Advertisement

Physiology of Bone Formation, Remodeling, and Metabolism

Chapter

Abstract

Bone, a highly specialized supporting framework of the body, is characterized by its rigidity and hardness and is endowed with the power of regeneration and repair. Its formation is carried out by osteoprogenitor cells powered by Wnt pathway by two important methods, namely, intramembranous ossification, wherein bone is laid down into the primitive connective tissue (mesenchyme) resulting in the formation of bones as seen in skull, clavicle, and mandible, while endochondral ossification is characterized by a cartilage model which acts as a precursor as in femur, tibia, humerus, and radius. To meet the requirements of skeletal growth and mechanical function, bone undergoes dynamic remodeling by a coupled process of bone resorption by osteoclasts and reformation by osteoblasts.

Bone metabolism is under constant regulation by a host of hormonal and local factors. The calcitropic hormones, namely, parathyroid hormone, vitamin D, and calcitonin, affect the bone metabolism the most in addition to other hormones like insulin, growth hormone, gonadal hormones, cytokines, and growth factors.

The bone metabolism can be monitored by markers such as alkaline phosphatase and urinary hydroxyproline. Other markers include products associated with bone formation, such as osteocalcin, osteonectin, and N- and C-terminal pro-peptides of type I collagen, or with bone resorption, namely, acid phosphatase, free gamma-carboxyglutamate, and hydroxylysine glycosides, especially galactosyl hydroxylysine.

