Regulation of Osteogenesis

  • J. M. Connor


Normally production of bone is restricted to the skeleton. The mechanisms which ensure this are not understood, but insight should be gained by the study of pathological situations in which soft tissue ossification occurs. Similarly, a knowledge of the mechanisms which are concerned with the regulation of normal osteogenesis will no doubt aid understanding of abnormal osteogenesis. In the production of both normal and ectopic bone the initial step is the synthesis of a highly ordered organic matrix. Subsequently this becomes mineralized. Control mechanisms may operate at all stages in this process but are likely to be involved in the initial phases of matrix production. Furthermore, therapy which aims to prevent the formation of ectopic bone needs to prevent this initial matrix synthesis. For these reasons this chapter will concentrate on the factors which can influence the synthetic aspects of bone matrix homeostasis, after briefly considering the origins of osteogenic cells and the normal requirements for ossification.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Altner PC, Grana L, Gordon M (1975) An experimental study on the significance of muscle tissue interposition on fracture healing. Clin Orthop 111: 269–273PubMedGoogle Scholar
  2. Anderson HC (1969) Vesicles associated with calcification in the matrix of epiphyseal cartilage. J Cell Biol 41: 59–72PubMedCentralPubMedGoogle Scholar
  3. Anderson HC (1976) Matrix vesicle calcification. Fed Proc 35: 105–176Google Scholar
  4. Arey LB (1974) Developmental anatomy. A textbook and laboratory manual of embryology, 7th edn. WB Saunders, Philadelphia LondonGoogle Scholar
  5. Aro H, Eerola E, Aho AJ, Penttinen R (1981) Healing of experimental fractures in the denervated limbs of the rat. Clin Orthop 155: 211–217PubMedGoogle Scholar
  6. Ashton BA, Allen TD, Howlett CR, Eaglesom CC, Hattori A, Owen M (1980) Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin Orthop 151: 294–307PubMedGoogle Scholar
  7. Asling CW, Hurley LS (1963) The influence of trace elements on the skeleton. Clin Orthop 27: 213–264PubMedGoogle Scholar
  8. Barzell US, Morecki R, Spigland I (1971) Enchondral (provisional) calcification in vitro. The effect of some metabolic inhibitors. Clin Orthop 78: 191–194Google Scholar
  9. Bassett CAL (1962) Current concepts of bone formation. J Bone Joint Surg [Am] 44: 1217–1244Google Scholar
  10. Bassett CAL, Becker RO (1962) Generation of electric potentials in bone in response to mechanical stress. Science 137: 1063–1064PubMedGoogle Scholar
  11. Bassett CAL, Pawluk RJ, Becker RO (1964) Effects of electric currents on bone in vivo. Nature 204: 652–654PubMedGoogle Scholar
  12. Bassett CAL, Pawluk RJ, Pilla AA (1974) Bone repair by inductively coupled electromagnetic fields. Science 184: 575–577PubMedGoogle Scholar
  13. Baylink D, Wergedal J, Stauffer M (1971) Formation, mineralization and resorption of bone in hypophosphatemic rats. J Clin Invest 50: 2519–2530PubMedCentralPubMedGoogle Scholar
  14. Becker RO (1961) The bioelectric factors in amphibian limb regeneration. J Bone Joint Surg [Am] 43: 643–656Google Scholar
  15. Becker RO (1978) Electrical osteogenesis—pro and con. Calcif Tissue Res 26: 93–97PubMedGoogle Scholar
  16. Becker RO (1979) The significance of electrically stimulated osteogenesis: More questions than answers. Clin Orthop 141: 266–274PubMedGoogle Scholar
