes, T cell receptors (TCR), costimulator molecules, and specific cytokines in the afferent and efferent autoimmune response of AChR should pave the way to future antigen/clone-specific therapy of MG. This book is the outcome of the MG workshop proceedings in Mysore, India, 1998. The majority of the chapters in this book are contributed by world-renowned authors and their students. The book not only contains a timely review of specific topics, but also up-to-date findings. Immunologists and neurologists will find, in this volume, the latest in MG/EAMG cutting-edge research. Clinicians will be interested in the applications of the various immunointervention strategies into clinical trials in MG patients. Finally, students will not only be interested in reading the latest in EAMG/MG research, but will also find information to help them develop a future strategy to unravel the precise mechanism of disease. To summarize, in this book, the readers should find up-to-date information related to immunological mechanisms involved in MG pathogenesis and various modalities for possible approaches to immunointervention to treat MG.

The vasculature of the central nervous system (eNS) is characterized by the existence of the blood-brain barrier (BBB), which can be regarded as both an anatomical and physiological phenomenon. The BBB is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages and a basal membrane, although the anatomic substrate of the BBB is the interendothelial tight junctions that form a continuous sealing. The BBB serves as an exquisitely controlled, functional gate to the eNS. It not only protects the brain from agents in the blood that could impair neurological function, but also controls the influx and efflux of numerous substances to maintain proper homeostasis and provide the brain with necessary nutrients. The structural and functional integrity of the BBB was shown to be dramatically altered during various diseases of the eNS, including neoplasia, ischemia, trauma, hypertension, inflammation and epilepsy. Recent years research has partially elucidated the mechanisms underlying the development of some of these brain disorders as well as the pathways used by different pathogens, like bacteria and viruses, to initiate eNS infections. The development of in vitro models of the BBB had instrumental role in the understanding of the involvement of the BBB in the pathogenesis of several eNS diseases. The intimate, functional association between the function of the brain and the activity of the BBB makes the later a target for pharmacological modulation that will expand the therapeutic possibilities for a range of neurological diseases.

Toxicological and pharmacological effects arise when chemicals interact with biophysiological functions in discrete cell types. There is a continuing need to screen novel compounds for their potential therapeutic effects, and once these have been "discovered" to understand their molecular actions, as the basis of using such compounds safely and for rational drug design. Pharmacology now uses all of the sophisticated molecular research techniques that are available for the development of safer and more efficacious drugs. Histochemistry has been usefully applied to developing new drugs (and assessing chemical safley) and is potentially cost effective. The need to test novel substances for their potential adverse effects has raised many questions. Toxicological pathology has moved away from the cataloging of lesions towards understanding the basis of the events that underly cell injury, especially for those secondary consequences of chemical injury that lead to malignancy and chronic disease. The focal nature of toxicologic lesions de mands the use of microtechniques to provide data to help understand these questions. Histochemistry is under-utilized, but offers one of the key ap proaches necessary to address the problem of understanding interactions between a cell population and a chemical, the modulation of cellular biochem istryor the presence of a lesion in a test animal can be rationalised in terms of species differences that have no relevance to man as opposed to those that are of clinical significance or represent a warning of dire consequences to man.

Like all specialized areas of medicine, that of joint disease informative. The techniques, practical and interpretive, has become surrounded by a practical mystique and are highly reproducible and simple, allowing them to be applied in any laboratory. jargon specific to itself. The number of clinicians working Although we see this volume as being of value to all in the field is large but the number of pathologists small. interested in joint disease it is specifically aimed at It follows that the majority of pathologists are at somewhat laboratory staff wishing to offer a synovial fluid analytical of an immediate disadvantage when discussing and ana service. Like most cytology we believe much of the cell lysing articular problems with their rheumatological and and non-cell identification and quantitation can, and orthopaedic colleagues. should, be undertaken by trained technical staff. The book In the specific area of synovial fluid examination the is therefore aimed primarily at two groups: pathologists difficulties for the pathologist are compounded because who do not specialize in joint disease and technical staff to date there have been no basic texts that detail the who will be generating the data on which interpretation methods, findings and interpretation of the macroscopic will be based. It is therefore both a text book and a bench and microscopic characteristics of the fluid in the common reference manual. arthropathies. In this book we hope to go some way We do not believe our data or methodology represent towards rectifying this omission."

