Bone

Question 1

Bone Matrix (Osteoid)

Answer 1

• Collagen Type I
• Ground substance -
  
  • LOW proteoglycan conc (unlike cartilage)
  • Glycoproteins
    
    • 1- Osteonectin- LINKER; links collagen and osteocytes to matrix
    • 2- Osteocalcin - binds Ca++ for mineralization
    • 3- Osteopontin - creates seal during turnover by binding osteoclast integrins
• Minerals - Ca ++ and phosphate = hydroxyapetite (forms long crystals that bind to collagen I)
• Water - less than cartilage

Question 2

Periosteum

Endostium

Answer 2

• Periosteum - has 2 layers just like perichondrium (fibrous layer and osteogenic layer for appositional growth)
• Endosteum - inner layer; also contains osteoprogenitor cells so also capable of appositional growth

Question 3

Compact v Spongy Bone

Answer 3

• Compact Bone - form Haversian systems w/ canaliculi for blood/nutrients; lower rate of turnover
• Spongy Bone - (AKA cancellous or trabecular)
  • Made of thin plates or trabeculae that disperse and support weight (esp at edges of long bone)
  • NO Haversian systems so all osteocytes must be w/in .1 mm of blood vessels and have canaliculi
  • Higher rate of turnover

Question 4

Haversian Systems (5 components)

Answer 4

• Haversian canal in center - contains blood vessels and nerves- lined w/ endosteal/stem cells
• Lamellae- rings of collagen, mineralized matrix and osteocytes in lacunae in concentric circles around canal
• Obtain nutrients via canaliculi
• Volkmann’s Canal - perpendicular to Haversian canals; allow vasculature to travel between canals
• Cement Lines- connective tissue anchors b/n adjacent Hav systems

Question 5

Osteoclast Function

Answer 5

• Cells that digest matrix (bone resorption) via acid and enzyme release
• Steps:
  • 1- Complex of actin, integrins and osteopontin create seal to keep acids and enzymes w/in
  • 2- ATP-dep proton pump –> H+ out of cell
  • 3- less H+ in cell causes carbonic anhydrase II to favor production of H+ and bicarb
  • 4- Bicarb pumped out and Cl- pumped in via bicarb-chloride exchanger
  • 5- Cl- exits cells passively via Cl- channels
  • 6- lysosomal enzymes and MMPs released via vesicles

-Growth, remodeling, repair

Question 6

Intramembraneous Ossification

Answer 6

• (de novo) - start w/ mesenchymal cells —> differentiate into osteoblasts which secrete matrix and then trap themselves w/in it (osteocytes) as it is mineralized
• Initiated/influenced by BMPs (bone morphogentic proteins)

Question 7

5 Stages of Endochondrial Ossification

Answer 7

• Zone of Resting Cartilage (chondrocytes not mitotic - reserve)
• Zone of Proliferating Cartilage (chondrocytes rapidly dividing - isogenous groups- responsible for growth in length)
• Zone of Hypertrophied Cartilage (individual cartilage cells get larger and start to express Vit D rec —> collagen X, alkaline phosphatase, chondrocalcin, collegians and vascular endothelial growth factor —> hydroxyapetite precipitate)
• Zone of Calcified Cartilage (chondrocytes die b/c mineralization blocks nutrients)
• Zone of Resorption and Ossification (angiogenesis, osteoblasts make matrix and osteoclast remodeling)

Question 8

Primary Bone –> Secondary Bone

Answer 8

• done via osteoclasts (Remodeling)
  
  • Resorb primary woven bone from the Zone of Ossification
  • 3 Options…
    
    • Create open marrow cavity
    • Create compact bone
    • Create spongy bone
  • Osteoclasts digest a “cutting cone” into dense bone tissue THEN rebuild new Havarian systems from outside in (compact bone) OR remodel trabecular (spongy bone)
  • Turnover occurs throughout life (turnover rate of spongy&raquo_space;>compact)

Question 9

Bisphosphates for Osteoporosis

Answer 9

• shut down vesicular transport which prevents osteoclast function BUT specific b/c incorporated into bone matrix
• Drawback = slight inc risk of spontaneous fracture or osteonecrosis

Question 10

Raloxifene for Osteoporosis

Answer 10

• SERM
• estrogen agonist in bone which dec osteoclast differentiation
• Drawback = slight inc in clot formation

Question 11

Calcitonin for Osteoporosis

Answer 11

• synthetic salmon calcitonin which has greater affinity than human calcintonin —> apoptosis of osteoclasts

Question 12

Prolia/Denosmab for Osteoporosis

Answer 12

• antibody against RANK ligand prevents ligand from binding RANK so osteoclast precursors do not mature
• Drawback = RANK also involved in immune cells so can inc infections

Question 13

Cathepsin K Inhibitors for Osteoporosis

Answer 13

• inhibit osteoclast enzyme

- Drawback = taken off market b/c inc risk of a fib

Question 14

Teriparatide (PTH 1-34) for Osteoporosis

Answer 14

• specific wedge of PTH has diff effect when binding PTH receptor —> osteoblast activation via cAMP path
• Drawback = risk of osteosarcoma so only use for 1-2 yrs