Book Review

Clinical and Biochemical Disorders of the Skeleton

N Engl J Med 2006; 354:2518-2519June 8, 2006

Article

Clinical and Biochemical Disorders of the Skeleton
By Roger Smith and Paul Wordsworth. 471 pp., illustrated. New York, Oxford University Press, 2005. $225. ISBN: 0-19-261740-0

Not very long ago, the skeletal system was viewed as a calcium reservoir to which muscles were attached. This view has changed radically with the insights into matrix structural components, enzymes, and factors provided by rare clinical disorders and murine models. Currently, the skeleton is seen as a dynamic organ, with osteoblasts and osteoclasts at the center of the action, communicating with each other by means of secreted factors. Unexpected findings include the common mesenchymal-cell precursor of osteoblasts and adipocytes and the leptin signaling connection between adipose tissue and osteoblasts through the central nervous system. These findings, which continue to emerge at a dizzying pace, add to the excitement of the field and open new venues for research and treatment. How is the medical student or fellow to grasp this rapidly evolving field or the practitioner to apply the new molecular and cellular knowledge? This book about the disorders of the skeletal system is an excellent guide to this translational research.

Clinical and Biochemical Disorders of the Skeleton is aimed at medical students and fellows, but it also will appeal to geneticists, endocrinologists, and rheumatologists. Although it has two authors, its style and organization are unified. The book also benefits from their lifetime accumulations of experience and scholarship. The style is clear, with a refreshing dose of the authors' opinions; this gives the impression that they are speaking to colleagues about a topic in which they are happily engrossed. Each chapter untangles complex topics and includes a foundation of material to help the reader understand the detailed data presented. There are many helpful tables and a useful appendix of terms. Unfortunately, the general index of the book is far short of comprehensive.

The book begins with an introduction to the biology of bone and the diagnosis of bone disease. The discussion of the biology of bone cells includes clear expositions of cell differentiation and signaling, the receptor activator of nuclear factor-κB ligand system, bone-cell remodeling units, and genetic factors. Insights from clinical situations and mouse models are smoothly interwoven. This book also offers unusually clear guidance regarding diagnosis. The different measurements of bone turnover, hormones, and bone density, the interpretation of these measurements and the extent of their usefulness, and the role of bone biopsy and histomorphometry are all presented in scientific context and with information about limitations and pitfalls.

The second section of the book includes chapters on the classic metabolic disorders of the skeleton, such as osteoporosis, rickets, parathyroid disorders, Paget's disease, and neoplastic disease. The third section, fully half of the book, describes genetic and rare conditions, including disorders caused by structural changes to molecules (collagenopathies and conditions associated with fibrillin defects) and by defects and deficiencies in enzymes (homocystinuria and hypophosphatasia) and factors involved in signal transduction (the McCune–Albright syndrome), growth (bone morphogenetic protein–4 overexpression in fibrodysplasia ossificans progressiva), and differentiation (defective osteoclasts in osteopetrosis). In their discussions of each topic, the authors expound on pathophysiology, clinical features, diagnosis, radiologic findings, and treatment. In the chapter on osteoporosis, for example, they discuss the currently hot topics of cell biology and osteoclast recruitment, bone microarchitecture, genetic modifiers, bisphosphonate therapy, the practicalities of various types of vertebral fractures, and the diagnosis and prevention of bone loss. Heavier books on rheumatology, genetics, connective tissue, and endocrinology address aspects of this material at greater length for the specialist, but this more compact book should provide clinicians with the clinical material and supportive science that exist at the intersection of these fields.

Joan C. Marini, M.D., Ph.D.
National Institute of Child Health and Human Development, Bethesda, MD 20892
oidic@helix.nih.gov