This volume contains selected works from the 25th Anniversary of the International Conference on Intracranial Pressure (ICP) held in Williamsburg, Virginia. The theme of the meeting was Intracranial Pressure and Neuromonitoring and focused on all the current state of the art brain monitoring methodologies and their application to brain injury. The brain monitoring techniques covered a wide spectrum from neurochemical monitoring of the injured brain to specialized techniques for assessing shunt function in normal pressure hydrocephalus. It also includes the most recent advances in monitoring of the brain oxygen levels using electrodes or the less invasive Near Infrared Sprectroscopy devices. Controversial issues regarding the management of ICP and CPP or both are also addressed and there are several works dealing with this topic. Of particular interest is the group of papers describing diagnosis and outcome in normal pressure hydrocephalus. It is the first compilation of papers which covers all the latest brain monitoring studies in both ischemia, trauma and hydrocephalus. The manuscripts in this volume have been selected from over 300 abstracts submitted to this international symposium. The abstracts are also published in order to provide the most comprehensive view of the progress made in brain injury research.

Alzheimer disease (AD) has become the most common form of dementia in industrialized countries and represents an increasing burden at the economic, social and medical level. In discussing both the biological aspects of AD as well as the cognitive functions involved, Alzheimer Disease - Neuropsychology and Pharmacology presents a comprehensive picture of the pathology and approaches to diagnosis and treatment. Basic research including animal models, molecular and genetic aspects is also taken into consideration. In part I, the biological correlates of AD are discussed. In part II the neuropsychological aspects such as cognitive impairment, loss of functional autonomy and emergence of neuropsychiatric disturbances of AD are outlined. In part III, strategies for effective treatment and prevention of AD are discussed. This book will be a useful source of information for clinicians as well as researchers in the area of neuropharmacology.

Aging represents a physiological and "per se" non-pathological and multifactorial process involving a set of key genes and mechanisms being triggered by different endogenous and exogenous factors. Since aging is a major risk factor in connection with a variety of human disorders, it is increasingly becoming a central topic in biochemical and medical research. The plethora of theories on aging some of which have been discussed for decades are neither isolated nor contradictory but instead can be connected in a network of pathways and processes at the cellular and molecular levels. This book summarizes the most prominent and important approaches, focusing on telomeres, DNA damage and oxidative stress as well as on the possible role of nutrition, the interplay between genes and environment (epigenetics) and intracellular protein homeostasis and introduces some genes that have actually extended life spans in animal models. Linking these different determinants of aging with disease, this volume aims to reveal their multiple interdependencies. We see that there is no single perfect theory of aging and that instead it is possible to define what the authors call the "molecular aging matrix" of the cell. A better knowledge of its key mechanisms and the mutual connections between its components will lead to a better understanding of age-associated disorders such as Alzheimer s disease."

This book 1. explores current methods and techniques employed by paleopathologists as means to highlight the range of data that can be generated. 2. introduces a range of diseases and conditions that have been noted in the fossil, archaeological, and historical record, offering readers a foundational understanding of pathological conditions, along with their potential etiologies. 3. will be indispensable for archaeologists, bioarchaeologists and historians, and those in medical fields, as it reflects current scholarship within paleopathology and the field's impact on our understanding of health and disease in the past, the present, and implications for our future.

In the front material of this book both a foreword and a preface appear. What the content of a preface should be is well understood. It is the author's retrospective account of intent, of the labors to accomplish that intent, and of the content of the book that resulted. What a foreword should be is less obvious. Most properly, it is perhaps the brief testimony of one who knows the accomplishments of the author and the scope of the field and who may direct readers to the book. On some basis, the writer is assumed to have earned the right to undertake such a task. To undertake the writing of a foreword for so considerable a researcher, teacher, and scholar as Alfred Evans can be seen not only as an honor but also as a daunting one. My first thought, in truth, is that this wine needs no blush and that no foreword is needed. As John Rodman Paul Professor of Epidemiology at Yale, Alfred Evans has an established reputation in the field of causality. We have learned from his insights about the evolution of causal thinking as epidemiology passed from the era of the germ theory into that of the search for causes of chronic noncontagious diseases. It was he who drew attention to the effect of specific context in that evolution.

