Biologically rational ways of bone mass loss prophylaxis and treatment

Cover Page

Cite item


Aim. Based on own and literature date to define biologically rational elements of complex approach to bone mass loss prophylaxis and treatment. Nowadays there are two points of view regarding bone mass loss prophylaxis and treatment. The first favor pharmaceuticals as a basic and physical exercises as additional. According to the second, therapeutic and prophylactic significance of physical exercises in maintenance and development of structural and functional capacities of musculoskeletal system is fundamental. The latter approach correspond to evolutionary formed biological model in that muscles act upon levers - bones that connected by means of joints and provide the movement of the body against gravity. The present work from pathogenethically point of view establish the systemic approach to the bone mass loss prophylaxis and treatment. It is based on physical exercises while additional pharmacotherapy that should aim for optimization of regulatory function of bone cells, first of all osteocytes providing for adaptational reorganisation of bone structures.


About the authors

A. S. Avrunin

Vreden Russian Research Institute of Traumatology and Orthopedics

Author for correspondence.
senior researcher of the scientific department of the diagnosis and treatment of musculoskeletal system diseases and injuries Russian Federation

A. A. Doktorov

All-Russian Research Institute on Medicinal and Aromatic Plant

professor the head of morphology department Russian Federation


  1. Аврунин* А.С., Тихилов Р.М., Шубняков И.И., Плиев Д.Г., Попов В.В., Емельянов В.Г. Минимально необходимое количество исследований ПМПКТ методом ДЭРА при индивидуальной диагностике остеопороза и мониторинге состояния скелета по дистальному отделу предплечья (предварительные рекомендации). Ортопедия, травматология и протезирование. 2009; (1):49-56.
  2. Аврунин А.С., Тихилов Р.М., Шубняков И.И. Медицинские и околомедицинские причины высокого внимания общества к проблеме потери костной массы. Анализ динамики и структуры публикаций по остеопорозу. Гений ортопедии. 2009; (3):5-11.
  3. Аврунин А.С., Тихилов Р.М., Шубняков И.И., Плиев Д.Г., Попов В.В. Проксимальный отдел бедра. Минимально необходимое количество исследований ПМПКТ методом ДЭРА для нивелирования случайной ошибки аппаратно-программного комплекса. Вестник рентгенологии и радиологии. 2010; (1/2):51-57.
  4. Аврунин А.С., Тихилов Р.М., Шубняков И.И., Карагодина М.П., Плиев Д.Г., Товпич И.Д. Ошибка воспроизводимости аппаратно-программного комплекса Lunar Prodigy (version Encore) (Prodigy) при исследовании фантомов и костных структур. Гений ортопедии. 2010; (4):104-110.
  5. Аврунин А.С., Тихилов Р.М., Паршин Л.К., Мельников Б.Е. Остеоциты и пути оптимизации механического гомеостаза скелета с позиций функциональной остеологии. Морфология. 2012; (4):7-13.
  6. Аврунин А.С., Паршин Л.К., Мельников Б.Е. Критический анализ теории механостата. Часть II. Стабильность механометаболической среды скелета и гомеостатических параметров кальция организма. Травматология и ортопедия России. 2013; (1):127-137.
  7. Аврунин А.С., Паршин Л.К., Мишин М.В. Алгоритм минимизации ошибки воспроизводимости метода двухэнергетической рентгеновской абсорбциометрии до клинически незначимых величин. Вестник рентгенологии и радиологии. 2013; (3):44-50.
  8. Аврунин А.С., Паршин Л.К., Мельников Б.Е. Критический анализ теории механостата. Клиникопатогенетические аспекты реорганизации архитектуры скелета на разных этапах его развития. Гений ортопедии. 2013; (4):96-102.
