Bone

Question 1

Trabecular v Cortical

Answer 1

• Trabecular - spongy/porous and metabolically active (20%)

- Cortical - very dense; not as metabolically active; provides shape and strength; esp in shafts of long bone (80%)

Question 2

Osteoblasts v Osteoclasts

Answer 2

• Osteoblasts - formation; lay down osteoid matrix then incorporated into matrix (osteocytes)
  
  • From mesenchymal stem cells
  • Fate: apoptosis, become osteocytes, line surface of bone
• Osteoclasts - resorption by secreting hydrogen ions and proteolytic enzymes that dissolve bone mineral and degrade matrix
  
  • Contain proton pumps that transport free Ca from bone surface –> into osteoclast –> circulation
  • From HSCs (like macrophages)

Question 3

Mineralization

Answer 3

• hydroxyapatite (Ca-phos) and Mg (stabilizes)
• Mineralization requires Ca and phosphate at same time (cannot mineralize w/ only Ca or only phosphate)
• Mineralization does not take place immediately after osteoid laid down
• Vit D for absorption of Ca and needed at site of bone formation for unknown reason
• Alkaline phosphatase - breaks down pyrophosphate –> ortophosphates which can be added to Ca

Question 4

2 Osteoclast Receptors

Answer 4

1- RANK ligand receptor

• PTH binds osteoblasts to activate them –> secrete RANK ligand –> RANK ligand binds receptor on osteoclast

2- OPC

• Osteoclasts can switch and express osteoprotegerin (OPC) instead of RANK ligand receptor then will not resorb bone (protective)

Question 5

Calcitonin

Answer 5

• From C cells
• Directly inhibits osteoclasts
• Those w/ medullary thyroid cancer and excess calcitonin maintain bone mass so does not have sig effect on regulation of bone turnover

Question 6

Which cytokines stiim bone turnover?

Answer 6

IL-1, IL-6, TNF-alpha

Question 7

Osteitis Fibrosa Cystica

Answer 7

• Mild/asymptomatic - high PTH –> inc resorption mainly from cortical bone; need surgery if presence of osteoporosis at any site
• Severe - could have pathological fractures or fibrotic cystic bone lesions; rare now
• Histo - inc # osteoclasts, osteoblasts and osteoid; may have fibroblasts in marrow space; microcysts
• Dx by serum Ca and PTH; meas bone density

Question 8

Rickets v. Osteomalacia (+ causes)

Answer 8

• Both are disorders of mineralization of newly made bone matrix from deficiency in Ca, phosphate or Vit D
• Rickets = kids; involves bones, growth plates and cartilage so can lead to bone deformities
• Osteomalacia = adults; just bones
• Poss Causes
  
  • Vit D def - diet, malabsorption, little sunlight
  • Chronic renal fail - less 1,25 Vit D
  • Defects in Vit D receptor gene - Vit D resistance
  • Rare disorders in phosphorous transport and alkaline phosphate –> dec phosphate
  • Aluminum (used to be used in water for dialysis)
  • Anti-convulsants can dec 25 Vit D if used chronically

Question 9

Classic Rickets Findings (4)

Answer 9

• Rachitic rosary (bumps on adjacent ribs @ costochondral junctions)
• Wide wrists and ankles (expansion of cartilage and plates)
• Bowing of long bones (softer from dec mineralization)
• Cupping of growth plates and cortical thinning on Xray

Question 10

Renal Osteodystrophy

Answer 10

• Collection of bone diseases associated w/ chronic end-stage kidney disease

1- High turnover form

- Dec 1, 25 Vit D synthesis and dec phosphate excretion/inc Ca excretion
- Ca also dec b/c binds to now excess phosphate (consumed)
- Low Ca --> high PTH levels --> inc turnover ("secondary hyperparathyroid")

2- Low turnover form

- Dec activity of osteoclasts/osteoblasts and dec osteoid formation
- Over-suppression of PTH from over-treatment w/ Ca and Vit D

3- Osteomalacia - see above (dec mineralization b/c less 1,25 Vit D and poss aluminum from dialysis)

Question 11

Osteogenesis Imperfecta

Answer 11

(“brittle bone disease”)

• Defect in type 1 collagen genes (COL1A1 and COL1A2); defects in collagen assembly and structural function
• Presentation - mult recurrent fractures, blue sclerae (thin so see scleral veins), mult fractures, ligament laxity, joint hypermobility, fragile and discolored teeth
• Clinical spectrum - from severe deformity/short stature to mild inc risk fracture

Question 12

Hypophosphatemia

Answer 12

• Genetic defects in alkaline phosphatase production; RARE
• Cannot treat like Rickets/osteomalacia
• Loss of function mutation in alk phos gene
• Clinical
  
  • Premature loss of teeth
  • Recurrent poor healing fracture
  • Resp insufficiency
• Tx - enzyme replacement; NOT Ca or Vit D replacement (can exacerbate symptoms)

Question 13

Paget’s Disease

Answer 13

• Focal, accelerated rate of bone remodeling resulting in bony overgrowth at single or multiple sites
• Usually in adults > 55 yo (juvenile form)
• Abnormal osteoclast appearance - inc # and multi-nucleated; then osteoblasts respond by inc their activity in intense and chaotic manner –> new bone w/ disorganized and mosaic appearance
• Inactivating mutation in TNFRSF11B gene encoding for OPG receptor on osteoclast is seen in some cases
• Clinical
  
  • Bone deformities (skull and hips); can lead to hearing loss if compress CN and headache
  • Warm skin over affected areas b/c inc blood flow
  • Bone pain
  • Elev serum alk phos
  • Arthritis and spinal stenosis
• Xrays - mixed osteolytic and sclerotic appearance of bone; thickening/enlargement of skull
• Bone scan - inc focal areas of uptake
• Tx - bisphosphonates