  17. Becker RO, Spadaro JA (1972) Electrical Stimulation of partial limb regeneration in mammals. Bull NY Acad Med 48: 627–641Google Scholar
  18. Beighton P (1977) Inherited disorders of the skeleton. Churchill Livingstone, Edinburgh London New YorkGoogle Scholar
  19. Bonucci E, Dearden LC (1976) Matrix vesicles in aging cartilage. Fed Proc 35: 163–168PubMedGoogle Scholar
  20. Brown JB, Harrison P, Smith MA (1978) Oestrogen and pregnanediol excretion through childhood, menarche and first ovulation. J Biosoc Sci [Suppl] 5: 43–62Google Scholar
  21. Bulmer MG (1970) The biology of twinning in man. Clarendon Press, OxfordGoogle Scholar
  22. Buring K (1975) On the origins of cells in heterotopic bone formation. Clin Orthop 110: 293–301PubMedGoogle Scholar
  23. Calhoun NR, Smith JC Jr, Becker KL (1975) The effect of zinc on ectopic bone formation. Oral Surg 39: 698–706PubMedGoogle Scholar
  24. Castle WE (1941) Size inheritance. Am Nat 75: 488–498Google Scholar
  25. Chambers TJ (1978) The cellular basis of bone resorption. Clin Orthop 151: 283–293Google Scholar
  26. Cozen L (1972) Does diabetes delay fracture healing? Clin Orthop 82: 134–140PubMedGoogle Scholar
  27. Crawley RH, McKeown T, Record RG (1955) Parental stature and birth weight. Am J Hum Genet 6: 448–473Google Scholar
  28. Fallon MD, Whyte MP, Teitelbaum SL (1980) Stereospecific inhibition of alkaline phosphatase by L-tetramisole prevents in vitro cartilage calcification. Lab Invest 43: 489–494PubMedGoogle Scholar
  29. Felix R, Fleisch H (1976) Role of matrix vesicles in calcification. Fed Proc 35: 169–171PubMedGoogle Scholar
  30. Fell HB (1956) Skeletal development in tissue culture. In: Bourne GH (ed), The biochemistry and physiology of bone. Academic Press, New York San Francisco London, pp 401–441Google Scholar
  31. Fell HB, Mellanby E (1952) The effect of hypervitaminosis A on embryonic limb bones cultivated in vitro. J Physiol (Lond) 116: 320–349Google Scholar
  32. Fischbein S, Nordqvist T (1978) Profile comparisons of physical growth for monozygotic and dizygotic twin pairs. Ann Hum Biol 4: 417–430Google Scholar
  33. Fishman WH, Ghosh NK (1967) Isoenzymes of human alkaline phosphatase. Adv Clin Chem 10: 255–370Google Scholar
  34. Fleisch H, Russell RGG, Straumann F (1966) Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature 212: 901–903PubMedGoogle Scholar
  35. Frame B, Jackson CE, Reynolds WA, Umphrey JE (1974) Hypercalcemia and skeletal effects of chronic hypervitaminosis A. Ann Intern Med 80: 44–48PubMedGoogle Scholar
  36. Friedenstein AJ (1968) Induction of bone tissue by transitional epithelium. Clin Orthop 59: 21–35PubMedGoogle Scholar
  37. Friedenstein AJ (1973) Determined and inducible osteogenic precursor cells. In: Hard tissue growth, repair and remineralization. Elsevier, New York, pp 169–181 (Ciba Foundation Symposium II)Google Scholar
  38. Galton F (1889) Natural inheritance. Macmillan, London New YorkGoogle Scholar
  39. Graham GG, Adrianzen T (1972) Late ‘catch-up’ growth after severe infantile malnutrition. Johns Hopkins Med J 131: 204–211PubMedGoogle Scholar
  40. Griffiths GC, Nichols G, Asher JD, Flanagan B (1965) Heparin osteoporosis. JAMA 193: 91–94Google Scholar
  41. Habicht J-P, Martorell R, Yarbrough C, Malina RM, Klein RE (1974) Height and weight standards for preschool children. Lancet I: 611–614Google Scholar