These proceedings of the 5th Prouts Neck Meeting on Prostate Cancer, held in October, 1989, highlight the many advances in the understanding of prostatic growth and function at the cellular and molecular levels which have been registered since the first Prouts Neck Meeting in 1985, a meeting which also focused on the then current concepts and basic approaches to understanding prostate cancer. Inter vening Prouts Neck Meetings in 1986, 1987 and 1988 were devoted to treatment, image cytometry and clinical markers. As before, the Prouts Neck tradition of bringing together an international, multidiscipli nary group of experts for 3 days to exchange ideas and new data, in the relaxed atmosphere of an old iun on the scenic Maine coast, proved to be an ideal combination for a highly successful conference. Accordingly, the Organ System Program of the National Cancer Institute plans to use the Prouts Neck model for future conferences on other solid tumors (bladder in 1990 and kidney in 1991) and will return to the prostate in 1992. A new dimension was added to the current program through the inclusion of a poster session to recognize the research of pre-and postdoctoral investigators. The posters were judged by Drs. Collette Freeman, Frank French, Shutsung Liao, Robert Matusik and Henry Sun. The three winners, in alphabeti cal order, were John Fabian, Robert Getzenberg and Ming Fong-Lin."

nd During June 13 -June 23 1996, the 2 EL. B. A. Foundation course on Genome, a NATO Advanced Study Institute, was held at Marcian Marina, Isle of Elba, Italy, - sponsored by the North Atlantic Treaty Organization and the EL. B. A. Fundation. The subject of the course was "Genome Structure and Function" with participants selected worldwire from 15 afferent countries. The purpose of the course and of the resulting book is the study of DNA structure (from the primary to the quintemary) and gene expression in the control of cell function and cell cycle progression; the topics were presented by top experts, covering both structural (cbwn to the atomic resolution) and functional (cbwn to gene level) aspects. The topics were presented by top experts and scientists active in the field, with the goal to give an insight into modm problems of genome study and recent ochievements in related fielm of molecular and cell biology, genetic engineering, biochemistry and biophysics, oncology and biotechnology. This resulting book is intenred to give a broad perspecti ve of the current stand of these fields. The major emphasis is towarm a reep unrerstanang of DNA structure and function in intetphase and metaphase chromosomes, originating by the parallel biophysical (namely NMR X-Ray and neutron scattering, spectropolarimetry, image analysis, calorimetry) and biochemical study conwcted on a wire range of cell systems placing the emphasis on either the higher orrer DNA structure or gene structure and function.

Metastases determine malignancy. The main attention so far has been focused upon organ metastases. The molecular mechanisms thereof, while far from being totally elucidated, are increasingly well understood. Modern diagnostic tools now enable detection and precise localization of small lesions. In contrast, our knowl edge and diagnostic capabilities regarding metastatic spread to the'lymphatic system are rather limited. However, there have re cently been a number of interesting advances. It is the aim of this volume to submit these developments to detailed analysis. The therapeutic relevance of enhanced sensitivity in detection of lymph node metastases has to be considered in the light of in creased morbidity versus eventual prognostic improvements by modification of therapy. An interesting concept which might im prove diagnostic accuracy while reducing operative morbidity is the "sentinel node" technique. Surgical standards are lacking, however, and many fundamental questions pertaining to precise lymphatic mapping remain unanswered. Whether the sentinel node concept is of general relevance or whether it is applicable in only a few organs remains to be determined. This book offers intensive discussion of the concept from methodological and tu mor biological viewpoints. World-renowned experts with long term involvement in related basic and clinical research provide the reader with a broad survey of actual knowledge together with a critical appraisal of recent and future developments. We sincerely hope this book succeeds in providing an outlook as a reference for all clinicians on future prospects and serving and researchers in this extremely important field.

Larry L. Hench June Wilson OBJECTIVE Millions of people presently enjoy an improved quality of life due to prostheses which repair, augment or replace parts of their skeletal system: bones, joints, teeth, etc. However, all replacement parts have a finite probability of survival. The goal of this book is to compare the survivability data for various skeletal prosthesis systems. All data derive from previously published clinical studies. Where possible statistical comparisons are made and the reasons for failure are discussed. THE NEED FOR SKELETAL PROSTHESES We are an aging population with more than 100 million people in the U. S. and Europe over the age of 50 years. An unfortunate consequence of aging is a progressive deterioration of the quality of skeletal tissues. From the age of 30 years there is a decrease in bone mass for both men and women (Fig. 1. 1). However, for women it is much greater and between 40 and 60 years of age the rate of deterioration of long bones and vertebrae of women is especially severe due to hormonal changes. By the age of 70 most women will have lost from 35 to 60% of their bone mass. The loss of volume of cancellous or trabecular bone leads to a large decrease in mechanical compressive strength (Fig. 1. 2). The clinical consequence is an increasing incidence of vertebral collapse. Cortical bone decreases in tensile strength with age (Fig. 1.