  9. Аврунин А.С. Синдром остеомаляции – социальноэкономическая роль клинико-диагностические проблемы. Гений ортопедии. 2014; (2):91-94.
  10. Аврунин А.С. Остеопороз и остеомаляция – клинико-диагностические проблемы. Травматология и ортопедия России. 2014; (4):68-76.
  11. Докторов А.А., Денисов-Никольский Ю.И. Особенности рельефа минерализованной поверхности лакун и канальцев в пластинчатой кости. Бюллетень экспериментальной медицины. 1993; (1):61-65.
  12. Слуцкий Л.И. Биохимия нормальной и патологически измененной костной ткани. Л.: Медицина; 1969. 375 с.
  13. A dachi T., Aonumaa Y., Tairaa K., Hojoa M., Kamiokac H. Asymmetric intercellular communication between bone cells: propagation of the calcium signaling. Biochem Biophys Res Commun. 2009; 389(3):495-500.
  14. A jubi N.E., Klein-Nulend J., Nijweide P.J., Vrijheid-Lammers T., Alblas M.J., Burger E.H. Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes-A cytoskeletondependent process. Biochemical and biophysical research communications. 1996; 225(1131):62-68.
  15. A khter M.P., Cullen D.M., Gong G., Recker R.R. Bone biomechanical properties in prostaglandin EPX and EP2 knockout mice. Bone. 2001; 29(2):121-125.
  16. A kkus O., Yeni Y. N., Wasserman N. Fracture mechanics of cortical bone tissue: a hierarchical perspective. Biomedical Engineering. 2004; 32(5&6):379-425.
  17. A mano K., Miyake K., Borke J.L., McNeil P.L. Breaking biological barriers with a toothbrush. J Dent Res. 2007; 86(8):769-774.
  18. Bacabac R.G., Mizuno D., Schmidt C.F., MacKintosh F.C., Van Loon J.J.W.A., Klein- Nulend J., Smit T.H. Round versus flat: Bone cell morphology, elasticity, and mechanosensing. J Biomechanics. 2008; 41(7):1590- 1598.
  19. Bass M., Ford M.A., Brown B. Mauromoustakos A., Keathley R.S. Variables for the prediction of femoral bone mineral status in american women. Southern Medical J. 2006; 99(2):115- 122.
  20. Baud C.A. Morphologie et structure inframicroscopique des osteocytes. Acta Anat (Basel). 1962; (51):209-225.
  21. Bershadsky A.D., Balaban N.Q., Geiger B. Adhesiondependent cell mechanosensittvity. Annu Rev Cell Dev Biol. 2003; 19:677-695.
  22. Biolo G., Heer M., Narici M., Strollo F. Microgravity as a model of ageing. Current Opinion in Clinical Nutrition Metabolic Care. 2003; 6(1):31-40.
  23. Bleicher K., Cumming R.G., Naganathan V., Blyth F.M., Le Couteur D.G., Handelsman D.J., Waite L.M., Seibel M.J. U- shaped association between serum 25-hydroxyvitamin D and fracture risk in older men: results from the prospective population based champ study. J Bone Mineral Research. 2014; 29(9):2024-2031.
  24. Bloomfield S.A. Contributions of physical activity to bone health over the lifespan. Topics in Geriatric Rehabilitation. 2005; 21(l):68-76.
  25. Bonewald L.F. Osteocytes: A proposed multifunctional bone cell. J Musculoskel Neuron Interact. 2002; 2(3):239-241.
  26. Bretscher A., Edwards K., Fehon R.G. ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002; 3(8):586-599.
  27. Bu S., Chen Y., Wang S., Zhang F., Ji G. Treadmill training regulates b-catenin signaling through phosphorylation of GSK-3 b in lumbar vertebrae of ovariectomized rats. Eur J Appl Physiol. 2012, 112(9):3295-3304.
  28. Burke T.N., Franca F.J.R., de Meneses S.R.F., Pereira R.M.R., Marques A.P. Postural control in elderly women with osteoporosis: comparison of balance, strengthening and stretching exercises. A randomized controlled trial. Clinical Rehabilitation. 2012; 26(11):1021-1031.
