From Wolff's law to the Utah paradigm: Insights about bone physiology and its clinical applications

2001 ◽  
Vol 262 (4) ◽  
pp. 398-419 ◽  
Author(s):  
Harold M. Frost
2000 ◽  
Vol 04 (02) ◽  
pp. 67-84 ◽  
Author(s):  
Harold M. Frost

As age, experience and common sense look at biomechanical, hormonal, genetic and other roles in bone physiology and its disorders, two questions can arise: (a) How did we fail? (b) How could we make it better? The acerbic Sam Johnson said that to teach new things, we should use examples of already known ones. If so, an analogy might help to clarify this article's message for people who work with bones and their disorders. Assume this: (a) Mythical physiologists were taught that renal physiology depends on "kidney cells" but were taught nothing about nephrons; (b) so they explained renal health and disorders in those terms. (c) For many decades, they "knew" that view was correct (as the ancients "knew" the world was flat). (d) But then others described nephrons and some errors their properties revealed in those views about renal physiology; (e) so controversies began. Today, an analogous situation confronts real biomechanicians and physiologists. (i) Most of them were taught that osteoblasts and osteoclasts (bone's "effector cells") explain bone physiology without "nephron-equivalent" input, so they explained bone disorders and mechanical effects in those terms. (ii) Yet nephron-equivalent mechanisms and functions, including biomechanical ones, in bones have the same operational relationship to their cells, health and disorders as nephrons and their functions do to renal cells, health and disorders. (iii) Adding that knowledge to former views led to the Utah paradigm of skeletal physiology. It also revealed errors in many former views about bone physiology; (iv) so real controversies have begun. Biomechanicians, physiologists, clinicians and pharmacologists from whom poor interdisciplinary communication hid that paradigm could think the view in (i) above remains valid, and keep analyzing data and designing studies within its constraints. Like Wegner's idea of plate tectonics in geology, the Utah paradigm came before its field was ready, so others fought it. But while the plate-tectonics war was won, it has just begun for the Utah paradigm. This article reviews how such things could apply to bone and some of their implications. Its conclusion offers succinct answers to the italicized questions above.


2002 ◽  
Vol 13 (6) ◽  
pp. 1-6 ◽  
Author(s):  
Setti S. Rengachary

The cellular and molecular events governing bone formation in the embryo, healing of a fractured bone, and induced bone fusion follow a similar pattern. Discovery, purification, and recombinant synthesis of bone morphogenetic proteins (BMPs) constiute a major milestone in the understanding of bone physiology. In this review the author discusses the mechanism of action, clinical applications, dosage, and optimum carriers for BMPs. The roles played by other growth factors are also discussed.


Author(s):  
J.D. Shelburne ◽  
G.M. Roomans

Proper preparative procedures are a prerequisite for the validity of the results of x-ray microanalysis of biological tissue. Clinical applications of x-ray microanalysis are often concerned with diagnostic problems and the results may have profound practical significance for the patient. From this point of view it is especially important that specimen preparation for clinical applications is carried out correctly.Some clinical problems require very little tissue preparation. Hair, nails, and kidney and gallbladder stones may be examined and analyzed after carbon coating. High levels of zinc or copper in hair may be indicative of dermatological or systemic diseases. Nail clippings may be analyzed (as an alternative to the more conventional sweat test) to confirm a diagnosis of cystic fibrosis. X-ray microanalysis in combination with scanning electron microscopy has been shown to be the most reliable method for the identification of the components of kidney or gallbladder stones.A quantitatively very important clinical application of x-ray microanalysis is the identification and quantification of asbestos and other exogenous particles in lung.


Author(s):  
A. LeFurgey ◽  
P. Ingram ◽  
L.J. Mandel

For quantitative determination of subcellular Ca distribution by electron probe x-ray microanalysis, decreasing (and/or eliminating) the K content of the cell maximizes the ability to accurately separate the overlapping K Kß and Ca Kα peaks in the x-ray spectra. For example, rubidium has been effectively substituted for potassium in smooth muscle cells, thus giving an improvement in calcium measurements. Ouabain, a cardiac glycoside widely used in experimental and clinical applications, inhibits Na-K ATPase at the cell membrane and thus alters the cytoplasmic ion (Na,K) content of target cells. In epithelial cells primarily involved in active transport, such as the proximal tubule of the rabbit kidney, ouabain rapidly (t1/2= 2 mins) causes a decrease2 in intracellular K, but does not change intracellular total or free Ca for up to 30 mins. In the present study we have taken advantage of this effect of ouabain to determine the mitochondrial and cytoplasmic Ca content in freeze-dried cryosections of kidney proximal tubule by electron probe x-ray microanalysis.


1976 ◽  
Vol 40 (2) ◽  
pp. 106-106
Author(s):  
DL Torney ◽  
HD Espinosa

1994 ◽  
Vol 3 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Theresa A. Kouri

Lexical comprehension skills were examined in 20 young children (aged 28–45 months) with developmental delays (DD) and 20 children (aged 19–34 months) with normal development (ND). Each was assigned to either a story-like script condition or a simple ostensive labeling condition in which the names of three novel object and action items were presented over two experimental sessions. During the experimental sessions, receptive knowledge of the lexical items was assessed through a series of target and generalization probes. Results indicated that all children, irrespective of group status, acquired more lexical concepts in the ostensive labeling condition than in the story narrative condition. Overall, both groups acquired more object than action words, although subjects with ND comprehended more action words than subjects with DD. More target than generalization items were also comprehended by both groups. It is concluded that young children’s comprehension of new lexical concepts is facilitated more by a context in which simple ostensive labels accompany the presentation of specific objects and actions than one in which objects and actions are surrounded by thematic and event-related information. Various clinical applications focusing on the lexical training of young children with DD are discussed.


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