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DOI: 10.1055/s-0038-1632727
On age-related mammalian bone loss: Insights of the Utah paradigm
Publication History
Publication Date:
08 February 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035023/200203/lookinside/thumbnails/10-1055-s-0038-1632727-1.jpg)
Summary
An elegant design stratagem would make its loads control the strength of an organ intended to carry loads without breaking. Healthy load-bearing mammalian bones do exactly that. Physiologists begin to understand how they do it, and this article reviews some of the biological “machinery” responsible for it. Why? Because that machinery’s features show what can cause age-related bone loss, how it occurs, how a long-overlooked mechanism in bone marrow would contribute to it, why loss of whole-bone strength seems more important than loss of bone ‘mass’, and why some absorptiometric indicators of whole-bone strength are unreliable. The machinery’s features also show why strong muscles normally make strong bones, why persistently weak muscles normally make weak bones, and why loss of muscle strength usually causes a disuse-pattern osteopaenia.
Those things could question long-accepted ‘wisdom’, but four observations concern that; (1) the questions concern what facts mean far more than the accuracy of the facts, and the basic facts now seem pretty clear;
(2) this article must leave resolution of such questions, and of the devils that can hide in the details, to other times, places and people;
(3) the plate tectonics story showed that better facts and ideas can change accepted wisdom dramatically;
(4) and poor interdisciplinary communication delayed and still delays diffusion of better facts and ideas to many skeletal science and clinical disciplines that needed and need them.
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References
- 1 Banu MJ, Orhii PB, Mejia W, McCarter RJM, Mosekilde L, Thomsen JS, Kalu DN. Analysis of the effects of growth hormone, voluntary exercise, and food restriction on diaphyseal bone in female F344 rats. Bone 1999; 25: 479-80.
- 2 Burr DB, Martin RB. Mechanisms of bone adaptation to the mechanical environment. Triangle (Sandoz) 1992; 31: 59-76.
- 3 Burr DB. Muscle strength, bone mass, and age-related bone loss. J Bone Miner Res 1997; 12: 1547-51.
- 4 Carter DR. Mechanical loading histories and cortical bone remodeling. Calc Tiss Int Suppl 1984; 36: 19-24.
- 5 Currey JD. The Mechanical Adaptations of Bones. Princeton University Press; Princeton: 1984
- 6 Favus MJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral. Metabolism. (Ed) (4th ed).. Lippincott-Williams and Wilkins; Philadelphia, PA: 1999
- 7 Ferretti JL, Spiaggi EP, Capozza R, Cointry G, Zanchetta JR. Interrelationships between geometric and mechanical properties of long bones from three rodent species with very different biomass: phylogenetic implications. J Bone Min Res 1992; (Suppl. 02) 423-5.
- 8 Ferretti JL, Capozza RP, Cointry GR, Garcia SL, Plotkin H, Avlarez MLFigueira, Zanchetta JR. Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 1998; 22: 683-90.
- 9 Ferretti JL, Frost HM, Schiessl H. On new opportunities for absorptiometry. J Clin Densitom 1998; 01: 41-53.
- 10 Ferretti JL. Peripheral, quantitative computed tomography (pQCT) for evaluating structural and mechanical properties of small bones. In: Practical Guide for Mechanical Testing of Bone. An YH, Draughn RA. eds. CRC. Press; Boca Raton, FL: 1999: 1-25.
- 11 Frost HM. Mathematical Elements of Lamellar Bone Remodelling. Charles C Thomas; Springfield: 1964
- 12 Frost H. Laws of Bone Structure. Charles C Thomas; Springfield: 1964
- 13 Frost HM. Bone Dynamics in Osteoporosis and Osteomalacia. Charles C Thomas; Springfield: 1966
- 14 Frost HM. Tetracycline-based histological analysis of bone remodeling. Calc Tiss Res 1969; 03: 211-37.
- 15 Frost HM. A method of analysis of trabecular bone dynamics. In: Bone Histomorphometry/1976. Meunier PJ. ed. Armour-Montagu; Paris: 1977: 445-75.
- 16 Frost HM. Secondary osteon population densities: An algorithm for estimating the missing osteons. Yearbook of Physical Anthropology 1987; 30: 239-54.