  29. Cadena E.A., Schweitzer M.H. Variation in osteocytes morphology vs bone type in turtle shell and their exceptional preservation from the Jurassic to the present. Bone. 2012; 51(3):614- 620.
  30. Castelo-Branco C. Management of osteoporosis. An overview. Drugs & Aging. 1998; 12 Suppl. 1: 25-32.
  31. Chen J.L., Yao W., Frost H.M., Li С.Y., Setterberg R.B., Jee W.S. Bipedal stance exercise enhances antiresorption effects of estrogen and counteracts its inhibitory effect on bone formation in sham and ovariectomized rats. Bone. 2001; 29(2):126-121.
  32. Cowin S.C. Mechanosensation and fluid transport in living bone. J Musculoskel Neuron Interact. 2002; 2(3):1-5.
  33. Currey J. The mechanical adaptations of bones. New Jersey: Princeton University Press; 1984.
  34. de Jong W.C., Koolstra J.H., Korfage J.A.M., van Ruijven L.J., Langenbach G.E.J. The daily habitual in vivo strain history of a non-weight-bearing bone. Bone. 2010; 46(1):196-202.
  35. Dempster D.W. The pathophysiology of bone loss. Clin Geriatr Med. 2003; 19(2):259- 270.
  36. Dodd J.S., Raleigh J.A., Gross T.S. Osteocyte hypoxia: a novel mechanotransduction pathway. Am J Physiol Cell Physiol. 1999; 277(3 Pt 1):598-602.
  37. F eehan L.M., Beck С.A., Harris S.R., MacIntyre D.L., Li L.С. Exercise prescription after fragility fracture in older adults: a scoping review. Osteoporos Int. 2010; 22(5):1289-1322.
  38. F ernandez-Seara M.A., Wehrli S.L., Wehrli F.W. Diffusion of exchangeable water in cortical bone studied by nuclear magnetic resonance. Biophys J. 2002; 82(1). Pt. 1:522- 529.
  39. F riedlander A.L., Genant H.K., Sadowsky S., Byl N.N., Gluer C.-C. A twoyear program of aerobics and weight training enhances bone mineral density of young women. J Bone Mineral Research. 1995; 10(4):574-585.
  40. F ritton S.P., McLeod K.J., Rubin C.T. Quantifying the strain history of bone: spatial uniformity and self-similarity of low-magnitude strains. J Biomech. 2000; 33(3):317- 325.
  41. F rost H.M. In vivo osteocyte death. J Bone Joint Surg Am. 1960; 42(1):138-143.
  42. F rost H.M. Why the ISMNI and the Utah paradigm? Their role in skeletal and extraskeletal disorders. J Musculoskel Neuron Interact. 2000; 1(1):5-9.
  43. F rost H.M., Jee W.S.S. Osteoporosis in 2000 ad: quo vadis? J Musculoskeletal Research. 2001; 5(1):1-16.
  44. Gouleta G.C., Cooper D.M.L., Coombe D., Zernicke R.F. Influence of cortical canal architecture on lacunocanalicular pore pressure and fluid flow. Computer Methods Biomechanics Biomedical Engineering. 2008; 11(4):379-387.
  45. H ardiman D.A., O’Brien F.J., Prendergast P.J., Croke D.T., Staines A., Lee T.C. Tracking the changes in unloaded bone: morphology and gene expression. European J Morphology. 2005; 42(4/5):208-216.
  46. H enderson J.H., Carter D.R. Mechanical induction in limb morphogenesis: the role of growthgenerated strains and pressures. Bone. 2002; 31(6):645-653.
  47. H illsley V., Frangos J.A. Review: bone tissue engineering: the role of interstitial fluid flow. Biotechnology and Bioengineering. 1994; 43(7):573-581.
  48. H olick M.F. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging. 2007; 24(12):1017-1029.
  49. H ooven F.H., Adachi J.D., Adami S., Boonen S., Compston J., Cooper С., Delmas P., Diez- Perez A., Gchlbach S., Greenspan S.L., LaCroix A., Lindsay R., Netelenbos J.С., Pfeilschifter J., Roux C., Saag K.G., Sambrook P., Silverman S., Siris E., Watts N.B., Anderson F.A. The Global Longitudinal Study of Osteoporosis in Women (GLOW): rationale and study design. Osteoporos Int. 2009; 20(7):1107-1116.
