Advertisement

Journal of Bone and Mineral Metabolism

, Volume 23, Supplement 1, pp 1–10 | Cite as

The past, present, and future of bone morphometry: its contribution to an improved understanding of bone biology

  • Webster S.S
Invited paper

Abstract

It was not until the 1950s that a better paradigm for bone biology evolved, which led to the birth of bone histomorphometry. Two clinicians, Harold Frost (1958-1964) and Lent Johnson (1964), were responsible for the paradigm stating that the primary function of bone is mechanical load bearing with subsidiary function to participate in plasma calcium homeostasis to support hematopoesis. Dynamic bone histomorphometry was born when Milch et al. (1958) discovered bone localization of tetracycline and Frost generated the methodology to study tetracyclinebased dynamic histological analysis of cortical bone remodeling (1961-1965). Dynamic bone histomorphometry did not blossom until Frost, while a Sun Valley Workshop participant, developed it to address trabecular bone dynamics. The combination of Arnold (1948) producing thin sections of plastic-embedded undecalcified bone and Frost’s (1977-1983) modification of dynamic cortical bone histology for cancellous bone made it possible to study tetracyclinebased dynamic histomorphometry of cancellous bone. It led to the better understanding of basic metabolic unit (BMU) remodelling and to Frost’s mechanostat hypothesis, and characterized the rat model to accelerate the development of several drugs in the treatment of bone diseases. Currently, dynamic bone histomorphometry has contributed to studies in bone’s mechanical usage windows, mechanical usage setpoint hypothesis, muscle-bone relations, marrowbone relations, the Utah paradigm of musculoskeletal physiology, apoptosis, genetics (transgenic mice) and bone structure, bone quality, the lacunocanalicular network and bone modelling, and remodeling hypothesis, osteocyte role as mechanosensory, chemosensory, and regulatory in bone maintenance, targeted and untargeted remodeling, the role of permissive agents, etc., items in bone biology expounded briefly by Lent Johnson (1965) and continuously by Harold Frost at the Sun Valley Workshop (1965-2003). Finally, “What’s next?” covers how to improve and perpetuate the employing of qualitative histomorphometry in research opportunities in hard tissue research.

Key words

Dynamic histomorphometry Skeletal adaptation mechanical usage Mechanostat Utah paradigm skeletal physiology What’s next 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Johnson LC (1962) Joint remodeling as the basis for osteoarthritis. J Am Vet Med Assoc 141:1237Google Scholar
  2. 2.
    Johnson LC (1964) Morphologic analysis in pathology: the kinetics of disease and general biology of bone. In: Frost HM(ed) Bone Biodynamics. Little-Brown, Boston, pp 543–654Google Scholar
  3. 3.
    Johnson LC(1964) Bone density and the relation of structure to function. In: Proceedings, Conference on Aseptic Necrosis of the Femoral Head. Surgery Study Section, NIH, Bethesda, p25Google Scholar
  4. 4.
    Johnson LC(1966) Kinetics of skeletal remodeling. In: Birth Defects. Original Article Series 2:66–142Google Scholar
  5. 5.
    Johnson LC(1971) Genetics and growth. In: Moyers RE, Krogman WM (eds) Craniofacial Growth in Man. Pergamon, New York, pp 258–283Google Scholar
  6. 6.
    Frost HM (1958) Preparation of thin undecalcified bone sections by rapid method. Stain Technol 33:273–277PubMedGoogle Scholar
  7. 7.
    Frost HM (1960) A new bone affection: feathering. J Bone Joint Surg 42A:447–456Google Scholar
  8. 8.
    Frost HM (1960)In vivo osteocyte death. J Bone Joint Surg [Am] 42:138–143Google Scholar
  9. 9.
    Frost HM (1960) Micropetrosis. J Bone Joint Surg 42A:144–150Google Scholar
  10. 10.
    Frost HM (I960) Presence of microscopic cracks in vivo in bone. Henry Ford Hosp Med Bull 8:25–35Google Scholar
  11. 11.
    Frost HM (1963) Introduction to Biomechanics. Thomas, SpringieldGoogle Scholar
  12. 12.
    Frost HM (1964) The Laws of Bone Structure. Thomas, SpringfieldGoogle Scholar
  13. 13.
    Frost HM (1964) Mathematical Elements of Lamellar Bone Remodeling. Thomas, SpringfieldGoogle Scholar
  14. 14.
