Many scattered bones do not a skeleton make

The vertebrate skeleton is an amazing organ system. It pleases one by its exquisite architectural and engineering beauty. It impresses by its strength and remarkable adaptability. It is a veritable beehive of cellular activities:it is constantly being remodeled by the concerted action of bone-resorbing and bone-making cells, and its marrow compartment serves as a factory for several lines of blood cells and adult stem cells. It is a storage facility for Ca²⁺ and plays an essential role in maintaining Ca²⁺homeostasis in our bodies. It can fascinate and delight: a trip to any natural history museum with a group of preschoolers or kindergarten children to examine dinosaur skeletons almost never fails to generate excitement. Yet, it can also generate fear as a reminder of our `return to dust', and can elicit deep concerns as we age and its internal structure slowly becomes osteoporotic and more fragile.

The understanding of how this organ system develops, grows and is maintained in the adult has come a long way during the past 25-30 years, as a result of numerous genetic, biochemical, pharmacological, cell biological,biomechanical and clinical studies. This exciting advance is documented in multiple textbooks and review articles, and, of course, in thousands of original research papers. However, for the student, postdoctoral fellow or young scientist who considers entering the field of bone biology, navigating through this mass of published information is a formidable challenge. No single text exists that helps the novice to separate `signals' from `noise' so that the most interesting unsolved problems (the `hot' topics) and the most promising emerging technologies can be identified. It is therefore with considerable interest one opens a book that in around 400 pages promises to represent precisely that type of text, appropriately titled The Skeleton:Biochemical, Genetic, and Molecular Interactions in Development and Homeostasis. Edward J. Massaro and John M. Rogers, the editors of the multi-authored volume, state that their goal was `to provide researchers and students with an overview of selected topics of current interest in bone biology and to stimulate their interest in this fascinating and diverse field'. Have they succeeded? Unfortunately, after spending some time with the book I must sadly report that the editors have not been entirely successful in this endeavor.

The book is divided into six sections, with each section split into several chapters written by different authors. The section titles broadly reflect the sequence of events that characterize the process by which most of the skeleton develops in the vertebrate embryo. In this process, which is known as endochondral bone development (applicable to the formation of all bones,except for parts of the craniofacial skeleton and part of the clavicle),mesenchyme forms condensed regions in which cells differentiate into cartilage-producing chondrocytes. The chondrocytes form cartilage models of the future bones, and these models are then replaced by bone and bone marrow in a process that couples osteoblastic differentiation, angiogenesis and osteoclastic migration with cartilage removal and bone marrow establishment. Reflecting this developmental sequence, the editors have grouped the chapters into sections as follows: Chondrogenesis, Chondrocytes and Cartilage; Control of Skeletal Development; Osteoblastic Cell Differentiation; Bone Induction,Growth and Remodeling; Bone Mineralization; and Skeletal Dysmorphology. These are logical subdivisions of the subject matter, but unfortunately it looks as though the editors stopped their work at this point. It is hard to avoid drawing the conclusion that they did not define a detailed framework for the chapters in each section nor provide the authors with clear guidelines for organizing the chapters. I suspect that they also did not work with the authors on revising their work to achieve a product that would be as close as possible to their planned book. Instead, the editors appear to have decided to write a long preface, almost like a mini-review of bone biology, in a late attempt to provide some sort of cohesive structure to the book. This is not effective. As a result, the book, in my mind, is more like a collection of scattered bones than the kind of treatise on the skeletal organ system I was hoping for when I first opened it.

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Among the many problems that I can only blame on the lack of strong editorial hands, is the unexplained variation in the structure of different chapters. Some are written as concise reviews or a series of mini-reviews(such as chapters 1, 5, 8, 10, 14, 18 and 23) – excellent for students as an introduction to specific topics in extracellular matrix and bone biology. Other chapters (e.g. chapters 4, 12, 19, 22 and 24) are organized in the format of original research papers, with Introduction, Materials and Methods, Results and Discussion. I suspect that most of the data in these chapters have been or will be published in more appropriate peer-reviewed journals in a slightly (or extensively, as the case may be) modified form. In a third category are chapters (such as chapters 6, 11, 13, 15-17 and 20) that provide a mixture of review with a discussion of recent data (with a description of methods and results) from the authors' own laboratories. I suspect that many of these chapters have their origins in the Background and Significance sections of recent grant applications.

The quality of the different chapters is also very variable. This is perhaps to be expected as they are written by different authors, but some editorial intervention would have helped to make the quality more uniform. For example, removing excess and irrelevant material could have helped in Chapter 2 (`Chondrocyte Cell Fate Determination in Response to Bone Morphogenetic Protein Signaling'). This chapter contains, appropriately, a discussion of the bone morphogenetic proteins (BMPs), their receptors and downstream signaling pathways, but it also contains a table, several pages in length, of gene mutations that are responsible for human genetic skeletal disorders and relevant animal models. Such a table is of course useful, but I cannot understand the rationale for incorporating it in this chapter, and not in, for example, a chapter in the section on Skeletal Dysmorphology!

Another example of the lack of editorial intervention is the repetition of the same basic information throughout many chapters. Thus, after reading about BMPs, their receptors and the downstream Smad proteins, in Chapter 2, the reader is treated to another description in Chapter 3. Repeating important facts is based on sound pedagogical principles, but in the case of BMPs this principle is taken to the extreme in this book: a basic description of BMPs and their receptors is repeated in chapters 8, 13, 15 and 16. Editorial intervention would have been very helpful here. It may also have helped to improve Chapter 3, which deals with chondrocyte differentiation. Given what we now know about the essential roles of the transcription factors Sox9, Sox5 and Sox6 in chondrocyte differentiation, it is remarkable that the discussion in this chapter is almost entirely focused on the regulation of chondrocyte activities in the epiphyseal/growth plate regions of developing long bones. A detailed description of the transcriptional machinery required for chondrocyte differentiation is entirely omitted! Finally, one has to ask, `editors, where were you?' when reading the sentence `collagen I consists of a triple-helix formation' finds α1(I) and α2(I) collagen chains are described as Iα1 and Iα2 chains (Chapter 21) in a book that contains an accurate and up-to-date chapter on `Molecular Biology and Biosynthesis of Collagens' (Chapter 5).

By now it should have dawned on the reader that I cannot give this book two thumbs up. This is the bad news. The good news is that although it has too many sharp `bones' to be enjoyed as a full meal, some of the individual`bones' are very good. The chapters written as concise reviews make excellent reading for students and may be useful as reading assignments in introductory courses. Some of the chapters that describe methods and hypotheses will be useful for postdoctoral fellows and researchers in the field who would like to achieve better insights into the experimental strategy and thinking behind the published work from specific laboratories. For example, Chapter 7, which describes the use of the loxP/Cre system in targeted mutagenesis of the mouse Hoxd complex, can be read as a supplement to the Materials and Methods section of recent papers from Duboule's group. Chapter 26, which deals with risk assessment issues, will be useful for corporate scientists working on animal studies as part of their companies' submissions to the US Food and Drug Administration and US Environmental Protection Agency.

The really good news is that the opportunity to write a truly outstanding modern treatise on the vertebrate skeleton is still open. Until that happens,one will have to select and use parts of this book.