  50. H orvai A.E., Boyce B.F. Metabolic bone diseases. Seminars in Diagnostic Pathology. 2011; 28(1):13- 25.
  51. Ishihara Y., Naruse Y.S.K., Yamashiro T., Kamioka H., Kawanabe N., Kurosaka H. In situ imaging of the autonomous intracellular Ca2+ oscillations of osteoblasts and osteocytes in bone. Bone. 2012; 50(4):842-852.
  52. Kanis J.A., McCloskey E.V., Johansson H., Oden A., Melton L.J. III, Khaltaev N. A reference standard for the description of osteoporosis. Bone. 2008; 42(3):467475.
  53. Kemmler W., Engelke K. A critical review of exercise training effects on bone mineral density (BMD) in early postmenopausal women. International SportMed J. 2004; 5(1):67-77.
  54. Kemmler W., von Stengel S., Bebenek M., Engelke K., Hentschke С., Kalender W.A. Exercise and fractures in postmenopausal women: 12year results of the Erlangen Fitness and Osteoporosis Prevention Study (EFOPS). Osteoporos Int. 2012; 23(4):1267-1276.
  55. Khayyeri H., Checa S., Tagil M., Prendergast P.J. Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a latticemodeling approach. J Orthopaedic Research. 2009; 27(12):1659-1666.
  56. Knothe Tate M.L., Niederer P., Knothe U. In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone. 1998; 22(2):107-117.
  57. Lanyon L., Skerry T. Postmenopausal osteoporosis as a failure of bone’s adaptation to functional loading: A- hypothesis. J Bone Mineral Research. 2001; 16(11):1937-1947.
  58. Lewiecki E.M., Bilezikian J.P., Cooper C., Hochberg M.C., Luckey M.M., Maricic M., Miller P.D. Proceedings of the Eighth Annual Santa Fe Bone Symposium, August 34, 2007. J Clinical Densitometry. 2008; 11(2):313- 324.
  59. Li W., You L., Schaffler M.B., Wang L. The dependency of solute diffusion on molecular weight and shape in intact bone. Bone. 2009; 45(5):1017-1023.
  60. Lorich D.G., Brighton C.T., Gupta R., Corsetti J.R., Levine S.E., Gelb I.D., Seldes R., Pollack S.R. Biochemical pathway mediating the response of bone cells to capacitive coupling. Clin Orthop. 1998; (350):246-256.
  61. Martin R.B. On the significance of remodeling space and activation rate changes in bone remodeling. Bone. 1991; 12(6):391-400.
  62. Melton III L.J. Global aspects of osteoporosis epidemiology. Osteoblast function and the mechanism of action of boneforming agents. In: Osteoporosis 1996 : proceedings of the 1996 World Congress on Osteoporosis, Amsterdam, The Netherlands, 18-23 May 1996. p. 79- 86.
  63. Mosley J.R. Osteoporosis and bone functional adaptation: Mechanobiological regulation of bone architecture in growing and adult bone, a review. J Rehabilitation Research Development. 2000; 37(2):189-199.
  64. Mullender M., EI Haj A.J., Yang Y., van Duin M.A., Burger E.H., Klein-Nulend J. Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med Biol Eng Comput. 2004; 42(1):14-21.
  65. Okada S., Yoshida S., Ashrafi S.H., Schraufnagel D.E. he canalicular structure of compact bone in the rat at different ages. Microsc Microanal. 2002; 8(2):104-115.
  66. Orellana-Lezcano M.F., Major P.W., McNeil P.L., Borke J.L., Borke J.L. Temporary loss of plasma membrane integrity in orthodontic tooth movement. Orthod Craniofac Res. 2005; 8(2):106-113.
  67. Prentice A. Vitamin D deficiency: a global perspective. Nutrition Reviews. 2008; 66(Suppl. 2):S153- S164.
  68. Rawlinson S.C.F., Mosley J.R., Suswillo R.F.L., Pitsillides A.A., Lanyon L.E. Calvarial and limb bone cells in organ and monolayer culture do not show the same early responses to dynamic mechanical strain. J Bone Miner Res. 1995; 10(8):1225-1232.