  42. Hall BK (1970) Cellular differentiation in skeletal tissues. Biol Rev 45: 455–484PubMedGoogle Scholar
  43. Hall BK (1978) Developmental and cellular skeletal biology. Academic Press, New York San Francisco LondonGoogle Scholar
  44. Hambridge KM, Neidner KH, Walravens PA (1975) Zinc, acrodermatitis enteropathica, and congenital malformations. Lancet I: 577–578Google Scholar
  45. Hamilton WJ, Boyd JD, Mossman HW (1962) Human embryology (prenatal development of form and function), 3rd edn. W Heffer and Sons, CambridgeGoogle Scholar
  46. Harris WH, Travis DF, Friberg U, Radin E (1964) The in vivo inhibition of bone formation by Alizarin Red S. J Bone Joint Surg [Am] 46: 493–508Google Scholar
  47. Harris WH, Lavorgna J, Hamblen DL, Haywood EA (1968) The inhibition of ossification in vivo. Clin Orthop 61: 52–60PubMedGoogle Scholar
  48. Hauspie RC, Das SR, Preece MA, Tanner JM (1982) Degree of resemblance of pattern of growth among sibs in families of West Bengal (India). Ann Hum Biol 9: 171–174PubMedGoogle Scholar
  49. Houston CS (1978) The radiologists’ opportunity to teach bone dynamics. J Can Assoc Radiol 29: 232–238PubMedGoogle Scholar
  50. Hurley LS (1981) Trace metals in mammalian development. Johns Hopkins Med J 148: 1–10PubMedGoogle Scholar
  51. Jameson S (1976) Effects of zinc deficiency in human reproduction. Acta Med Scand [Suppl] 593Google Scholar
  52. Jotereau FV, Le Douarin NM (1978) The developmental relationship between osteocytes and osteoclasts. A study using quail-chick nuclear marker in enchondral ossification. Dev Biol 63: 253–265PubMedGoogle Scholar
  53. Kaitila I, Wartiovaara J, Laitinen O, Saxen L (1970) The inhibitory effect of tetracycline on Osteogenesis in organ culture. J Embryol Exp Morphol 23: 185–211PubMedGoogle Scholar
  54. Kim KK (1976) Calcification of matrix vesicles in human aortic valve and aortic media. Fed Proc 35: 156–162PubMedGoogle Scholar
  55. Kiviluoto O (1976) Use of free fat transplants to prevent epidural scar formation. An experimental study. Acta Orthop Scand [Suppl] 164: 1–75Google Scholar
  56. Kochar DM (1977) Cellular basis of congenital limb deformity induced in mice by vitamin A. Birth Defects 13: 111–154Google Scholar
  57. Langenskiöld A, Kiviluoto O (1976) Prevention of epidural scar formation after operations on the lumbar spine by means of free fat transplants. Clin Orthop 115: 92–95PubMedGoogle Scholar
  58. Lindholm TS, Törnkvist H (1981) Inhibitory effect on bone formation and calcification exerted by the anti-inflammatory drug Ibuprofen. Scand J Rheumatol 10: 38–42PubMedGoogle Scholar
  59. Loutit JF, Nisbet NW (1979) Resorption of bone. Lancet II: 26–28Google Scholar
  60. Mack PB, Lachance PA, Vose GP, Vogt FB (1967) Bone demineralization of foot and hand of Gemini-Titan IV, V, and VII astronauts during orbital flight. AJR 100: 503–511Google Scholar
  61. Malina RM (1969) Exercise as an influence upon growth. Review and critique of current concepts. Clin Pediatr 8: 16–26Google Scholar
  62. Marshall WA (1971) Evaluation of growth rate in height over periods of less than one year. Arch Dis Child 46: 414–420PubMedCentralPubMedGoogle Scholar
  63. Minaire P, Meunier P, Edouard C, Bernard J, Courpron P, Bourret J (1974) Quantitative histological data on disuse osteoporosis—comparison with biological data. Calcif Tissue Res 17: 57–73PubMedGoogle Scholar