    Frost HM (1969) Tetracycline-based histological analysis of bone remodeling. Calcif Tissue Res 3:211–237PubMedCrossRefGoogle Scholar
  15. 15.
    Frost HM (1969) Measurement of human bone formation by means of tetracycline labeling. Can J Biochem Physiol 41:331–342Google Scholar
  16. 16.
    Frost HM (1973) The origin and nature of transients in human bone remodeling dynamics. In: Duncan H, Frame B, Parfitt AM (eds) Clinical Aspects of Metabolic Bone Disease. Excerpta Medica, Amsterdam, pp 124–137Google Scholar
  17. 17.
    Frost HM (1977) A method of analysis of trabecular bone dynamics. In: Meunier PJ (ed) Bone Histomorphometry. Armour Montagu, Paris, pp 445–475Google Scholar
  18. 18.
    Frost HM (1977) Bone histomorphometry: empirical correction of appositional rate measurements in trabecular bone. In: Meunier P (ed) Second International Workshop on Bone Morphometry. University of Claude Bernard, Lyon, p 371Google Scholar
  19. 19.
    Frost HM (1977) Bone histomorphometry: a method of analysis of trabecular bone dynamics. In: Meunier P (ed) Second International Workshop on Bone Morphometry. University of Claude Bernard, Lyon, p 445Google Scholar
  20. 20.
    Frost HM(1983) Bone histomorphometry: analysis of trabecular bone dynamics. In: Recker RR (ed) Bone Histomorphometry, Techniques and Interpretations. CRC, Boca Raton, pp 109–142Google Scholar
  21. 21.
    Frost HM (1983) Analysis of trabecular bone dynamics. In: Recker RR. (ed) Bone Histomorphometry: Techniques and Interpretation. CRC, Boca Raton, pp 143–224Google Scholar
  22. 22.
    Frost HM (1985) Bone microdamage: factors that impair its repair. In: Uhthoff HK (ed) Current Concepts in Bone Fragility. Springer, Berlin, pp 123–148Google Scholar
  23. 23.
    Frost HM (1986) Intermediary Organization of the Skeleton, vols I and II. CRC, Boca RatonGoogle Scholar
  24. 24.
    Frost HM (1987) The mechanostat: a proposed pathogenetic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. Bone Miner 2:73–85PubMedGoogle Scholar
  25. 25.
    Frost HM (1987) The mechanostat. Anat Rec 219:1–9PubMedCrossRefGoogle Scholar
  26. 26.
    Frost HM (1960) Introductions to joint biomechanics. Henry Ford Hosp Med Bull 8:415–432PubMedGoogle Scholar
  27. 27.
    Frost HM (1987) Mechanical determinants of bone architecture. I: Bone modeling. In: Albright J A Brand RA (eds) The Scientific Basis of Orthopaedics, 2nd edn. Appleton-Century-Crofts, New York, pp 241–266Google Scholar
  28. 28.
    Frost HM(1987) Osteogenesis imperfecta. The setpoint proposal. Clin Orthop Relat Res 216:280–297PubMedGoogle Scholar
  29. 29.
    Frost HM(1989) Transient-steady state phenomena in microdamage physiology: a proposed algorithm for lamellar bone. Calcif Tissue Int 44:367–381PubMedCrossRefGoogle Scholar
  30. 30.
    Frost HM (1990) Structural adaptations to mechanical usage (SATMU): 1. Redefining Wolffs law: the bone modeling problem. Anat Rec 226:403–413PubMedCrossRefGoogle Scholar
  31. 31.
    Frost HM(1992) Perspectives: Bone’s mechanical usage windows. Bone Miner 19:257–271PubMedCrossRefGoogle Scholar
  32. 32.
    Frost HM (1996) Perspectives: A proposed general model for the mechanostat (suggestions from a new paradigm). Anat Rec 244:139–147PubMedCrossRefGoogle Scholar
  33. 33.
    Frost HM(1998) A brief review for orthopedic surgeons: fatigue damage (microdamage in bone — its determinants and clinical implications).J Orthop Sci 3:272–281PubMedCrossRefGoogle Scholar
  34. 34.
    Frost HM(1998) On rho, a marrow mediator and estrogen: their roles in bone strength amd “mass” in human females, osteopenias and osteoporoses (insights from a new paradigm). J Bone Miner Metab 16:113–123CrossRefGoogle Scholar
  35. 35.
