Structure & Composition of bone

Structure

  • specialized connective tissue
    • with minerals within infrastructure
  • organic compounds:
    • osteogenic cells
    • osteoblasts
    • osteocytes
    • osteoclasts
  • Tissue components of bone
    • Osteoid (major)
      • 30% of total skeleton mass
      • Made up of
        • Organic matrix
          • 90-95% of organic matrix : type 1 collagen fibers
        • Ground substance
          • ECF
          • glycoproteins
          • proteoglycans
            • chondroitin sulfate
            • hyaluronic acid
        • Osteocalcin
          • a vitamin K dependent protein
          • synthesized by osteoblasts at sites of new bone formation
          • binds to hydroxyapatite – participate in
    • Mineral matrix
      • Hydroxyapatite crystals
        • made up of bone salts (calcium & phosphate)
          • crystalline salts deposited in organic matrix
        • long, flat plate
        • Tightly packed around collagen
          • hardens bones
          • bones last longer after death
      • Other ions (conjugate to hydroxyapatite crystals)
        • Na+
        • Mg+
        • K+
        • CO3- (carbonate)

Bone cells (3 types)

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  • Osteoblasts
    • originate from progenitor cells within osteogenic tissue of the bone
      • arises from mesenchymal precursor cells in bone marrow
    • principal bone forming cell
    • while differentiating (to osteocytes)
      • acquire PTH & Vitamin D receptors
      • surface expression of alkaline phosphatase
      • expression of bone matrix protein genes
        • type 1 collagen
        • osteocalcin
        • osteopontin
        • others
    • Stimulate osteoclast formation and activation
      • via cell surface molecule RANKL
      • Receptor Activator Nuclear factor Kappa B ligand
      • stimulated by
        • Vit D
        • PTH
        • cytokines
          • IL-1
          • IL-6
          • IL-11
        • TNF
  • Osteocytes
    • originate from progenitor cells (same as above)
    • mature bone cells
      • derived from osteoblasts
    • occupies lacunae
    • remain trapped within the cortical bone during remodelling process
    • develops multiple processes – canaliculi
      • reach out through lacunae in bone tissue
      • communicate with
        • nutrient capillaries
        • processes of other osteocytes within unit of bone (osteon)
        • processes of surface osteoblasts
    • acts as cellular syncytium
      • permits translocation of minerals in and out of regions of bone removed from surfaces
    • sensors of mechanical loading
    • provide key signals
      • that trigger bone modelling and remodelling
    • responsible for osteocytic osteolysis (see below)
  • Osteoclasts
    • orginate from mononuclear phagocytic cells (haemopoietic monocyte lineage)
      • it is a multinucleated giant cell
      • from fusion of several precursor cells
      • bone resorption
        • during growth and skeletal remodelling
        • occupies the surface of bone and erode it
        • lies in Howship’s lacunae
          • dig a cavity into bone
          • at the site of contact with bone, there is a highly folded border – Ruffled border of microvilli

 

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  • Bone mineral
    • major form
      • hydroxyapatite crystals of varying maturity
    • minor form
      • amorphous calcium phosphate
        • occurs in regions of active bone formation
        • larger quantity in young bone
        • lacks a coherent x-ray diffraction pattern

Bone mineralization

  • Hydroxyapatite crystals are deposited on the collagen layers to produce lamellar bone
  • Mineralization requires (secreted in large amounts by osteoblasts)
    • ECF calcium
    • phosphate
    • alkaline phosphatase

Osteocytic osteolysis

  • Canaliculi of osteocytes permits exchange of calcium from the interior of bones to exterior
    • to ECF/Blood
    • or from exterior to bone
    • via breakdown of bone
  • Remove calcium from mineral crystals (bone, hydroxyapatite) when plasma Ca2+ level falls

Bone Calcification

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  • Osteoblasts secrete
    • collagen molecules (collagen monomers)
      • wire mesh
    • proteoglycans (ground substance)
      • cement
  • Collagen monomers polymerize to form collagen fibers
    • mix with ground susbstance
      • forming osteoid
      • cartilage like material
  • Calcium salts deposited in osteoid
  • Osteoblasts entrapped in osteoid
    • forming osteocyte
  • Calcium salts precipitate on the surface of collagen fibers
    • Form hydroxyapatite crystals
    • Why is hydroxyapatite not formed in normal tissues?
      • Calcium & phosphate in plasma is greater than those required to precipitate
      • Inhibitors present in all tissues
        • Pyrophosphate is inihibiting precipitation of hydroxyapatite in normal tissue
        • If pyrophosphate absent, will have precipitation of calcium in non osseous tissue
          • in arteriosclerosis
          • in old blood clot
        • In bone, osteoblasts secrete substances to inhibit pyrophospahte

