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Normal Bone Physiology

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Vertebral Compression Fractures in Osteoporotic and Pathologic Bone

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Abstract

The development and remodeling of bone is a complex process that starts early in embryology and continues throughout life and undergoes differences in composition based on the age. The primary cells that are involved in the process are osteoclasts, osteoblasts, and osteocytes which are regulated by numerous signaling molecules and work in concert to form both the organic and inorganic makeup of bone. This chapter will focus on each of these key points in detail as well as give updates on bone physiology.

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References

  1. Musculoskeletal system. In: Standring S, editors. Gray’s anatomy. 39th ed. New York: Elsevier; 2004. pp. 83–135.

    Google Scholar 

  2. Eriksen EF, Axelrod DW, Melsen F. Bone histomorphometry. New York: Raven Press; 1994. p. 1–12.

    Google Scholar 

  3. Kobayashi S, Takahashi HE, Ito A, Saito N, Nawata M, Horiuchi H, Ohta H, Ito A, Iorio R, Yamamoto N, Takaoka K. Trabecular minimodeling in human iliac bone. Bone. 2003;32:163–9.

    Article  CAS  PubMed  Google Scholar 

  4. Van Oers RFM, Wang H, Bacabac RG. Osteocyte shape and mechanical loading. Curr Osteoporos Rep. 2015;13(2):61–6.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337–42.

    Article  CAS  PubMed  Google Scholar 

  6. Tondravi MM, McKercher SR, Anderson K, Erdmann JM, Quiroz M, Maki R, Teitelbaum SL. Osteopetrosis in mice lacking haematopoietic transcription factor PU.1. Nature. 1997;386(6620):81–4.

    Article  CAS  PubMed  Google Scholar 

  7. Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 1994;266(5184):443–8.

    Article  CAS  PubMed  Google Scholar 

  8. Luchin A, Purdom G, Murphy K, Clark MY, Angel N, Cassady AI, Hume DA, Ostrowski MC. The microphthalmia transcription factor regulates expression of the tartrate-resistant acid phosphatase gene during terminal differentiation of osteoclasts. J Bone Miner Res. 2000;15(3):451–60.

    Article  CAS  PubMed  Google Scholar 

  9. Ross FP, Teitelbaum SL. V3 and macrophage colony-stimulating factor: Partners in osteoclast biology. Immunol Rev. 2005;208:88–105.

    Article  CAS  PubMed  Google Scholar 

  10. Teitelbaum SL, Abu-Amer Y, Ross FP. Molecular mechanisms of bone resorption. J Cell Biochem. 1995;59:1–10.

    Article  CAS  PubMed  Google Scholar 

  11. Vaananen HK, Zhao H, Mulari M, Halleen JM. The cell biology of osteoclast function. J Cell Sci. 2000;113:377–81.

    CAS  PubMed  Google Scholar 

  12. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89(5):755–64.

    Article  CAS  PubMed  Google Scholar 

  13. Karsenty G. Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet. 2008;9:183–96.

    Article  CAS  PubMed  Google Scholar 

  14. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1990;284:143–7.

    Article  Google Scholar 

  15. Rubin CT, Lanyon LE. Osteoregulatory nature of mechanical stimuli: function as a determinant for adaptive bone remodeling. J Orthop Res. 1987;5:300–10.

    Article  CAS  PubMed  Google Scholar 

  16. Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T. Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extra- cellular signal-regulated kinase activation. J Biol Chem. 2005;280:7317–25.

    Article  CAS  PubMed  Google Scholar 

  17. Maggioli C, Stagi S. Bone modeling, remodeling, and skeletal health in children and adolescents: mineral accrual, assessment and treatment. Ann Pediatr Endocrinol Metab. 2017;22(1):1–5.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bachrach LK. Acquisition of optimal bone mass in childhood and adolescence. Trends Endocrinol Metab. 2001;12:22–8.

    Article  CAS  PubMed  Google Scholar 

  19. Hemmatian H, Bakker AD, Klein-Nulend J, van Lenthe GH. Aging, osteocytes, and mechanotransduction. Curr Osteoporos Rep. 2017;15(5):401–11.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Klein-nulend J, Van Oers RFM, Bakker AD, Bacabac RG. Bone cell mechanosensitivity, estrogen deficiency, and osteoporosis. J Biomech. 2015;48(5):855–65.

    Article  PubMed  Google Scholar 

  21. Burr DB. Targeted and nontargeted remodeling. Bone. 2002;30:2–4.

    Article  CAS  PubMed  Google Scholar 

  22. Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. 2002;30:5–7.

    Article  CAS  PubMed  Google Scholar 

  23. Klein-Nulend J, Bakker AD, Bacabac RG, Vatsa A, Weinbaum S. Mechanosensation and transduction in osteocytes. Bone. 2013;54(2):182–90.

    Article  CAS  PubMed  Google Scholar 

  24. Babaji P, Devanna R, Jagtap K, et al. The cell biology and role of resorptive cells in diseases: a review. Ann Afr Med. 2017;16(2):39–45.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285(33):25103–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Clarke B. Normal bone physiology. Clin J Am Soc Nephrol. 2008;3:S131–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kim JH, Jin HM, Kim K, Song I, Youn BU, Matsuo K, Kim N. The mechanism of osteoclast differentiation induced by IL-1. J Immunol. 2009;183:1862–70.

    Article  CAS  PubMed  Google Scholar 

  28. Amarasekara DS, Yun H, Kim S, Lee N, Kim H, Rho J. Regulation of osteoclast differentiation by cytokine networks. Immune Netw. 2018;18:450–2.

    Article  Google Scholar 

  29. Silver IA, Murrills RJ, Etherington DJ. Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res. 1988;175:266–76.

    Article  CAS  PubMed  Google Scholar 

  30. Reddy SV. Regulatory mechanisms operative in osteoclasts. Crit Rev Eukaryot Gene Expr. 2004;14:255–70.

    Article  CAS  PubMed  Google Scholar 

  31. Everts V, Delaissé JM, Korper W, Jansen DC, Tigchelaar-Gutter W, Saftig P, Beertsen W. The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res. 2002;17(1):77–90.

    Article  CAS  PubMed  Google Scholar 

  32. Hock JM, Centrella M, Canalis E. Insulin-like growth factor IGF-I has independent effects on bone matrix formation and cell replication. Endocrinology. 2004;122:254–60.

    Article  Google Scholar 

  33. Locklin RM, Oreffo RO, Triffitt JT. Effects of TGFbeta and bFGF on the differentiation of human bone marrow stromal fibroblasts. Cell Biol Int. 1999;23:185–94.

    Article  CAS  PubMed  Google Scholar 

  34. Martin TJ, Sims NA. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005;11:76–81.

    Article  CAS  PubMed  Google Scholar 

  35. Robey P, Boskey A. In: Rosen C, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 7th ed. 2008. pp. 32–8.

    Google Scholar 

  36. Chiquet M, Birk DE, Bönnemann CG, Koch M. Molecules in focus: Collagen XII: protecting bone and muscle integrity by organizing collagen fibrils. Int J Biochem Cell Biol. 2014;53:51–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rosset EM, Bradshaw AD. SPARC/osteonectin in mineralized tissue. Matrix Biol. 2016;52:78–87.

    Article  PubMed  CAS  Google Scholar 

  38. Landis WJ. The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix. Bone. 1995;16:533–44.

    Article  CAS  PubMed  Google Scholar 

  39. Kikuta J, Iwai K, Saeki Y, Ishii M. S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis. Rheumatol Int. 2011;31:967–9.

    Article  CAS  PubMed  Google Scholar 

  40. Lotinun S, Kiviranta R, Matsubara T, Alzate JA, Neff L, Luth A, et al. Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest. 2013;123:666–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Keller J, Catala-Lehnen P, Huebner AK, et al. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat Commun. 2014;5:5215.

    Article  CAS  PubMed  Google Scholar 

  42. Jules J, Yang S, Chen W, Li Y-P. Role of regulators of G protein signaling proteins in bone physiology and pathophysiology. Prog Mol Biol Transl Sci. 2015;133:47–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kode A, et al. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J Clin Invest. 2012;122:3490–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zofkova I, Matucha P. New insights into the physiology of bone regulation: the role of neurohormones. Physiol Res. 2014;63:421–7.

    CAS  PubMed  Google Scholar 

  45. Hamrick MW, Ferrari SL. Leptin and the sympathetic connection of fat to bone. Osteoporos Int. 2008;19:905–12.

    Article  CAS  PubMed  Google Scholar 

  46. Motyl KJ, Rosen CJ. Understanding leptin-dependent regulation of skeletal homeostasis. Biochemie. 2012;94:2089–96.

    Article  CAS  Google Scholar 

  47. Matic I, et al. Bone-specific overexpression of NPY modulates osteogenesis. J Musculoskelet Neuronal Interact. 2012;12:209–18.