Keywords

Bone Formation Bone Resorption Bone Remodel Bone Matrix Ossification Center 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Asagiri M, Takayanagi H (2007) The molecular understanding of osteoclast differentiation. Bone 40:251–264PubMedCrossRefGoogle Scholar
  2. Baylink DJ, Finkelman RD, Mohan S (1993) Growth factors to stimulate bone formation. J Bone Miner Res 8:565–572CrossRefGoogle Scholar
  3. Blair HC, Teitebaum SL, Ghiselli R et al (1989) Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 245:855–857PubMedCrossRefGoogle Scholar
  4. Bonewald LF (1999) Establishment and characterization of an osteocyte-like cell line, MLO-Y4. J Bone Miner Metab 17:61–65PubMedCrossRefGoogle Scholar
  5. Bonewald LF, Dallas SL (1994) Role of active and latent transforming growth factor-β in bone formation. J Cell Biochem 55:350–357PubMedCrossRefGoogle Scholar
  6. Bonewald LF, Mundy GR (1990) Role of transforming growth factor beta in bone remodeling. Clin Orthop Relat Res 2S:35–40Google Scholar
  7. Boulpaep EL, Boron WF (2005) Medical physiology: a cellular and molecular approach. Saunders, Philadelphia, pp 1089–1091Google Scholar
  8. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342PubMedCrossRefGoogle Scholar
  9. Brighton CT, Hunt RM (1986) Histochemical localization of calcium in the fracture callus with potassium pyroantimonate: possible role of chondrocyte mitochondrial calcium in callus calcification. J Bone Joint Surg 68-A:703–715Google Scholar
  10. Brighton CT, Hunt RM (1991) Early histological and ultrastructural changes in medullary fracture callus. J Bone Joint Surg 73-A:832–847Google Scholar
  11. Brighton CT, Sugioka Y, Hunt RM (1973) Cytoplasmic structures of epiphyseal plate chondrocytes; quantitative evaluation using electron micrographs of rat costochondral junctions with specific reference to the fate of hypertrophic cells. J Bone Joint Surg 55:771–784PubMedGoogle Scholar
  12. Brodsky B, Persikov AV (2005) Molecular structure of the collagen triple helix. Adv Protein Chem 70:301–339PubMedCrossRefGoogle Scholar
  13. Bruzzaniti A, Baron R (2007) Molecular regulation of osteoclast activity. Rev Endocr Metab Disord 7: 123–139CrossRefGoogle Scholar
  14. Burr DB (2002) Targeted and nontargeted remodeling. Bone 30:2–4PubMedCrossRefGoogle Scholar
  15. Cadigan KM, Liu YI (2006) Wnt signaling: complexity at the surface. J Cell Sci 119:395–402PubMedCrossRefGoogle Scholar
  16. Caetano-Lopes J, Canhao H, Fonseca JE (2007) Osteoblasts and bone formation. Acta Reumatol Port 32:103–110PubMedGoogle Scholar
  17. Canalis E, McCarthy TL, Centrella M (1989) The role of growth factors in skeletal remodeling. Endocrinol Metab Clin North Am 18:903–918PubMedGoogle Scholar
  18. Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24:218–235PubMedCrossRefGoogle Scholar
  19. Charles JM, Key LL (1998) Developmental spectrum of children with congenital osteopetrosis. J Pediatr 132:371–374PubMedCrossRefGoogle Scholar
  20. Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3:S131–S139PubMedCrossRefGoogle Scholar
  21. Cohen MM Jr (2006) The new bone biology: pathologic, molecular, clinical correlates. Am J Med Genet A 140:2646–2706PubMedGoogle Scholar
  22. Cohick WS, Clemmons DR (1993) The insulin-like growth factors. Annu Rev Physiol 55:131–153PubMedCrossRefGoogle Scholar
  23. Compston JE (2001) Sex steroids and bone. Physiol Rev 81:419–447PubMedGoogle Scholar
  24. Conover CA (2008) Insulin-like growth factor-binding proteins and bone metabolism. Am J Physiol Endocrinol Metab 294:10–14CrossRefGoogle Scholar
  25. Deftos LJ (1998) Calcium and phosphate homeostasis, chapter 2. In: Clinical essentials of calcium and skeletal metabolism, 1st edn. Professional Communication Inc., pp 1–208. http://www.endotext.org/parathyroid/parathyroid2/ch01s05.html. Accessed 20 Apr 2011
  26. Deftos LJ (2001) Immunoassays for PTH and PTHrP, chapter 9. In: Bilezikian JP, Marcus R, Levine A (eds) The parathyroids, 2nd edn. Academic Press, San Diego,pp 143–166CrossRefGoogle Scholar
  27. Deftos LJ, Gagel R (2000) Calcitonin and medullary thyroid carcinoma, chapter 265. In: Wyngarden JB, Bennett JC (eds) Cecil textbook of medicine, 21st edn. WB Saunders Company, Philadelphia, pp 1406–1409Google Scholar
  28. Delmas PD (1995) Biochemical markers for the assessment of bone turnover. In: Riggs BL, Melton J (eds) Osteoporosis: etiology, diagnosis, and management, 2nd edn. Lippincott-Raven, PhiladelphiaGoogle Scholar
  29. Dempster DW, Cosman F, Parisien M et al (1993) Anabolic actions of parathyroid hormone on bone. Endocr Rev 14:690–709PubMedGoogle Scholar
  30. Eriksen EF (1986) Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr Rev 7:379–408PubMedCrossRefGoogle Scholar
  31. Eriksen EF, Axelrod DW, Melsen F (1994) Bone histomorphometry. Raven Press, New York, pp 1–12Google Scholar