Bone remodelling

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  • Bone resorption & bone deposit
    • at the surface of periosteum & endosteum
    • large volumes of bones are removed and replaced
      • continuous process
      • completion of full remodelling cycle lasts 6 months
      • except for growing bones, rate of deposition = absorption
  • Does not absolutely require hormones
    • but influences remodelling – like PTH
  • Bone remodelling unit/ Basic molecular unit (BMU)
    • osteoblasts
    • osteoclasts
    • macrophages
  • Bone remodelling process initiated by osteoclasts
  • Bone resorption
    • by osteoclasts
      • forms an adhesive ring – seals off an area
      • develops an elaborately invaginated plasma membrane structure – Ruffled border
        • Ruffled border villi secretes:
          • Citirc acid & lactic acid
            • from mitochondria & secretory vesicles
            • dissolves bone mineral/salts
          • Proteolytic enzyme/proteases (cathepsin K)
            • breaks down bone matrix
        • products endocytosed by osteoclasts and released into the interstitial fluid/blood
          • bone matrix
          • crystals
    • releases IGF-1 from bone matrix
      • stimulates osteoblast proliferation and differentiation
    • after osteoclasts done the resorption
      • macrophages phagocytose debris of old bone
      • clears the site before bone formation takes place
  • Bone formation
    • to increase bone strength and to repair injured bone
    • new bone deposits by osteocytes
    • Factors involved
      • local concentration of calcium & phosphate
        • regulated by
          • PTH
          • Vit D
            • helps to maintain intestinal absorption of minerals and ensure adequate supply of calcium & phosphorus
          • Calcitonin
      • matrix proteins
      • alkaline phosphatase
    • goes to site of resorption when osteoclasts release IGF-1 from bone matrix

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Regulation of bone remodelling

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Regulation of bone remodelling

  • Calcium homeostasis in blood (by hormones)
    • Parathyroid hormone (PTH)
      • both resorption and formation
      • increases proliferation of osteoclasts
      • activates already existing osteoclasts
      • increases bone resorption
        • hyperparathyroidism
          • increased osteoclastic activity
          • xray – extensive decalcification
          • multiple fractures of the weakened bones from slights trauma
      • PTH receptors in osteoblasts only. Osteoclasts have none.
    • Active form of vitamin D (DHCC)
      • promotes bone calcification
      • increased absorption of calcium & phosphate from the intestines
      • enhanced mineralization of bone
      • promote development of osteoclasts from precursor cells (act on bone cells)
      • vitamin D receptors in both osteoblasts and osteoclasts
    • Calcitonin
      • inhibits osteoclastic activity
      • decreases formation of new osteoclasts
      • inhibits bone resorption
      • increases bone deposition
    • Oestrogen
      • slow bone resorption
      • decreases the formation of osteoclasts
        • oestrogen deficiency (menopause)
          • activation of new bone remodelling sites
          • exagge
            ration of imbalance between bone formation and resorption
          • increases osteoclast recruitment and activity
          • increases apoptosis of osteoblasts
          • increases remodeling at trabecular bone (vertebral fractures common)
  • Mechanical & gravitational forces acting on the skeleton
  • By RANKL – ligand

NETT EFFECT

  • Bone resorption
    • PTH
      • osteoblast also secretes IL-6 – more resorption
      • inhibits collagen synthesis by osteoblasts
    • DHCC
      • both PTH & DHCC stimulate osteoblasts to secrete [M-CSF] & RANKL that causes osteoclast precursor cell proliferation
      • then differentiate into osteoclasts
      • fuse to form multinucleated osteoclasts
  • Bone formation
    • oestrogen
      • slows down resorption
  • Inhibit bone resorption
    • Calcitonin

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  • Osteoclast activation
    • RANKL + RANK
  • Osteoclast inhibition
    • RANKL + OPG

Osteon (Haversian system)

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Elongated tube of bone matrix with concentrically arranged lamellae of bone surrounding a canal containing blood vessels, nerves and lymphatic. The canal is lined by endosteum.

Haversian canals via Volksmann’s canal, communicates with:

  • one another
  • periosteum
  • marrow cavity

Volkmann’s canal:

  • no lamellae around it
  • lined by endosteum

Arrangement of collagen fibers – gives extra strength (withstand torsion stress)

  • In a particular lamellae
    • parallel and run in one direction
  • In adjaacent lamellae
    • run in opposite direction

Ossification/Osteogenesis

Refer foundation 1 notes

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Endochondral ossification

Starting from foetal skeleton, if it consist of:

  • Fibrous membranes
    • undergo Intramembranous ossification
    • skull cap and clavicle
      • fibrous connective tissue membrane have messenchymal cells
      • differentiate into osteoblast forming ossification center
        • secretes osteoid
        • forming non-calcified bone
      • blood vessels grow into osteoid
        • osteoblasts become osteocytes
        • osteoid calcified
      • covering messenchyme vascularize and form periosteum
      • external compact bone formed
      • internal spongy bone formed
  • Hyaline cartilage
    • undergo Endochondral ossification
    • All bones except skull cap and clavicle
      • bone collar formation
      • cartillage calcified
        • then destroyed
      • periosteal bud invades (blood vessel)
        • osteoblasts reach the center
        • via the blood vessels
      • osteoid formed
      • medullary cavity formed
      • osteoid calcified
    • primary center – diaphysis
    • secondary center – epiphysis

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Bone growth

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  • Growth in length (at adulthood, cartillage cell growth stops and epiphyseal plate becomes thinner & disappear)
    • Growth zone
      • cartilage cells multiply (mitosis)
    • Transformation zone
      • cartilage cells enlarge
      • matrix calcified
      • cartilage cells die
    • Osteogenic zone
      • osteoblasts secrete osteoid
      • osteoclasts remove the calcified cartilage
  • Growth in width
    • periosteal osteoblasts form new bone on the surface
      • increases width
    • endosteal osteoclasts remove bone from within
      • maintains marrow cavity

Bone repair

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  • Blood clot forms (hematoma)
    • bone cells die
    • dead tissue removed
  • Fibroblasts invade
    • collagen and cartilage formed (soft callus)
  • Osteoblasts invade
  • Cartilage removed
    • replaced by bone (bondy callus)
  • Excess bone is removed
    • Bone is remodelled

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