Bone pathology

Introducing bone
The skeleton is composed of bone and cartilage. Importance of skeletal system 1. Mechanical support 2. Role in mineral homeostasis 3. Hematopoietic elements 4. Protection 5. Size and shape of body Bone is a type of connective tissue. Composed of 1. Inorganic and 2. Organic components.

Inorganic component
Calcium hydroxyapatite Gives bone strength and hardness. Store house for Ca, P, Na and Mg. Osteoid: is composed of type I collagen, which is mineralized to form compact bone by the deposition of calcium hydroxyapatite.

Organic Component
Cells of the bone 1.Osteoprogenitor cells 2.Osteoblasts Bone forming cells 3.Osteocytes 4.Osteoclasts Matrix proteins Type I collagen Osteocalcin Glycoproteins, proteoglycans etc.
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Cells of the bone

Osteoprogenitor cells: Are pluripotent mesenchymal stem cells. Produce osteoblasts. Osteoblasts: Responsible for production of osteoid Contain high amounts of alkaline phosphatase. Modulate osteoclast function. have receptors for PTH, vitamin D and estrogen.
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Clinical pearl
Elevated levels of serum alkaline phosphatase is marker of bone formation. Is elevated in all bone diseases that result in increased bone turnover.

Osteoblasts Osteoid

Osteoblasts synthesizing bone matrix

 Osteocytes: Are osteoblasts that have become surrounded by matrix. Communicate with each other and surface cells via canaliculi (network of tunnels) help to regulate , Ca levels and remodeling of the skeleton..

Osteoclast
Multinucleated giant cells (6-12 nuclei) Responsible for bone resorption. Derived from same cell as monocytes and macrophages. Contain high amounts of acid phosphatase and collagenase. Resorb bone within Howships lacunae

Osteoblasts

Osteocytes Osteoclast

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Osteoclasts

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Osteoclastogenesis

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Osteoclastogenesis
Factors that play a role in osteoclast development IL-1**, IL-6, IL-3 , IL-11, M-CSF** etc. These act on osteoblasts and stromal cells. Modulate the activity of: 1. RANK = Receptor Activator for Nuclear factor kB 2. RANK ligand = RANKL 3. Osteoprotegerin (OPG)
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1. RANK (Receptor Activator of Nuclear Factor kB): Present on precursors of osteoclasts. 2. RANK ligand (RANK-L): Present on osteoblasts. Binding of RANK to RANKL stimulates development of osteoclasts. 3. Osteoprotegerin (OPG): Secreted by osteoblasts Acts as a decoy receptor. Binds to RANKL & Blocks its action inhibiting osteoclastogenesis. 14

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Osteoprotegerin

RANK ligand M-CSF

RANK

Osteoclast precursor

M-CSF receptor

Osteoclast
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Osteoclastogenesis depends on the balance between RANK-L and OPG. Prostaglandins and parathyroid hormone: increase RANK-L decrease OPG, PROMOTE BONE RESORPTION. TGF-beta: diminishes RANK-L and enhances OPG expression, DECREASES OSTEOCLAST ACTIVITY. Estrogen: dampens M-CSF and stimulates OPG. DECREASES OSTEOCLASTOGENESIS.

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The proteins of bone

Type 1 collagen : produced by osteoblasts. Woven bone: Collagen deposited in a random weave seen in fetal skeleton produced quickly and resists forces equally from all directions presence of WB in adult indicates a pathologic state Lamellar bone: Collagen deposition in an orderly layered manner. 18 Stronger

Woven bone

Lamellar bone

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Formation of bone
Intramembranous bone: Direct bone formation without a cartilage model. Flat bones such as the cranial bones, clavicles, vertebrae, ankle bones. Enchondral bone: Indirect bone formation from a cartilage model. Bone is formed from cartilage at the epiphyseal growth plates. Long bones such as femur, humerus, tibia etc.
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Bone modeling and remodeling

Occurs throughout life Is necessary to maintain healthy bones Bone resorption by osteoclast balanced with bone formation by osteoblast.

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Cartilage
Cartilage is mainly composed of collagen. It is derived from chondroblasts that give rise to chondrocytes. Types of cartilage: Hyaline cartilage: Present in the ends of the bones that form movable joint. Fibrocartilage: Connects bones that do not have a wide range of motion. Elastic cartilage: Provide great resilience for structures such as the external ear, the nose, and the epiglottis. 22

Parts of a long bone

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Cortical Bone

Cancellous bone

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Parts of bone
Grossly two types of bones: Cortical bone: dense, compact bone It composes 80% of the skeleton. Cancellous bone (also termed spongy, trabecular, or marrow bone): found at the ends of long bones within the medullary canal, vertebral bodies. All bones contain both cancellous and cortical elements.
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Disorders of bone
1. Neoplastic 2. Non-neoplastic

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