Osteoporosis: Genetics, prevention and

treatment
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