    Frost HM(1998) Osteoporoses: new concepts and some implications for future diagnosis, treatment and research (based on insights from the Utah paradigm). Ernst Schering Research Foundation AG, Berlin, pp 7–57Google Scholar
  36. 36.
    Frost HM(2000) The Utah paradigm of skeletal physiology: an overview of its insights for bone cartilage and collagenous tissue organs. J Bone Miner Metab 18:305–316PubMedCrossRefGoogle Scholar
  37. 37.
    Frost HM (2001) From Wolff’s law to the Utah paradigm: insights about bone physiology and its clinical applications. Anat Rec 262:398–419PubMedCrossRefGoogle Scholar
  38. 38.
    Frost HM (2001) The Utah paradigm on animal models of skeletal disorders: quo vadis? J Musculoskel Neuron Interact 1:185–191Google Scholar
  39. 39.
    Frost HM(2001) Does the anterior cruciate have a modeling threshold? A case for the affirmative. J Musculoskel Neuron Interact 2:131–136Google Scholar
  40. 40.
    Frost HM (2003) Bone’s mechanostat: a 2003 update. Anat Rec 275:1081–1101CrossRefGoogle Scholar
  41. 41.
    Frost HM (2003) On the strength-safety factor (SSF) for loadbearing skeletal organs. J Musculoskel Neuron Interact 3:136–140Google Scholar
  42. 42.
    Frost HM(2004) A 2003 update of bone physiology and Wolff’s law for clinicians. Angle Orthodont 74:3–15PubMedGoogle Scholar
  43. 43.
    Frost HM, Griffith DL, Jee WSS, Kimmel DB, McCandliss RP, Teitelbaum S (1981) Histomorphometric analysis of trabecular bone in renal dialysis patients treated with calcifediol. J Metab Bone Dis Relat Res 2:285–295CrossRefGoogle Scholar
  44. 44.
    Frost HM, Jee WSS (1994) Perspectives: A vital biomechanical model of the endochonral ossification mechanism. Anat Rec 240:435–446PubMedCrossRefGoogle Scholar
  45. 45.
    Frost HM, Jee WSS (1994) Perspectives: Applications of a biomechanical model of the endochondral ossification mechanism Anat Ree 240:447–455CrossRefGoogle Scholar
  46. 46.
    Frost HM, Schönau E (2000) The “muscle-bone unit” in children and adolescents. J Pediatr Endocrinol Metab 13:571–590PubMedGoogle Scholar
  47. 47.
    Frost HM, Villaneuva AR, Roth H, Stanisaolyevic S (1961) Tetracycline bone labeling. J New Drugs, p 206Google Scholar
  48. 48.
    Hattner R, Epker BN, Frost HM (1965) Suggested sequential mode of control of changes in cell behavior in adult bone remodeling. Nature (Lond) 206:489–490CrossRefGoogle Scholar
  49. 49.
    Schiessl H, Frost HM, Jee WSS (1998) Estrogen and bone-muscle strength and mass relationships. Bone 22:1–6PubMedCrossRefGoogle Scholar
  50. 50.
    Brown W, Haglund K (1995) Landmarks interviews. J NIH Res 7:54–59Google Scholar
  51. 51.
    Milch RA, Rall DP, Tobie JE (1957) The bone localization of the tetracycline.J Nat Cancer Inst 19:87–93PubMedGoogle Scholar
  52. 52.
    Amprino R, Marotti G(1964) A topographic quantitative study of bone formation and reconstruction. In: Blackwood HJJ. (ed) Bone and Tooth Symposium. Macmillan, New York, p 21–33Google Scholar
  53. 53.
    Haas HG, Miller J, Schenk RK (1967) Osteomalacia: metabolic and quantitative histologic studies. Clin Orthop 53:213–222PubMedGoogle Scholar
  54. 54.
    Bordier P, Matrajt H, Miravet B, Hioco D (1964) Mesure histologigue de la masse in de la resorption des travees osseuse. Pathol Biol (Paris) 12:1238Google Scholar
  55. 55.
    Bordier PJ, Tun Chot S (1972) Quantitative histology of metabolic bone disease. Clin Endocrinol Metab 1:197–215CrossRefGoogle Scholar
  56. 56.
    Arnold JS(1951) A method of embedding undecalcified bone for histologic sectioning and its application to radioautography. Science 114:178–180PubMedCrossRefGoogle Scholar
  57. 57.
