Revival of Bone Strength: The Bottom Line
Article first published online: 21 FEB 2005
Copyright © 2005 ASBMR
Journal of Bone and Mineral Research
Volume 20, Issue 5, pages 717–720, May 2005
How to Cite
Järvinen, T. L., Sievänen, H., Jokihaara, J. and Einhorn, T. A. (2005), Revival of Bone Strength: The Bottom Line. J Bone Miner Res, 20: 717–720. doi: 10.1359/JBMR.050211
- Issue published online: 4 DEC 2009
- Article first published online: 21 FEB 2005
- Manuscript Accepted: 17 FEB 2005
- Manuscript Revised: 14 FEB 2005
- Manuscript Received: 24 MAR 2004
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(1) 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 three- or 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.(2–4) 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.(5) 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.”(6) 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.(2,7)
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.(8) 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 bone strength and conclusions regarding bone mechanical function based solely on geometry or bone mineral content are inappropriate and likely misleading.” To assess the present veracity of this pertinent concern, we reviewed the methodological aspects of all studies published between 1999 and 2003 in Journal of Bone and Mineral Research, Bone, Calcified Tissue International, and Journal of Orthopaedic Research, the leading scientific journals publishing experimental bone research. We considered these journals a representative sample of the prevailing status in the bone field. Altogether, we found 3472 original studies, of which 1109 were designed such that structural mechanical testing could have been applied (i.e., animal or cadaveric studies with whole bones available). However, whole bone strength testing was carried out in only 210 of these (19%), whereas for comparison, the quantification of trabecular bone compartment by bone static histomorphometry was performed in over 39% of the studies (Table 1). Also noteworthy, the message of our survey coincides with Parfitt's(2) concern in his Perspective to JBMR in 1998, where he stated that the characterization of the skeletal responses to various external stimuli had been quite “tissue-level oriented,” focusing on trabecular bone, while considering the bone cortical shell merely as a protective element for the interior cancellous bone compartment rather than a target worthy of examination on its own.
The superiority of cortical bone to trabecular bone in terms of whole bone strength has been pinpointed in several pertinent studies.(9–14) Particularly elegantly, the impact of cortical bone on bone fragility was recently shown in a simulation study where the mechanical consequences of different scenarios of simulated bone atrophy were assessed with microfinite element analysis.(14) After measuring the complete 3D structure of a human radius with μCT, a 20% loss in bone mass was simulated either by reducing cortical thickness, trabecular thickness, trabecular number, or global thinning of both cortical and trabecular structures. The reduction in the estimated whole bone strength was as high as −40% in the reduced cortical thickness model, whereas the corresponding reductions in strength was −10% in both pure trabecular atrophy models and also in the combined, predominantly trabecular loss model, making our case quite obvious. It is, however, recalled that the role of cortical bone may not be so predominant at skeletal sites where the cortical shell is particularly thin (e.g., in vertebral bodies) and the support from the internal trabecular structure is essential.
Although none of the surrogates or determinants of whole bone strength alone are capable of describing the actual mechanical competence of the given bone, a comprehensive assessment of these variables can provide useful insights into (1) adaptive mechanisms the bone employs in coping with loading or other (endocrine, pharmacological, etc.) stimuli and (2) differences observed in the strength of whole bones with a seemingly similar appearance. The complex relationship between whole bone strength and underlying factors has been elaborated by several authors.(5,6,15–19) It is agreed that the strength and rigidity of the whole bone are attributable to interaction of material properties, amount (mass) of material, morphological, organizational, and somewhat confusing quality issues of bone tissue and whole organ. Naturally, the loading condition (magnitude, mode, direction, rate, etc.) largely determines whether the bone breaks or not. In principle, if the magnitude of incident stresses within the bone structure exceeds the capacity of bone material to withstand those stresses, the given structure will fail. Locally, even subtle alterations in the bone structure or material can be crucial in this respect. The complicated interplay between external loading and bone mechanical competence is not addressed further in this Editorial.
Accordingly, we devised a scheme for characterization of the whole bone structure that would facilitate complementing the strength information obtained from biomechanical testing (Fig. 1). Three central aspects of our scheme are bulk, morphology, and texture (quality). For simplicity and because of following reason, we have excluded the material aspect from our approach and primarily focused on relatively coarse structural particulars only. It is, on one hand, appreciated that a sufficiently good material is a necessity for a strong structure, but on the other hand, it may also be that the influence of declined material properties (e.g., known to occur with aging)(20) is eventually seen as alterations in the whole bone structure—through bone adaptation.
The amount of bone tissue volume represents the rudimentary bulk (analogous to a volume of good-quality plaster) of which the whole anatomic bone structure and organ is made, but as such, the bulk is not, and cannot be, fully indicative of the actual bone structure (analogous to the shape and size of the mold filled with the given amount of plaster) or its strength, despite the established, very strong correlation between BMC and structural strength (r > 0.95(20,21)). Indeed, there can be a huge gap between knowing the amount of bone mineral in the given bone and knowing its structural capacity. It is ultimately the whole bone structure, not its mass or mineral content, that substantiates the bone mechanical competence, and sufficiently detailed, independent information on bone structural particulars is thus needed. Axial and cross-sectional dimensions and geometry along the whole bone (morphology) and the 3D tissue organization and composition (texture) within the whole bone can provide such information (Fig. 1). Of note, texture pertains to 3D organization and composition of the bone tissue mainly in a size-independent fashion, whereas most of the geometric and dimensional factors depend on the bone size. Optimally, with access to a set of (numeric) information describing whole bone structure, we should be able to reconstruct a virtual bone that resembles the actual organ in terms of external dimensions and geometry, internal structure, and concomitant strength. This is easier said than done, and thus a simple evaluation of different structural characteristics is probably sufficient. In Table 2, we have outlined such variables and methods (from coarse level to an in-depth analysis) that could be of use in gathering essential information for this particular purpose. Depending on the specific research question, a relatively coarse evaluation of the bone structure (cross-sectional area, mean cortical thickness and density, trabecular density) may be fully sufficient, whereas occasionally a detailed analysis digging down to specific textural features (architectural orientation and anisotropy, cortical porosity, etc.) may be needed. An arsenal of reasonable methodologies is available—the key question is what bone variables would depict the whole bone structure simply but adequately and without redundancy.
“Microcosms cannot predict macrocosms.”(22) This statement refers originally to physics and astronomy and particularly to the axiomatic fact that one cannot predict galaxies or stars solely from knowledge about atoms, although atoms can help explain already-known features of galaxies and stars. Another example a bit closer to everyday life, an anecdote about Niels Bohr, the 1922 Nobelist in physics, conveys the same message: Bohr has said that the knowledge of physical properties of hydrogen and oxygen, the elements of water, does not allow one to predict its “waterish” property.(23) The salient wisdom of these notions was recently linked to bone research by Frost and Jee,(24) who suggested that an attempt to predict the structural (organ-level) functions of the bones from its cell- and molecular-biologic features would be analogous to predicting macrocosms from microcosms. Consequently, the new research methodologies—no matter how sophisticated and fascinating or what detailed information they provide—should not, and do not, relieve us from the duty of measuring the whole bone strength—the bottom line!
This study was supported by grants from the Medical Research Fund of Tampere University Hospital, the Research Council for Physical Education and Sports, Ministry of Education, the Paulon Säätiö Research Foundation, and the AO Research Fund, Switzerland.
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