  64. Montgomery WW, van Orman P (1967) The inhibitory effect of adipose tissue on osteogenesis. Ann Otol Rhinol Laryngol 76: 988–997PubMedGoogle Scholar
  65. Moore LA, Huffman CF, Duncan CW (1935) Blindness in cattle associated with constriction of the optic nerve and probably of nutritional origin. J Nutr 9: 533–551Google Scholar
  66. Mosier HD Jr, Jansons RA (1970) Effect of x-irradiation on selected areas of the head of the newborn rat on growth. Radiat Res 43: 92–104PubMedGoogle Scholar
  67. Mosier HD Jr, Grossman HJ, Dingman HF (1965) Physical growth in mental defectives. A study in an institutionalized population. Paediatrics 36: 465–519Google Scholar
  68. Ornoy A, Atkin I, Levy J (1980) Ultrastructural studies on the origin and structure of matrix vesicles in bone of young rats. Acta Anat (Basel) 106: 450–461Google Scholar
  69. Owen CA Jr, Tyle GM, Flock EV, McCall JT (1970) Heparin-ascorbic acid antagonism. Mayo Clin Proc 45: 140–145PubMedGoogle Scholar
  70. Owen M (1970) The origin of bone cells. Int Rev Cytol 28: 213–238PubMedGoogle Scholar
  71. Owen M (1977) Precursors of osteogenic cells. Calcif Tissue Res [Suppl] 24: R19Google Scholar
  72. Owen M (1980) The origin of bone cells in the postnatal organism. Arthritis Rheum 23: 1073–1079PubMedGoogle Scholar
  73. Persson B (1980) Insulin as a growth factor in the fetus. In: Ritzen M, Aperia A, Hall K, Larsson A, Zetterberg A, Zetterstrom R (eds), The biology of normal human growth. Raven Press, New York, pp 213–221Google Scholar
  74. Prockop DJ, Kivirikko KI, Tuderman L, Guzman NA (1979) The biosynthesis of collagen and its disorders. N Engl J Med 301: 13–23, 77–85PubMedGoogle Scholar
  75. Raisz LG, Canalis EM, Dietrich JW, Kream BE, Gworek SC (1978) Hormonal regulation of bone formation. Recent Prog Horm Res 34: 335–356PubMedGoogle Scholar
  76. Rasmussen H (1968) The parathyroids. In: Williams RH (ed), Textbook of endocrinology, 4th edn. WB Saunders, Philadelphia, pp 847–965Google Scholar
  77. Rathbun JC, MacDonald JW, Robinson HMC, Wanklin JM (1961) Hypophosphatasia: A genetic study. Arch Dis Child 36: 540–542PubMedCentralPubMedGoogle Scholar
  78. Riekstniece E, Asling CW (1966) Thyroxine augmentation of growth hormone-induced enchondral osteogenesis. Proc Soc Exp Biol Med 123: 258–263PubMedGoogle Scholar
  79. Rimoin DL (1977) Pathogenetic mechanisms of limb malformations in the skeletal dysplasias. Birth Defects 13: 339–353PubMedGoogle Scholar
  80. Riska EB, Michelsson JE (1979) Treatment of para-articular ossification after total hip replacement by excision and use of free fat transplants. Acta Orthop Scand 50: 751–754PubMedGoogle Scholar
  81. Rø J, Sudmann E, Marton PF (1976) Effect of indomethacin on fracture healing in rats. Acta Orthop Scand 47: 588–599Google Scholar
  82. Robinson RA (1979) Bone tissue: Composition and function. Johns Hopkins Med J 145: 10–24PubMedGoogle Scholar
  83. Robison R (1923) The possible significance of hexosephosphoric esters in ossification. Biochem J 17: 286–293PubMedCentralPubMedGoogle Scholar
  84. Rosenquist JB, Baylink DJ, Spengler DM (1977) The effect of beta-aminoproprionitrile (BAPN) on bone mineralization. Proc Soc Exp Biol Med 154: 310–313PubMedGoogle Scholar
  85. Sayegh FS, Solomon GC, Davis RW (1974) Ultrastructure of intracellular mineralization in the Deer’s antler. Clin Orthop 99: 267–284PubMedGoogle Scholar
