Revival of Bone Strength: The Bottom Line

The continual innovation and proliferation of new research tools for the evaluation and characterization of the skeleton has greatly broadened our understanding of bone physiology and pathology. As the introduction of bone densitometry some 40 years ago was claimed to revolutionize skeletal research—through enabling a quick, precise, and easy noninvasive assessment of bone mineral in vivo—it is quite impossible to predict the potential of the most recent methodological advances in imaging techniques and molecular biology. Today, we are not only able to characterize complex microstructural features of even individual trabeculae, but also to evaluate activities of different bone cells within bone. Unfortunately, it seems at times that the methodological surge has occurred at the cost of studies becoming method-driven, instead of being hypothesis-driven— seeking the true biological mechanisms and relationships. Although whole bone strength testing is among the first methods used to evaluate bone mechanical characteristics, it has not become obsolete. (Whole bone strength test pertains to single mechanical testing of whole bones or excised, complete anatomic bone structures [e.g., proximal femur region] until failure and includes threeor four-point bending tests of long bones and compression tests of proximal femur or vertebrae or columns of vertebrae. The main focus of this analysis is solely on the failure load [strength] of the given bone, whereas structural rigidity [stiffness], postyield behavior, and fatigue characteristics are considered secondary in this respect.) Despite the fact that the nonmechanical functions of the skeleton—hematopoiesis and participation in mineral homeostasis—are chiefly attracting the researchers in the field of osteoporosis, we should never forget that the primary function of the skeleton is locomotion of the body and that only adequately rigid and strong bones make this vital function feasible. It is well established that bones somehow perceive loading-induced strains within the structure and gradually adapt the structure through changes in size, shape, or internal architecture to the prevalent loading environment. Whereas the precise spatial location of each bone element is apparently quite trivial to the above noted subsidiary functions, it can be critical in terms of whole bone strength, “the bottom line.” If we do not know whether the bone as an organ has truly strengthened, we have no certainty of knowing whether the possible changes in any of the intermediate or surrogate measures of bone strength denote only a transient phenomenon–like a “snapshot” of a dynamic movement eventually fading away—or actually a strengthened bone structure as a response to the stimulus of interest. This notion necessitates one to broaden the scope from the mere cellular or tissue-level inspection to the evaluation of bones as structures. The following example from sports shows our concern regarding what we consider the somewhat skewed focus of current experimental skeletal research. We all know that the current technology allows us to measure virtually any imaginable physical characteristic during the course of a long jump (e.g., the length and frequency of the stride of the jumper, athlete’s acceleration or velocity at any given phase during the jump, the height of the jump, or even the oxygen consumption of the muscle activity). However, none of these measures separately or in conjunction tell us the absolute final length of the jump, which is the “bottom line” regarding the athletic performance. Analogous to this, with modern devices, we can readily determine the mineral content, volumetric density, size, shape, and an arsenal of other characteristics of whole bones or even individual bone trabeculae at reasonable precision and accuracy, but at the end, what do we know about the whole bone strength with this information alone? There are infinite ways to construct a bone that has a similar strength but a discernible structure. Needless to say, any change in the rate of bone formation or resorption, irrespective of the underlying cause, ultimately translates into microscopic or macroscopic changes in the bone structure, and possibly, but not necessarily, into the mechanical competence of the whole bone. In the end, it is the whole bone strength that effectively covers virtually all of the individual variability that may be instantaneously, sporadically or permanently present in dynamic/static histomorphometry or in structural particulars (size and shape of the bone, cortical thickness and specific cortical geometry, trabecular architecture, etc.), providing the ultimate assay on bone functional capacity. In 2001, van der Meulen et al. stated persuasively that “the skeletal functional integrity can only be assessed by structural strength tests that measure how well the whole bone can bear load—there is no alternative to testing whole