  32. Fernández-Tresguerres-Hernández-Gil I, Alobera-Gracia MA, del Canto-Pingarrón M et al (2006) Physiological bases of bone regeneration II. The remodeling process. Med Oral Patol Oral Cir Bucal 11:E151–E157PubMedGoogle Scholar
  33. Fraher L (1993) Biochemical markers of bone turnover. Clin Biochem 26:431–432PubMedCrossRefGoogle Scholar
  34. Gallagher SK (1997) Biochemical markers of bone metabolism as they relate to osteoporosis. MLO: Med Lab Obs 29(8):50. FindArticles.com.
  35. Gori F, Hofbauer LC, Dunstan CR et al (2000) The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated. Endocrinology 141:4768–4776PubMedCrossRefGoogle Scholar
  36. Grant SFA, Ralston SH (1997) Genes and osteoporosis. Endocrinology 8:232–239Google Scholar
  37. Hakeda Y, Kawaguchi H, Hurley M et al (1996) Intact insulin-like growth factor binding protein-5 (IGFBP-5) associates with bone matrix and the soluble fragments of IGFBP-5 accumulated in culture medium of neonatal mouse calvariae by parathyroid hormone and prostaglandin E2-treatment. J Cell Physiol 166:370–379PubMedCrossRefGoogle Scholar
  38. Harada S, Rodan GA (2003) Control of osteoblast function and regulation of bone mass. Nature 423: 349–355PubMedCrossRefGoogle Scholar
  39. Harvey S, Hull KL (1998) Growth hormone: a paracrine growth factor? Endocrine 7:267–279CrossRefGoogle Scholar
  40. Hill PA, Reynolds JJ, Meikle MC (1995) Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. Endocrinology 136:124–131PubMedCrossRefGoogle Scholar
  41. Hock JM, Centrella M, Canalis E et al (2004) Insulin-like growth factor I (IGF-I) has independent effects on bone matrix formation and cell replication. Endocrinology 122:254–260CrossRefGoogle Scholar
  42. Hofbauer LC, Khosla S, Dunstan CR et al (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140:4367–4370PubMedCrossRefGoogle Scholar
  43. Horowitz M (2003) Matrix proteins versus cytokines in the regulation of osteoblast function and bone formation. Calcif Tissue Int 72:5–7PubMedCrossRefGoogle Scholar
  44. Horwood NJ, Elliott J, Martin TJ et al (1998) Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139:4743–4746PubMedCrossRefGoogle Scholar
  45. Kawaguchi H, Pilbeam CC, Raisz LG (1994) Anabolic effects of 3,3′,5- triiodothyronine and triiodothyroacetic acid in cultured neonatal mouse parietal bones. Endocrinology 135:971–976PubMedCrossRefGoogle Scholar
  46. Kawaguchi H, Pilbean CC, Harrison JR et al (1995) The role of prostaglandins in the regulation of bone metabolism. Clin Orthop 313:36–46PubMedGoogle Scholar
  47. Knelles D, Barthel T, Kraus U et al (1997) Randomized trial comparing early postoperative irradiation vs. the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement. Int J Radiat Oncol Biol Phys 39:961–966PubMedCrossRefGoogle Scholar
  48. Kobayashi S, Takahashi HE, Ito A et al (2003) Trabecular minimodeling in human iliac bone. Bone 32:163–169PubMedCrossRefGoogle Scholar
  49. Krishnan V, Bryant HU, Macdougald OA et al (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209PubMedCrossRefGoogle Scholar
  50. Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRefGoogle Scholar
  51. Lind M, Deleuran B, Thestrup-Pedersen K et al (1995) Chemotaxis of human osteoblasts. Effects of osteotropic growth factors. APMIS 103:140–146PubMedCrossRefGoogle Scholar
  52. Lindsay R, Cosman F, Zhou H et al (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest biopsy: early actions of teriparatide. J Bone Miner Res 21:366–373PubMedCrossRefGoogle Scholar
  53. Locklin RM, Oreffo RO, Triffitt JT et al (1999) Effects of TGFbeta and bFGF on the differentiation of human bone marrow stromal fibroblasts. Cell Biol Int 23:185–194PubMedCrossRefGoogle Scholar
  54. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810PubMedCrossRefGoogle Scholar
  55. Lorenzo JA (1992) The role of cytokines in the regulation of local bone resorption. Crit Rev Immunol 11:195–213Google Scholar
  56. Lukert BP, Kream BE (1996) Clinical and basic aspects of glucocorticoid action in bone. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology. Academic, San Diego, pp 533–548Google Scholar
  57. Mackie EJ (2003) Osteoblasts: novel roles in orchestration of skeletal architecture. Int J Biochem Cell Biol 35:1301–1305PubMedCrossRefGoogle Scholar
  58. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21:115–137PubMedCrossRefGoogle Scholar
  59. Marie PJ (2003) Fibroblast growth factor signaling controlling osteoblast differentiation. Gene 316:23–32PubMedCrossRefGoogle Scholar
  60. Mills BG, Frausto A (1997) Cytokines expressed in multinucleated cells: Paget’s disease and giant cell tumors versus normal bone. Calcif Tissue Int 61:16–21PubMedCrossRefGoogle Scholar
  61. Mohan S, Baylink DJ (1991) Bone growth factors. Clin Orthop 263:30–48PubMedGoogle Scholar
