Book Review

Osteoporosis: Genetics, prevention and treatment

N Engl J Med 2000; 342:1683June 1, 2000

Article

Osteoporosis: Genetics, prevention and treatment
Edited by John S. Adams and Barbara P. Lukert. 308 pp. Boston, Kluwer Academic, 1999. $180. ISBN: 0-7923-8366-4

Osteoporosis causes 1.5 million fractures and costs more than $14 billion annually in the United States alone; with these rates still increasing, it is a worthy subject for discussion. This book is part of a series intended to update endocrinologists about the latest developments in osteoporosis. The combination of three themes — genetics, prevention, and treatment — in a book of this size is a very ambitious project in an area as exciting and fast-moving as osteoporosis research.

The first section, consisting of four chapters, deals with genetics and focuses primarily on skeletal morphogenesis, with a frightening list of proteins and receptors, an excellent overview chapter on animal models, and a scanty chapter on human disease. Although we are told the importance of genetics, that the heritability of bone density may be as high as 85 percent, there is no discussion of epidemiologic studies that show that the risk of fractures is doubled in the daughters of women with fractures, independently of density. There is no definition of concepts such as heritability (also confusingly referred to as heredity and inheritability). Many important questions remain unanswered, including the potential clinical and preventive roles of the two main and controversial candidate genes, the vitamin D receptor gene and the collagen I gene, and how genes can be used therapeutically, depending on their structural and metabolic properties. Should we be looking for genes affecting the risk of fracture rather than its surrogate, bone density? The book also suggests that there are only 5 to 10 osteoporosis genes, although it is likely that there are many more. What about genes involved in bone turnover? How will the Human Genome Mapping Project help researchers and clinicians?

The five chapters on diagnosis, prevention, and treatment are more straightforward and clearer in their aims. However, several controversial areas of topical importance are omitted. A more critical appraisal from a public health perspective would have been helpful and could have included some discussion of the relative costs and benefits of screening with bone density measurements (or ultrasonography), the use of dietary vitamin supplements, and the long-term roles and risks of estrogen-replacement therapy. There are other problems, as well, that should have been addressed: the increased risk of breast cancer in women taking hormone-replacement therapy; the efficacy of estrogens, which may not be as high as we previously thought; and the evidence that estrogens provide no long-term benefit if used for only 5 to 10 years at the time of menopause. It would have been useful to have some discussion of the advantages of treating or preventing osteoporosis much later in life, more up-to-date coverage of the mechanisms of action of drugs such as the bisphosphonates (the mechanisms of which are known to vary), and the observation that only a proportion of the efficacy of osteoporotic drugs in preventing fractures can be explained by changes in bone density.

Six chapters deal with specific osteoporosis syndromes in a more detailed and comprehensive manner, and particularly useful sections include those on renal osteoporosis and on cancer and bone disease. A too-short final chapter usefully summarizes future directions in therapy, concentrating on hormonal modification and underplaying genes and the exciting field of bone-cell manipulation, by which stem cells may be steered toward development into osteoblasts rather than fat cells.

Although it contains a few nuggets of clarity and information, this book overall is a disappointment and does not hang together coherently. The authors have been badly let down by the publishers. The font looks like the bottom line of a 1960s optician's chart; there are typographic errors on nearly every page (some, such as “humorous” for “humerus” are amusing, whereas others such as “a real” rather than “areal” for bone density are misleading); and the mixed-up numbering of the references in many chapters makes the references next to useless. In addition, the figures and tables are poor in quality, printed in a blurred black and white; some require a magnifying glass to be read. The final criticism is that the chapters were written three years ago, and as they say, time waits for no one, particularly in the fields of genetics and osteoporosis. Perhaps the next version of this book can go on the World Wide Web.

Tim D. Spector, M.D.
St. Thomas' Hospital, London SE1 7EH, United Kingdom