Bone Morphogenesis
The first and weaker type of bone formed. Also seen in adults after injury.
Woven bone
What type of collagen is found in bones, skin, cornea, and internal organs?
Type I collagen
What is the difference between Osteoporosis and Osteopetrosis?
Osteoporosis= loss of trabecular and cortical bone mass despite normal bone mineralization and Ca2+/PO43+ levels. Commonly caused by increased bone resorption b/c of dec estrogen levels and old age.
Osteopetrosis= failure of bone resorption due to defective osteoclasts. Leads to thick, dense bones that are prone to fracture
Why is OI sometimes confused with child abuse?
Multiple, recurrent fractures and bone deformities commonly happen after minimal trauma
What is a closed fracture vs open fracture?
Open= skin over/near fracture is lacerated by the injury
Closed= intact skin over/near the fracture
What bones are formed by membranous ossification? Endochondral ossification?
Membranous- flat bones (skull, facial bones, clavical)
Endochondral- axial + appendicular skeleton, base of skull
What is the basic unit of collagen? What is it made up of?
Basic unit= triple helix
Made up of 3 alpha chains
What conditions are caused by vitamin D deficiency?
Rickets/Osteomalacia
What is the range of severity for the types of OI (from most --> least severe), and what are their respective prognoses?
Type II, III, IV, I
Prognosis:
type I --> normal life expectancy, no long-bone deformity
types III-IV --> increased risk of premature death in both childhood + adulthood
type II --> lethal in utero
What is reduction of a fractured bone?
setting a broken bone. Putting it back into place to allow the bone to grow back together
What is the name of the crystalline structure found in bone matrix that houses calcium and phosphorus?
Hydroxyapatite Ca10(PO4)6(OH)2
What type of collagen is defectively produced in Osteogenesis imperfecta?
Type I collagen
What type of ossification is defective in achondroplasia?
Endochondral ossification is defective. Membranous ossification is not affected, leading to a large head relative to limbs (common cause of short-limbed dwarfism)
What are common symptoms of OI?
Multiple, recurrent fractures after minimal trauma
Blue Sclera (b/c of translucent connective tissue over choroidal veins)
Conductive Hearing loss (abnormal ossicles)
Dentinogenesis imperfecta (discolored/translucent teeth that are weak and easily break/ fall out)
How does growth plate involvement impact a bone fracture?
Growth plate involvement will affect how the bone will grow, so they require immediate treatment. If improperly treated, growth plate fracture can result in the affected bone ending up crooked or shorter than the other limb. Properly treated growth plate fractures usually heal without complications.
How does RANKL, OPG, and MCSF impact osteoclast activity?
More MCSF/RANKL --> more osteoclast activity
More OPG --> less osteoclast activity
What type of collagen is abnormal in some forms of Ehlers-Danlos Syndrome?
Type III
What are the phases of Paget's Disease?
1) osteolytic (osteoclasts break down bone)
2) mixed (osteoclasts + osteoblasts)
3) osteosclerotic (osteoblasts form bones, thick abnormal bone at focal spots, hypervascularity of bone)
4) quiescent (minimal osteoblast/osteoclast activity)
How is OI diagnosed?
Clinical Symptoms, family history, extraskeletal manifestations
No definitive lab test for OI, but sequence analysis of cDNA or genomic DNA testing of WBCs for mutations in COL1A1/COL1A2 can detect ~90% of type 1 collagen mutations. Negative genetic testing does not exclude diagnosis of OI.
Structure/quantity of type 1 collagen can be analyzed from fibroblast culture using a skin biopsy.
What is a displaced fracture? Bayonetted? Distracted?
displaced= the fragments are not in their usual anatomic alignment
bayonetted= the distal fragment longitudinally overlaps the proximal fragment
distracted= the distal fragment is separated from the proximal fragment by a gap
Describe endochondral ossification
Hyaline cartilage is secreted by chondroblasts and chondrocytes --> forms cartilage mold (anlagen) --> anlagen is converted to bone (osteoblasts lay down matrix from diaphysis --> epiphysis and epiphysis --> diaphysis at same time) --> anlagen is trapped and forms epiphyseal growth plate
Name the fibrillar collagens
Types I, II, and III
Fibrillar collagen= collagen molecules that assemble into polymers (fibrils)
What disease is caused by a mutation in COL1A1/COL1A2 genes?
What disease is caused by a mutation in COL5A1/COL5A2 genes?
COL1A1/COL1A2 --> Osteogenesis imperfecta
COL5A1/COL5A2 --> Ehlers-Danlos Syndrome
What are mainstays of treatment of OI?
Bisphosphonate therapy (pyrophosphate analog that is a potent inhibitor of bone resorption/turnover
Orthopedic surgery (fracture management, correction of bone deformities)
PT/OT (develop physical activity program that minimizes fracture risk while avoiding immobility; address impairments in ADLs
What are some methods of pain management commonly used when treating bone fractures?
Fracture immobilization (splinting), ice, elevation of affected limb, analgesics (minor- NSAIDs; severe-opioids)