Collagen and bone

Question 1

What is osteogenesis imperfecta?

Answer 1

• A hereditary condition resulting from a DECREASE in the AMOUNT of Normal TYPE 1 COLLAGEN due to
• 1) DECREASE COLLAGEN SECRETION
• 2) PRODUCTION of ABNORMAL COLLAGEN
• leads to ** INSUFFICIENT OSTEOID PRODUCTION :(**
  
  • ​Physeal osteoblasts can’t form sufficent osteoid
  • Periosteal osteoblasts can’t form sufficient osteoid so CAN’T remodell normally

​​** nb type 1 and “I” in Imperfecta **

Question 2

What is the genetics of osteogenesis imperfecta?

Answer 2

• 90 % have gene mutation
• COL 1A1 and COL 1A2
• causes-> ABNORMAL collagen x linkage via a Glycine subsitution in the PROCOLLAGEN molecule
• Both Autosomal dominant and Autosomal Recessive
• can be severe or mild (tarda form)

Question 3

What are the orhtopaedic manifestations of osteogenesis imperfecta ?

Answer 3

• Bone fragility and fracture
  
  • Heal in normal fashion intially but does not remodel
  • -Can lead to Progressive bowing
• Ligamentous laxity
• Short stature
• Scoliosis
• Codfish vertebra- compression fractures
• Basilar invagination( protrusion of the Odontoid process into the foramen magnum)-> apnea altered consciousness, ataxia
• Olecranon apophyseal avulsion fractions

Question 4

What other non-orthopaedic clinical manifestation occur ?

Answer 4

• Blue sclera
• Hearing loss
• Brownish opalescent teeth- dentinogenesis imperfecta
• Wormanian skull bones- puzzle piece intrasutural skull bones
• Increased risks of malignant hyperthermia

Question 5

What is the classification for osteogenesis imperfecta?

Answer 5

Originally by SILLENCE

• 4 Types but more added since
• Type 1
  
  • AUTOSOMAL DOMINANT
  • ​Blue sclera
  • mildest form
  • presents at preschool age (tarda)
  • Hearing effected 50%
  • Divided into A or B if teeth involved
• Type 2
  
  • ​AUTOSOMAL RECESSIVE
  • Blue sclera
  • LETHAL :( in perinatal period
• Type3
  
  • ​Autosomal recessive
  • NORMAL SCLERA
  • fractures at birth
  • Progressively Short sature
  • Most severe survival form
• Type 4
  
  • ​Autosomal dominant
  • NORMAL SCLERA
  • Moderate severity
  • Bowing bones and vertebral fractures common
  • Hearing normal
  • Divided A or B on teeth​
• Type 5-7 added later, these have no type 1 collagen mutation but ABNORMAL BONE on microscopy

Question 6

What are the symptoms of osteogenesis imperfecta?

Answer 6

Mild cases

• Multiple fractures during childhood

Severe

• Fractures Present at birth - can be fatal
• No of fractures typically decreases as pt ages adn ussually stops after puberty

Basilar invagination

• presents with apnea,altered consciousness, ataxia and myelopathy
• usually in 3-4th decade of life, but can be as early as teenagers

Question 7

What are the signs of osteogenesis imperfecta?

Answer 7

• Multiple fractures leads to
• saber shin - appearamce of tibia
• Bowing of long bones

Question 8

What are the radiological findings?

Answer 8

• Thin cortices
• Generalised osteopenia
• Saber shins
• Skull radiographs reveal WORMIAN bones

Question 9

What is found on histology ?

Answer 9

• Increased HAVERSIAN canals and osteocytes lacunae
• Increased no of osteoblasts and osteoclasts
• Decrease no of trabeculae
• Decreased a cortical thickness
• Replicated cement lines

Question 10

What is diagnosis based on in osteogenesis imperfecta?

Answer 10

• Clinician findings, typical radiographs and fhx
• There is no commercial test due to variety of gene mutations

Question 11

How would you tx a pt with osteogenesis imperfecta with a fracture ?