  86. Schajowicz F, Cabrini RL, Simes RJ, Klein-Szanto AJP (1974) Ultrastructure of chondrosarcoma. Clin Orthop 100: 378–386PubMedGoogle Scholar
  87. Shepard TH (1976) Catalog of teratogenic agents. Johns Hopkins Press, Baltimore LondonGoogle Scholar
  88. Short RV (1980) The hormonal control of growth at puberty. In: Lawrence TW (ed), Growth in animals. Butterworth, London, pp 25–45Google Scholar
  89. Siffert RS (1951) The role of alkaline phosphatase in osteogenesis. J Exp Med 93: 415–425PubMedCentralPubMedGoogle Scholar
  90. Sinclair D (1978) Human growth after birth, 3rd edn, Oxford University Press, London New York TorontoGoogle Scholar
  91. Singh S, Padmanabhan R (1979) Effect of chlorpromazine on skeletogenesis. The result of maternal administration of the drug in experimental rats. Acta Orthop Scand 50: 151–159PubMedGoogle Scholar
  92. Smith DW (1977) Growth and its disorders. WB Saunders, Philadelphia Toronto LondonGoogle Scholar
  93. Smith DW, Truog W, Rogers JE, Greitzer LJ, Skinner AL, McCann JJ, Harvey MAS (1976) Shifting linear growth during infancy: Illustration of genetic factors in growth from fetal life through infancy. J Pediatr 89: 225–230PubMedGoogle Scholar
  94. Smith R (1979) Biochemical disorders of the skeleton. Butterworth, London BostonGoogle Scholar
  95. Spadaro JA (1977) Electrically stimulated bone growth in animals and man. Review of the literature. Clin Orthop 122: 325–332PubMedGoogle Scholar
  96. Tanner JM (1972) Human growth hormone. Nature 237: 433–439PubMedGoogle Scholar
  97. Tanner JM, Whitehouse RH, Hughes PCR, Vince FP (1971) Effect of human growth hormone treatment for 1 to 7 years on growth of 100 children, with growth hormone deficiency, low birth weight, inherited smallness, Turner’s syndrome and other complaints. Arch Dis Child 46: 745–782PubMedCentralPubMedGoogle Scholar
  98. Ten Cate AR, Syrbu S (1974) A relationship between alkaline phosphatase activity and degradation of collagen by the fibroblast. J Anat 117: 351–359Google Scholar
  99. Tonna EA (1966) A study of osteocyte formation and distribution in ageing mice complemented with 3H proline autoradiography. J Gerontol 21: 124–129PubMedGoogle Scholar
  100. Vaughan J (1981) Osteogenesis and haematopoiesis. Lancet II: 133–135Google Scholar
  101. Walton A, Hammond J (1938) The maternal effects on growth and conformation in Shire horse-Shetland pony crosses. Proc R Soc Lond [Biol] 125: 311–335Google Scholar
  102. Weiss P (1950) Perspectives in the field of morphogenesis. Q Rev Biol 25: 177–198PubMedGoogle Scholar
  103. Weston PD, Barrett AJ, Dingle JT (1969) Specific inhibition of cartilage breakdown. Nature 222: 285–287PubMedGoogle Scholar
  104. Winter JSD (1978) Prepubertal and pubertal endocrinology. In: Falkner F, Tanner JM (eds), Human growth. Ballière Tindall, London, pp 183–213Google Scholar
  105. Wood BJ, Robinson GC (1976) Drug induced changes in myositis ossificans progressiva. Pediatr Radiol 5: 40–43PubMedGoogle Scholar
  106. Wyshak G, Frisch RE (1982) Evidence for a secular trend in age of menarche. N Engl J Med 306: 1033–1035PubMedGoogle Scholar
  107. Yasuda I, Noguchi K, Sata T (1955) Dynamic callus and electric callus. J Bone Joint Surg [Am] 37: 1292–1293Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • J. M. Connor
    • 1
  1. 1.Duncan Guthrie Institute of Medical GeneticsYorkhill, GlasgowScotland

Personalised recommendations