  62. Mohanty M (1996) Cellular basis for failure of joint prosthesis. Biomed Mater Eng 6:165–172PubMedGoogle Scholar
  63. Nash TJ, Howlett CR, Martin C et al (1994) Effects of platelet-derived growth factor on tibial osteotomies in rabbits. Bone 15:203–208PubMedCrossRefGoogle Scholar
  64. Netter FH (1987) Musculoskeletal system: anatomy, physiology, and metabolic disorders. Ciba-Geigy Corporation, Summit, pp 129–130. ISBN 0914168886Google Scholar
  65. Papanicolaou DA, Wilder RL, Manolagas SC et al (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128:127–137PubMedGoogle Scholar
  66. Parfitt AM (2002) Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone 30:5–7PubMedCrossRefGoogle Scholar
  67. Plotkin LI, Manolagas SC, Bellido T (2002) Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem 277:8648–8657PubMedCrossRefGoogle Scholar
  68. Plotkin LI, Aguirre JI, Kousteni S et al (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280:7317–7325PubMedCrossRefGoogle Scholar
  69. Pocock NA, Eisman JA, Hopper JL et al (1987) Genetic determinants of bone mass in adults: a twin study. J Clin Invest 80:706–710PubMedCrossRefGoogle Scholar
  70. Raisz LG (1993) Bone cell biology: new approaches and unanswered questions. J Bone Miner Res 8:457–465CrossRefGoogle Scholar
  71. Raisz LG (1997) The osteoporosis revolution. Ann Intern Med 126:458–462PubMedGoogle Scholar
  72. Raisz LG (1999) Physiology and pathophysiology of bone remodeling. Clin Chem 45:1353–1358PubMedGoogle Scholar
  73. Reddy SV (2004) Regulatory mechanisms operative in osteoclasts. Crit Rev Eukaryot Gene Expr 14:255–270PubMedCrossRefGoogle Scholar
  74. Roodman GD (1999) Cell biology of the osteoclast. Exp Hematol 27:1229–1241PubMedCrossRefGoogle Scholar
  75. Roodman GD, Kurihara N, Ohsaki Y et al (1992) Interleukin-6: a potential autocrine/paracrine agent in Paget’s disease of bone. J Clin Invest 89:46–52PubMedCrossRefGoogle Scholar
  76. Rosen CJ, Donahue LR (1998) Insulin-like growth factors and bone – the osteoporosis connection revisited. Proc Soc Exp Biol Med 219:1–7PubMedGoogle Scholar
  77. Sakou T (1998) Bone morphogenetic proteins: from basic studies to clinical approaches. Bone 22:591–603PubMedCrossRefGoogle Scholar
  78. Schneider GB, Key LL, Popoff SN (1998) Osteopetrosis. Therapeutic strategies. Endocrinologist 8:409–417CrossRefGoogle Scholar
  79. Siris ES (1998) Paget’s disease of bone. J Bone Miner Res 13:1061–1065PubMedCrossRefGoogle Scholar
  80. Suda T, Takahashi N, Udagawa N et al (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357PubMedCrossRefGoogle Scholar
  81. Taichman RS (2005) Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem cell niche. Blood 105:2631–2639PubMedCrossRefGoogle Scholar
  82. Teitelbaum SL, Ross FP (2003) Genetic regulation of osteoclast development and function. Nat Rev Genet 4:638–649PubMedCrossRefGoogle Scholar
  83. Teitelbaum SL, Abu-Amer Y, Ross FP (1995) Molecular mechanisms of bone resorption. J Cell Biochem 59:1–10PubMedCrossRefGoogle Scholar
  84. Theill LE, Boyle WJ, Penninger JM (2002) RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 20:795–823PubMedCrossRefGoogle Scholar
  85. Trueta J (1963) The role of blood vessels in osteogenesis. J Bone Joint Surg Br 45:402Google Scholar
  86. Turner CH (1998) Three rules for bone adaptation to mechanical stimuli. Bone 23:339–409CrossRefGoogle Scholar
  87. Ubara Y, Fushimi T, Tagami T et al (2003) Histomorphometric features of bone in patients with primary and secondary hyperparathyroidism. Kidney Int 63:1809–1816PubMedCrossRefGoogle Scholar
  88. Ubara Y, Tagami T, Nakanishi S et al (2005) Significance of minimodeling in dialysis patients with adynamic bone disease. Kidney Int 68:833–839PubMedCrossRefGoogle Scholar
  89. Vaananen HK, Zhao H, Mulari M et al (2000) The cell biology of osteoclast function. J Cell Sci 113:377–381PubMedGoogle Scholar
  90. Wheeless CR. http://www.wheelessonline.com/ortho/bone_remodeling. Accessed 20 Apr 2011
  91. Whyte MP (1994) Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev 15:439–461PubMedGoogle Scholar
  92. Xing L, Boyce BF (2005) Regulation of apoptosis in osteoclasts and osteoblastic cells. Biochem Biophys Res Commun 328:709–720PubMedCrossRefGoogle Scholar
  93. Yamaguchi A, Komori T, Suda T et al (2000) Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev 21:393–411PubMedCrossRefGoogle Scholar
  94. Yasuda H, Shima N, Nakagawa N et al (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/ osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95:3597–3602PubMedCrossRefGoogle Scholar
  95. Young MF (2003) Bone matrix proteins: more than markers. Calcif Tissue Int 72:2–4PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of PathologySt. John’s Medical College and HospitalKoramangala, BangaloreIndia

Personalised recommendations