    Arnold JS, Jee WSS (1954)Embedding and sectioning undecalcified bone and its application to radioautography. Stain Technol 29:225–239PubMedGoogle Scholar
  58. 58.
    Arnold JS, Jee WSS (1954) Double tracer radioautographic studies of Ca45 and Ra226 bone deposition. Radiat Res 1:488Google Scholar
  59. 59.
    Parfitt AM(1983) The physiologic and clinical significance of bone histomorphometric data. In: Recker RR(ed) Bone Histomorphometry: Techniques and Interpretations. CRC, Boca Raton, pp 143–224Google Scholar
  60. 60.
    Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols and units. Report of the ASBMR Histomorphometry Committee. J Bone Miner Res 2:595–610PubMedCrossRefGoogle Scholar
  61. 61.
    Recker RR, Barges-Lux MJ (2003) Bone biopsy and histomorphometry in clinical practice. In: Favus MJ (ed) Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism. American Society for Bone and Mineral Research, Washington, DC, pp 213–219Google Scholar
  62. 62.
    Koch JC(1917) The laws of bone architecture. Am J Anat 21:12–23CrossRefGoogle Scholar
  63. 63.
    Thompson DW (1917) On Growth and Form. Cambridge University Press, LondonGoogle Scholar
  64. 64.
    Lanyon LE, Smith RN (1969) Measurement of bone strain in walking animals. Res Vet Sci 10:83–94Google Scholar
  65. 65.
    Frost HM (1995) Introduction to a New Skeletal Physiology, vol I. Bone and Bones. Pajaro Group, Pueblo, COGoogle Scholar
  66. 66.
    Carter R, Harris HW, Vaser R, Caler WE (1981) The mechanical and biological responses of cortical bone toin vivo strain histories. In: Cowin S (ed) Mechanical Properties of Bone. ASME, New YorkGoogle Scholar
  67. 67.
    Cowin SC (1984) Mechanical Properties of Bone. ASME, New YorkGoogle Scholar
  68. 68.
    Forwood MR, Li I, Kelly WL, Bennett MB (2001) Growth hormone is permissive for skeletal adaptation to mechanical loading. J Bone Miner Res 16:2284–2290PubMedCrossRefGoogle Scholar
  69. 69.
    Metz LN, Martin RB, Turner AS (2003) Histomorphometric analysis of the effects of osteocyte density on osteonal morphology and remodeling. Bone 33:753–759PubMedCrossRefGoogle Scholar
  70. 70.
    Burr DB, Martin RB, Schaffler MB, Radin EL (1985) Bone remodeling in response to in vivo fatigue microdamage. Bone 14:103–109Google Scholar
  71. 71.
    Burr DB, Martin RB, Schaffler MB, Radin EL (1985) Bone remodeling in response toin vivo fatigue microdamage. J Biomech 18:189–200PubMedCrossRefGoogle Scholar
  72. 72.
    Bentolila V, Boyce TM, Fyhrie DP, Drumb R, Skerry TM, Schaffler MB (1998) Intracortical bone remodeling in adult rat long bones after fatigue loading. Bone 23:275–281PubMedCrossRefGoogle Scholar
  73. 73.
    Martin RB (2003) Fatigue microdamage as an essential element of bone mechanics and biology. Calcif Tissue Int 73:101–107PubMedCrossRefGoogle Scholar
  74. 74.
    Martin RB, Burr DB (1982) A hypothetical mechanism for the stimulation of osteonal remodeling by fatigue damage. J Biomech 15:137–139PubMedCrossRefGoogle Scholar
  75. 75.
    Noble BS, Peet N, Stevens HY, Brabbs A, Mosley JR, Reilly GC, Reeve J, Skerry TM, Lanyon LE (2003) Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol 284: C934-C943PubMedGoogle Scholar
  76. 76.
    Noble B (2003) Bone microdamage and cell apoptosis. Eur Cell Mater 6:460–455; discussion 455Google Scholar
  77. 77.
    Arnold JS (1964) The quantitation of bone mineralization as an organ and tissue in osteoporosis. In:Pearson OH, Joplin GF (eds) Dynamic Studies of Metabolic Bone Disease. Blackwell, London, pp 59–79Google Scholar
  78. 78.