- 17 Frost HM. Perspectives: A proposed general model of the mechanostat (suggestions from a new paradigm). Anat Rec 1996; 244: 139-47.
- 18 Frost H. Osteoporoses: New Concepts and Some Implications for Future Diagnosis, Treatment and Research (based on insights from the Utah paradigm). Ernst Schering Research; Foundation AG: 1998: 7-57.
- 19 Frost HM. On rho, a marrow mediator and oestrogen: Their roles in bone strength and “mass” in human females, osteopaenias and osteoporoses (insights from a new paradigm). J Bone Miner Metab 1998; 16: 113-23.
- 20 Frost HM. A New Approach to Estimating Bone and Joint Loads and Muscle Strength in Living Subjects and Skeletal Remains. Am J Human Biol 1999; 11: 437-56.
- 21 Frost HM. The Utah paradigm of skeletal physiology: An overview of its insights for bone, cartilage and collagenous tissue organs. J Bone Miner Metab 2000; 18: 305-16.
- 22 The author’s personal observation(s) during 50+ years as an orthopaedic surgeon, teacher, researcher and amateur pathologist, and of a matter others must have observed too so it need not be original to the author. However it did not previously seem important or relevant enough to deserve formal study and publication..
- 23 Garn S. The Earlier Gain and Later Loss of Cortical Bone. Charles C Thomas; Springfield: 1970
- 24 Gasser JA. Modulation of strain sensing: A new approach for the treatment of osteoporosis. In: Musculoskeletal Interactions. Vol II. Lyritis GP. ed. Hylonome Editions; Athens: 1999: 77-82.
- 25 Hamrick MW, McPherron AC, Lovejoy CO, Hudson J. Femoral morphology and cross-sectional geometry of adult myostatin-deficient mice. Bone 2000; 27: 343-9.
- 26 Jaworski ZFG. Lamellar bone turnover system and its effector organ. Calc Tiss Int 1984; (Suppl. 36) 46-55.
- 27 Jee WSS. The skeletal tissues. In: Cell and Tissue Biology. A Textbook of Histology. Weiss vL. ed. Urban and Schwartzenberg; Baltimore: 1989: 211-59.
- 28 Jee WSS. Proceedings of the International Conference on Animal Models in the Prevention and Treatment of Osteopaenia. Bone 1995; 17 (Suppl): 1-466.
- 29 Jee WSS. The interactions of muscles and skeletal tissue. In: Musculoskeletal Interactions. Vol II. Lyritis GP. ed. Hylonome Editions; Athens: 1999: 35-46.
- 30 Jee WSS. Hard Tissue Workshops organized annually since 1965 by Prof Jee provided a multidisciplinary forum for presenting and discussing new methods, evidence and ideas about human skeletal disorders. Attended by hundreds of international authorities and fellows in many disciplines, the University of Utah sponsored them and private and federal funds supported them. They probably had more effect on how people think about and study skeletal disorders than any other meetings in this century. The Utah paradigm had its genesis at these Workshops; hence its name..
- 31 Jiang Y, Zhao J, Rosen C, Gensens P, Genant H. Perspectives on bone mechanical properties and adaptive response to mechanical loading. J Clin Densitom 1999; 02: 422-33.
- 32 Keshawarz NM, Recker R. Expansion of the marrow cavity at the expense of cortex in postmenopausal osteoporosis. Metab Bone Dis Rel Res 1984; 05: 223-8.
- 33 Kiratli BJ. Immobilization osteopaenia. In: Osteoporosis. Marcus R, Feldman D, Kelsey J. eds. Academic Press; Orlando, FI: 1996: 833-50.
- 34 Koch JC. The laws of bone architecture. Am J Anat 1917; 21: 177-298.
- 35 Lewis FT. Stohr’s Histology. ed. 6th U.S. ed. P Blakiston’s Son and Co; Philadelphia: 1906
- 36 Marotti G. The structure of bone tissues and the cellular control of their deposition. Ital J Anat Embryol 1996; 101: 25-79.
- 37 Martin RB, Burr DB, Sharkey NA. Skeletal Tissue Mechanics. Springer-Verlag; New York: 1998
- 38 Martin RB. Towards a unifying theory of bone remodeling. Bone 2000; 26: 1-6.