  69. Reilly G.C., Knapp H.F., Stemmer A., Niederer P., Knothe Tate M.L. Investigation of the morphology of the lacunocanalicular system of cortical bone using atomic force microscopy. Ann Biomed Eng. 2001; 29(12):1074- 1081.
  70. Remagen W., Hohling H.J., Hall T.A. Electron microscopical and microprobe observations on the cell sheath of stimulated osteocytes. Calc Tiss Res. 1969; 4(1):60-68.
  71. Rosen C.J., Gallagher J.C. The 2011 IOM report on vitamin D and calcium requirements for North America: clinical implications for providers teating patients with low bone mineral density. J Clinical Densitometry: Assessment of Skeletal Health. 2011; 14(2):79-84.
  72. Rubinacci A., Covini M., Bisogni C., Villa I., Galli M., Palumbo C., Ferretti M., Muglia M.A., Marotti G. Bone as an ion exchange system: evidence for a link between mechanotransduction and metabolic needs. Am J Physiol Endocrinol Metab. 2002; 282(4):E851-E864.
  73. Sharma D., Ciani C., Marin P.A.R., Levy J.D., Doty S.B., Fritton S.P. Alterations in the osteocyte lacunar- canalicular microenvironment due to estrogen deficiency. Bone. 2012; 51(3):488-497.
  74. Skerry T.M., Suswillo R., El Haj A.J., Ali N.N., Dodds R.A., Lanyon L.E. Load- induced proteoglycan orientation in bone tissue in vivo and in vitro. Calcif Tissue Int. 1990; 46(5):318-326.
  75. Skerry T.M. One mechanostat or many? Modifications of the site-specific response of bone to mechanical loading by nature and nurture. J Musculoskelet Neuronal Interact. 2006; 6(2):122-127.
  76. Szollar S.M., Martin E.M.E., Parthemore J.G., Sartoris D.J., Deftos L.J. Demineralization in tetraplegic and paraplegic man over time. Spinal Cord. 1997; 5(4):223- 228.
  77. Tami A.E., Schaffler M.B., Knothe Tate M.L. Probing the tissue to subcellular level structure underlying bone’s molecular sieving function. Biorheology. 2003; 40(6):577-590.
  78. Tfelt- Hansen J., Brown E.M. The calciumsensing receptor in normal physiology and pathophysiology: a review. Crit Rev Clin Lab Sci. 2005; 42(1):35-70.
  79. Tsuzuku S., Ikegami Y., Yabe К. Bone mineral density differences between paraplegic and quadriplegic patients: a crosssectional study. Spinal Cord. 1999; 37(5):358-361.
  80. Turner C.H., Takano Y., Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Mineral Research. 1995; 10(10): 1544-1549.
  81. van der Linden J.C., Day J.S., Verhaar J.A.N., Weinans H. Altered tissue properties induce changes in cancellous bone architecture in aging and diseases. J Biomech. 2004; 37(3):367-374.
  82. Vatsa A., Breuls R.G., Semeins C.M., Salmon P.L., Smit T.H., Klein-Nulend J. Osteocyte morphology in fibula and calvaria – Is there a role for mechanosensing?Bone. 2008; 43(3):452-458.
  83. W ang L., Ciani C., Doty S.B., Fritton S.P. Delineating bone’s interstitial fluid pathway in vivo. Bone. 2004; 34(3):499-509.
  84. W hyte M.P., Thakker R.V. Rickets and osteomalacia. Medicine. 2009; 37(9):483-488.
  85. W u M., Fannin J., Rice K.M., Wang B., Blough E.R. Effect of aging on cellular mechanotransduction. Ageing Research Reviews. 2011; 10(1):1- 15.
  86. Y ang W., Kalajzic I., Lu Y., Guo D., Harris M.A., Gluhak-Heinrich J., Bonewald L.F., Feng J.Q., Rowe D.W., Harris S.E. In vitro and in vivo study on osteocyte-specific mechanical signaling pathways. J Musculoskel Neuron Interact. 2004; 4(4):386-387.

Copyright (c) 2015

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 82474 от 10.12.2021.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies