• Clinical science

Bone tissue (Osseous tissue)

Abstract

The musculoskeletal system is comprised of bones and connective tissue structures, such as cartilage, ligaments, and tendons. These structures are brought into motion by skeletal muscles. To withstand resultant forces, bone tissue resists pressure and tension and is minimally elastic. Bone tissue mainly consists of bone cells (osteoblasts, osteocytes, and osteoclasts) and a mineralized extracellular matrix that is primarily made up of collagen fibrils and hydroxyapatite crystals. Ossification, or bone formation, begins with a framework that consists of either mesenchymal connective tissue (intramembranous ossification) or cartilage (endochondral ossification). Woven bone is formed, which is replaced by the more solid and layered lamellar bone. The outer cortical layers can be macroscopically differentiated from the branched center of the trabeculae.

Overview

Function of bone

  • Supportive function
  • Protective function
  • Storage (calcium and phosphorus reservoir)
  • Hematopoiesis

Types of bone

References:[1][2]

Bone composition

The exact composition or organization of individual bone components differs in the various bones types and maturation stages. All human bones are composed of the same basic elements:

Bone cells

Definition Function Location
Osteoprogenitor cells
  • Barely differentiated precursor bone cells that originate from the mesenchyme
Osteoblasts
Osteocytes
  • Osteoblasts on which a new osteoid layer has been deposited
Osteoclasts
  • Bone-dissolving multinucleated phagocytes that degrade mineralized bone and are formed via fusion of monocyte precursor


Bone matrix

Composed of organic and inorganic material

Bone membranes

The periosteum and the endosteum consist of the same type of bone cells!

Bone marrow

For more details on bone marrow, see the learning card on basics of hematology.

References:[3]

Development and maturation

Development of bone

Ossification

Endochondral ossification Membraneous ossification
Definition
Process
  1. Mesenchymal cells differentiate into osteoblasts at the ossification center.
  2. Osteoblasts deposit osteoids → osteocytes form after osteoid mineralization → formation of a bone segment
  3. The osteoblasts on the outer surface of the bone segment deposit osteoid layers → appositional growth
  4. Fusion of several bone segments to primary trabecular bone
  5. Blood vessels and undifferentiated mesenchymal cells invade the trabecular bone → formation of bone marrow
  6. Simultaneous construction and remodeling of bone (woven bonelamellar bone)
  7. Mesenchymal layers that do not become ossified → formation of endosteum and periosteum
Examples

The skull undergoes both processes: The viscerocranium (e.g., frontal bone) is derived from the neural crest and undergoes membranous ossification, whereas the chondrocranium (e.g., sphenoid, ethmoid bone) and neurocranium (e.g., occipital and parietal bones) are derived from paraxial mesoderm and undergo endochondral ossification!

Stages of bone maturity

Bones are arranged into woven bone (primary bone) during embryonic development or bone healing. The structure of woven bone is disorganized and transformed into organized tissue of lamellar bone (secondary bone) through continuous remodeling.

The direction of collagen fibers of the bone extracellular matrix is an important distinguishing characteristic between immature woven bone and mature lamellar bone!

Woven bone Lamellar bone
Definition
  • Immature bone that is formed during fetal development and bone healing
  • Mature bone formed by remodeling of woven bone
Histology
  • Disorganized collagen fibers
  • Less mineralized bone substance with a high water content
  • Rich in cells
Characteristics
  • Mechanically weaker and more flexible than lamellar bone
  • Mechanically strong
Remodeling
  • Usually remodeled successively after birth (and in secondary bone healing) to more stable lamellar bones
  • Load-dependent, continuous remodeling of bone according to acting forces

Vascularization of lamellar bones

The course of lamellar bone vessels is strictly defined by the Haversian and Volkmann's canal structures. In contrast, woven bone vessels are disorganized!

Development of long bones

  1. Primary ossification center: diaphysis
    1. Bone collar formation
    2. Enchondral ossification
  2. Secondary ossification center: epiphysis
  3. Longitudinal growth of the long bones

Epiphyseal plate

The part of the bone where longitudinal growth takes place. Layers include (from epiphysis to diaphysis):

  1. Zone of resting cartilage
  2. Proliferation zone: mitosis of chondrocytes
  3. Zone of hypertrophy
  4. Zone of calcification
    • Functions
    • Process
      • Secretion of VEGF and matrix metalloproteinases by chondrocytes
      • Blood vessels and macrophages migrate → transverse septa erode
    • Effect: mineralized columns remain (ossified longitudinal septa)
      • Approx. ⅓ of the longitudinal septa is retained with the remaining septa degraded by chondroclasts.
  5. Zone of ossification: colonization of the mineralized longitudinal septae by osteoblastsosteoid formation → mineralization

Achondroplasia is a genetic disorder with impaired cartilage formation and results in a short stature. It especially affects the epiphyseal plates of the long bones, which close prematurely. The absence of longitudinal growth leads to a short stature with a disproportional body stature (e.g., normal trunk with a disproportional head and short, plump extremities).
During childhood or adolescence, a fracture near a joint may damage the unclosed epiphyseal plate, which can result in growth disorders (e.g., asymmetry, inhibition, acceleration) during healing.

References:[4]

Bone remodeling and healing

The human skeleton is in a continuous dynamic state of remodeling. Not only does this apply to the replacement of immature woven bone by lamellar bone, but also for adaptation of adult bones to their individual load.

Bone remodeling

  • Cells involved: osteoclasts (degrade) and osteoblasts (build)
  • Duration: usually longer than the lifespan of cells involved → continual replacement of cells involved

Blasts build, clasts crumble!

Bone remodeling in cortical bone

Bone remodeling in trabecular bone

Regulation of bone remodeling

Estrogen has a positive effect on bone balance because it inhibits osteoclast formation and activation (i.e., RHL effect) and increases OPG formation!

Bone healing

Fractures occur when bones are strained beyond their maximum load. Fractures can heal in two different ways.



References:[5][6][7][8][9]

Clinical significance

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  • 2. Hill MA. Musculoskeletal System - Skull Development. https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Skull_Development. Updated May 9, 2018. Accessed June 28, 2018.
  • 3. Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004; 15(1): pp. 49–60. pmid: 14746813.
  • 4. Patton KT, Thibodeau GA. Anthony's Textbook of Anatomy & Physiology. Maryland Heights, MO: Mosby; 2014.
  • 5. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
  • 6. Hall JE. Guyton and Hall Textbook of Medical Physiology. Philadelphia, PA: Elsevier; 2016.
  • 7. Rucci N. Molecular biology of bone remodelling. Clin Cases Miner Bone Metab. 2008; 5(1): pp. 49–56. pmid: 22460846.
  • 8. Ross MH, Pawlina W. Histology. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
  • 9. Sela JJ, Bab IA. Principles of Bone Regeneration. Berlin, Germany: Springer Science & Business Media; 2012.
  • Blair HC, Larrouture QC, Li Y, et al. Osteoblast differentiation and bone matrix formation in vivo and in vitro. Tissue Engineering Part B: Reviews. 2017; 23(3): pp. 268–280. doi: 10.1089/ten.teb.2016.0454.
last updated 11/18/2018
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