- 39 McLean FC, Urist MR. Bone (2nd ed). University of Chicago Press; Chicago: 1961
- 40 Parfitt AM. Osteoporosis: 50 years of change, mostly in the right direction. In: Osteoporosis and Bone Biology. Compston J, Ralston S. eds. International Medical Press; 2000: 1-13.
- 41 Parks NJ, Jee WSS, Dell RB, Miller GE. Assessment of cortical and trabecular bone distribution in the Beagle skeleton by neutron activation analysis. Anat Rec 1986; 215: 230-50.
- 42 Pienkowski D, Pollack SR. The origin of stress generated potentials in fluid saturated bone. JOrthop Res 1983; 01: 30-41.
- 43 Recker RR. Bone Histomorphometry. Techniques and Interpretation). CRC Press; Boca Raton: 1983
- 44 Riggs BL, Melton III LJ. Osteoporosis. Etiology, Diagnosis and Treatment (2nd ed). Lippincott-Raven Publishers; Hagerstown, MD: 1995
- 45 Schiessl H, Frost HM, Jee WSS. Perspectives: Oestrogen and bone-muscle strength and “mass” relationships. Bone 1998; 22: 1-6.
- 46 Schiessl H, Willnecker J. Muscle cross sectional area and bone cross sectional area in the lower leg measured with peripheral computed tomography. In: Musculoskeletal Interactions. Vol II. Lyritis GP. ed. Hylonome Editions; Athens: 1999: 47-52.
- 47 Schönau E, Westermann F, Mokow E, Scheidhauer K, Werhahn E, Stabrey A, Miiller-Berghaus J. The functional muscle-bone-unit in health and disease. In: Paediatric Osteology. Prevention of Osteoporosis - a Paediatric Task?. Schönau E, Matkovic V. eds. Excerpta Medica; Amsterdam: 1998: 191-202.
- 48 Sedlin ED, Frost HM, Villanueva AR. Variations in cross-section area of rib cortex with age. J Gerontol 1963; 18: 9-13.
- 49 Sedlin Uses of bone as a model system in the study of aging. In: Bone Biodynamics. Frost HM. ed. Little-Brown Co; Boston: 1964: 655-66.
- 50 Seeman E. From density to structure: Growing up and growing old on the surfaces of bone. J Bone Miner Res 1997; 12: 509-21.
- 51 Smith RR, Walker RR. Femoral expansion in aging women: Implications for osteoporoses and fractures. Science 1964; 145: 156-7.
- 52 Smith EL, Gilligan C. Mechanical forces and bone. Bone Min Res 1989; 06: 139-73.
- 53 Takahashi H, Frost HM. Age and sex related changes in the amount of cortex of normal human ribs. Acta Orthop Scand 1966; 37: 122-30.
- 54 Takahashi HE. Spinal Disorders in Growth and Aging. ed. Springer-Verlag; Tokyo: 1995
- 55 Turner RT, Riggs BL, Spelsberg TC. Skeletal effects of oestrogen. Endocrin Rev 1994; 15: 275-300.
- 56 Weinmann JP, Sicher H. Bone and Bones. 2nd ed. CV Mosby Co; St Louis: 1955
- 57 Wiener N. Cybernetics. MIT Press; Cambridge: 1964
- 58 Wilhelm G, Felsenberg D, Bogusch G, Willnecker J, Thaten I, Gummert P. Biomechanical examinations for validation of the Bone Strength Strain Index SSI, calculated by peripheral quantitative computed tomography. In: Musculoskeletal Interactions. Vol II. Lyritis GP. ed. Holonome Edtions; Athens: 1999: 105-110.
- 59 Wronski TJ, Dann LM, Qi H, Yen C-F. Skeletal effects of withdrawal of oestrogen and diphosphonate treatment in ovariectomzed rats. Calc Tiss Int 1993; 53: 210-6.
- 60 Yao W, Jee WSS, Chen J, Liu H, Ta CS, Cui L, Zhou H, Setterberg RB, Frost HM. Making rats rise to erect bipedal stance for feeding partially prevented orchidectomy-induced bone loss and added bone to intact rats. J Bone Min Res 2000; 15: 1158-68.