    Arnold JS (1968) External and trabecular morphologic changes in lumbar vertebrae in aging. In: Progress in Methods of Bone Mineral Measurement. US Government Printing Office, Washington, DC, pp 352–410Google Scholar
  79. 79.
    Burr DB, Hooser M (1995) Alterations to the en bloc basic fuschin staining protocol for the demonstration of microdamage produced in vivo. Bone 17:431–433PubMedCrossRefGoogle Scholar
  80. 80.
    Burr DB, Stafford T (1990) Validity of the bulk-staining technique to separate artifactual from in vivo bone microdamage. Clin Orthop Relat Res 260:305–308PubMedGoogle Scholar
  81. 81.
    Martin RB, Burr DB (1989) Structure, Function and Adaptation of Compact Bone. Raven, New YorkGoogle Scholar
  82. 82.
    Cowin, SC (2001) Bone Mechanics Handbook, 2nd edn. CRC, Boca RatonGoogle Scholar
  83. 83.
    Tomkinson A, Gevers EF, Wit JM, Reeve J, Noble B (1998) The role of estrogen in the control of rat osteocyte apoptosis. J Bone Miner Res l13:1243–1250CrossRefGoogle Scholar
  84. 84.
    Schaffler MB, Choi K, Milgrom C (1995) Aging and matrix microdamage accumulation in human compact bone. Bone 17: 521–525PubMedCrossRefGoogle Scholar
  85. 85.
    Wenzel TE, Schaffler MB, Fyhrie DP (1996) In vivo trabecular microcracks in human vertebral bone. Bone 19:89–95PubMedCrossRefGoogle Scholar
  86. 86.
    Mori S, Burr DB (1993) Increased intracortical remodeling following fatigue damage. Bone 14:203–209CrossRefGoogle Scholar
  87. 87.
    Dunstan CR, Evans RA, Hills E, Wong SYP, Higgs RJED (1990) Bone death in hip fracture in the elderly. Calcif Tissue Int 47:270–275PubMedCrossRefGoogle Scholar
  88. 88.
    Mullender MG, van der Meer DD, Huiskes R, Lips P (1996) Osteocyte density changes in aging and osteoporosis. Bone 18: 109–113PubMedCrossRefGoogle Scholar
  89. 89.
    Tomkinson A, Reeve J, Shaw RW, Noble BS (1997) The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab 82:3128–3135PubMedCrossRefGoogle Scholar
  90. 90.
    Weinstein RS, Nicholas RW, Manolagas SC (2000) Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip.J Clin Endocrinol Metab 85:2907–2912PubMedCrossRefGoogle Scholar
  91. 91.
    O’Brien CA, Jioa D, Plotkin LI, Bellido T, Powers CC, Steward SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145: 1835–1841PubMedCrossRefGoogle Scholar
  92. 92.
    Noble BS, Stevens H, Reeve J, Loveridge N (1995) Apoptosis in normal and pathological human bone. J Bone Miner Res 10:52–64Google Scholar
  93. 93.
    Noble BS, Stevens H, Loveridge N, Reeve J (1997) Identification of apoptotic changes in osteocytes in normal and pathological human bone. Bone 20:273–282PubMedCrossRefGoogle Scholar
  94. 94.
    Verborgt O, Givson GJ, Lundin-Cannon KD, Schaffler MB (1999) Osteocyte apoptosis occurs in association with bone fatigue, microdamage and resorption. Trans Orthop Res Soc 24:551Google Scholar
  95. 95.
    Cowin SC, Moss-Salentijn L, Moss ML (1991) Candidates for the mechanosensory system in bone. J Biomech Eng 113:191–197PubMedCrossRefGoogle Scholar
  96. 96.
    Cowin SC, Weinbaum S, Zeng Y (1995) A case for bone canaliculi as the anatomical site of strain generated potentials. J Biomech 28:1281–1297PubMedCrossRefGoogle Scholar
  97. 97.
    Mullender MG, Hiskes R (1997) Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone? Bone 20:527–532PubMedCrossRefGoogle Scholar
  98. 98.
    Burger EH, Klein-Nulend J, Van der Plas A, Nijweide PJ (1995) Function of osteocytes in bone: their role in mechanotransduction. J Nutr 125(suppl):2020S-2023SPubMedGoogle Scholar
  99. 99.
    Burger EH, Klein-Nulend J (1999) Mechanotransduction in bone: role of the lacuno-canalicular network. FASEB J 13(suppl):S101-S112PubMedGoogle Scholar
  100. 100.