    CAS  PubMed  Google Scholar 

  48. Franguinho F, Liz MA, Nunes AF, Neto E, Lamghari M, Sousa MM. Neuropeptide Y and osteoblast differentiation-the balance between the neuro-osteogenic network and local control. FEBS J. 2010;277:3664–7.

    Article  CAS  Google Scholar 

  49. Albright F, Smith PH, Richardson AM. Postmenopausal osteoporosis. JAMA. 1941;116:2465–74.

    Article  Google Scholar 

  50. Westerbeek ZW, Hepple RT, Zernicke RF. Effects of aging and caloric restriction on bone structure and mechanical properties. J Gerontol A Biol Sci Med Sci. 2008;63:1131–6.

    Article  PubMed  Google Scholar 

  51. Nagaraja S, Lin AS, Guldberg RE. Age-related changes in trabecular bone microdamage initiation. Bone. 2007;40:973–80.

    Article  PubMed  Google Scholar 

  52. Tommasini SM, Nasser P, Jepsen KJ. Sexual dimorphism affects tibia size and shape but not tissue-level mechanical properties. Bone. 2007;40:498–505.

    Article  PubMed  Google Scholar 

  53. Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res. 1987;(215):260–71.

    Google Scholar 

  54. Lee CC, Fletcher MD, Tarantal AF. Effect of age on the frequency, cell cycle, and lineage maturation of rhesus monkey (Macaca mulatta) CD34+ and hematopoietic progenitor cells. Pediatr Res. 2005;8:315–22.

    Article  Google Scholar 

  55. Szulc P, Seeman E. Thinking inside and outside the envelopes of bone: dedicated to PDD. Osteoporos Int. 2009;20:1281–8.

    Article  CAS  PubMed  Google Scholar 

  56. Rochefort GY, Pallu S, Benhamou CL. Osteocyte: the unrecognized side of bone tissue. Osteoporos Int. 2010;21(9):1457–69.

    Article  CAS  PubMed  Google Scholar 

  57. Banse X, Devogelaer JP, Lafosse A, Sims TJ, Grynpas M, Bailey AJ. Cross-link profile of bone collagen correlates with structural organization of trabeculae. Bone. 2002;31:70–6.

    Article  CAS  PubMed  Google Scholar 

  58. Viguet-Carrin S, Follet H, Gineyts E, Roux JP, Munoz F, Chapurlat R. Association between collagen cross-links and trabecular micro-architecture properties of human vertebral bone. Bone. 2010;46:342–7.

    Article  CAS  PubMed  Google Scholar 

  59. Currey JD. The relationship between the stiffness and the mineral content of bone. J Biomech. 1969;2:477–80.

    Article  CAS  PubMed  Google Scholar 

  60. Currey JD, Brear K, Zioupos P. The effects of ageing and changes in mineral content in degrading the toughness of human femora. J Biomech. 1996;29:257–62; erratum in J Biomech 30:1001, 1997.

    Article  CAS  PubMed  Google Scholar 

  61. LeGeros RZ. Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res. 2002;395:81–98.

    Article  Google Scholar 

  62. Loong CK, Rey C, Kuhn LT, Combes C, Wu Y, Chen S, et al. Evidence of hydroxyl-ion deficiency in bone apatites: an inelastic neutron-scattering study. Bone. 2000;26:599–602.

    Article  CAS  PubMed  Google Scholar 

  63. Rey C, Hina A, Tofighi A, Glimcher MJ. Maturational of poorly crystalline apatites – chemical and structural aspects in vivo and in vitro. Cells Mater. 1995;5:345–56.

    CAS  Google Scholar 

  64. Khosla S. Pathogeneiss of age-related bone loss. J Gerontol. 2013;68(10):1226–35.

    Article  CAS  Google Scholar 

  65. Hannon R, Blumsohn A, Naylor K, Eastell R. Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Miner Res. 1998;13:1124–33.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, NYU Long Island School of Medicine, NYU Langone Health, New York, NY, USA

    Henock T. Wolde-Semait

  2. Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, USA

    Daniel Komlos

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  1. Henock T. Wolde-Semait
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  2. Daniel Komlos
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Editor information

Editors and Affiliations

  1. Vice Chair and Residency Program Director, Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, USA

    Afshin E. Razi

  2. Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Stuart H. Hershman

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Wolde-Semait, H.T., Komlos, D. (2020). Normal Bone Physiology. In: Razi, A., Hershman, S. (eds) Vertebral Compression Fractures in Osteoporotic and Pathologic Bone. Springer, Cham. https://doi.org/10.1007/978-3-030-33861-9_1

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  • DOI: https://doi.org/10.1007/978-3-030-33861-9_1

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