    Burger EH, (2001) Experiments on cell mechanosensitivity: bone cells as mechanical engineers. In: Cowin SC (ed) Bone Mechanics Handbook, 2nd edn, vol 28. CRC, Boca Raton, 1–16Google Scholar
  101. 101.
    Klein-Nulend J, Van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PJ, Burger, EH (1995) Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J 9:441–445PubMedGoogle Scholar
  102. 102.
    Marotti G, Delrio N, Marotti F, Fadda M (1979) Quantitative analysis of the bone destroying activity of osteocytes and osteoclasts in experimental disuse osteoporosis. Ital J Orthop Traumatol 5:225–240PubMedGoogle Scholar
  103. 103.
    Marotti G, Ferretti M, Muglio MA, Palumbo C, Palazzini SA(1990) A quantitative evaluation of osteoblast-osteocyte relationships on growing endosteal surfaces of rabbit tibia. Bone 13:363–368CrossRefGoogle Scholar
  104. 104.
    Marotti G, Cane V, Palazzini S, Palumbo C (1990) Structurefunction relationships in the osteocyte. Ital J Miner Electrol Metab 4:93–106Google Scholar
  105. 105.
    Marotti G, Ferritti M, Remaggi F, Palumbo C (1995) Quantitative evaluation on osteocyte canalicular density in human secondary osteons. Bone 16:125–128PubMedCrossRefGoogle Scholar
  106. 106.
    Marotti G (1996) The structure of bone tissues and the cellular control of their deposition. Ital J Anat Embryol 101:25–79PubMedGoogle Scholar
  107. 107.
    Martin RB (2000) Toward a unifying theory of bone remodeling. Bone 26:1–6PubMedCrossRefGoogle Scholar
  108. 108.
    Maejuma-Ikeda A, Aoki M, Tsuritani K, Kamioka K, Hiura K, Miyoshi T, Hara H, Takano-Yamamoto T, Kumegawa M (1997) Chick osteocyte-derived protein inhibits osteoclastic bone resorption. Biochem J 322: 245–250Google Scholar
  109. 109.
    Gowen LC, Petersen DN, Mansolf Al, Qi H, Stocks JL, Tkalcevic GT, Simmons HA, Crawford DT, Chidsey-Frink KL, Ke HZ, McNeish JD, Brown TA (2003) Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem 278:1998–2007PubMedCrossRefGoogle Scholar
  110. 110.
    Lowik C, TenDyke P, Van Bezooyen R (2004) Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonists. Calcif Tissue Int 74(suppl):522Google Scholar
  111. 111.
    Gluhak-Heinrich J, Ye L, Bonewald LF, Feng JQ, MacDougall M, Harris SE, Pavlin D (2003) Mechanical loading stimulates dentin matrix protein 1 ((DMP1) expression in osteocytesin vivo. J Bone Miner Res 18:807–817PubMedCrossRefGoogle Scholar
  112. 112.
    Fazzalari NL, Forwood MR, Smith K, Manthey BA, Herseen P (1998) Assessment of cancellous bone quality in severe osteoarthrosis: bone mineral density, mechanics and microdamage. Bone 22:381–38PubMedCrossRefGoogle Scholar
  113. 113.
    Fazzalari NL, Kuliwaba JS, Forwood MR (2002) Cancellous bone microdamage in the proximal femure: influence of age and osteoarthritis on damage morphology and regional distribution. Bone 31:697–702PubMedCrossRefGoogle Scholar
  114. 114.
    Rodan GA, Martin TJ (1981) Role of osteoblasts in hormonal control of bone resorption: a hypothesis. Calcif Tissue Int 33:349–351PubMedCrossRefGoogle Scholar
  115. 115.
    Evert V (2004) Bone lining cells and the regulation of bone resorption. Calcif Tissue Int 74:524Google Scholar
  116. 116.
    Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, Toyama Y, Bonewald LF, Kudo A (1999) Identification and characterization of a novel protein periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta. J Bone Miner Res 14:1239–1249PubMedCrossRefGoogle Scholar
  117. 117.
    Heino TJ, Hentunen TA, Vaananen HK (2002) Ostocytes inhibit osteoclastic bone resorption through transforming growth factorbeta: enhancement by estrogen. J Cell Biochem 85:185–197PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Radiobiology DivisionUniversity of Utah School of MedicineSalt Lake CityUSA

Personalised recommendations