Answer 11

Non op

• Observation.
  
  • if Child <2yrs tx as child without OI

Surgery

• Fixation with telescoping rodes
  
  • if pt >2 years
  • allow continued growth

Question 12

What could be done to prevent fractures in osteogenesis imperfecta?

Answer 12

• Bracing
  
  • to decrease deformity and lessen fractures
• BISPHOSPHONATES
  
  • indicate in most Osteogensis imperfecta to reduce Fractures
  • Function is to increase cortical thickness by inhibiting osteoclasts- chronic use = metaphyseal bands on X-ray
• Growth hormone
• Bone marrow transplantation
  
  • used with some succes

Question 13

How are long bone bowing deformities tx?

Answer 13

Operative

• Realignment OSTEOTOMY With rod fixation
  
  • in severe deformity to reduce fracture rates
  • Telescopic rod= Sheffield rod ,
  • Non telescopic= Williams’s rods, rush rods

Question 14

When and how would you tx scoliosis in a pt with Osteogensis imperfecta ?

Answer 14

• If curve > 45 degrees Bracing is ineffective

Operative

• POSTERIOR SPINAL FUSION for curves **> 45^o **in mild form or >35^o degrees in severe
• Technique is a challenge due to porosity of bone
• Use allograft instead of iliac autograft due to paucity of bone
• Anterior spinal fusion only indicated in very young children to prevent crankshaft
• Assoc with LARGE Blood LOSS

Question 15

How is basilar invagination tx?

Answer 15

Operative

• decompression and posterior fusion
• radiographic changes of invagination with cord compression with physical exam findings of myelopathy

Question 16

What is osteopetrosis?

Answer 16

• A metabolic bone disease caused by defective osteoclastic resorption of immature bone

Question 17

What is the pathophysiology of Osteopetrosis?

Answer 17

• Inability to cause acidification in the clear zone and therefore prevent bone resorption
• leads to dense bone and obliterated medullary canal
• may be linked to defect in thymus

Question 18

What are the forms of osteopetrosis?

Answer 18

• Autosomal recessive
  
  • lethal
  • death in infancy
  • mapped chromosome 11q13
• Autosomal Dominant
  
  • compatible w life but assoc w morbidity
  • mutations causing deactivation in 3 genes
  • carbonic anhydrase 2
    
    • normally an ​enzyme that converts carbon dioxide and water into H+ and bicarbonate. The protons created are then transported across the ruffled border of osteoclasts, leading to acidification and demineralization of bone matrix
  • alpha 3 subunit of vacuolar proton pump
  • chloride channel 7

Question 19

what are the signs and symptoms of autosomal recessive osteopetrosis ?

Answer 19

Symptoms

• Frequent fractures
• progressive blindness and deafness
• Severe anaemia - encroachment of bone into bone marrow starts in early infancy

Signs

• Macrocephaly
• hepatosplenomegaly
  
  • caused by compensatory extramedullary haemopoiesis
• Dental abscess & osteomyelitis of mandible

Question 20

what are the signs anf symptoms of autosomal dominant osteopetrosis?

Answer 20

• Not discovered until adulthood
• may present w pathological fx
• anaemia ( fatigue)

Signs

• Generalized osteosclerosis
• cranial n palsy

Question 21

What is seen on radiographs with osteopetrosis?

Answer 21

• Erlenmeyer flask proximal humerus and distal femur
• rugger jersey spine w very dense bone
• loss of medullary canal ‘ bone within bone appearance’
• block femoral metaphysis- see pic

Question 22

What is seen in the histology of osteopetrosis?

Answer 22

• Defective osteoclasts
• osteoclasts lack ruffled border and clear zone
• islands of calcified cartilage with mature trabeculae

Question 23

What is the tx of osteopetrosis?

Answer 23

• Non operative
  
  • High dose Calcitrol ( 1-25 dihydroxy vitamin D)
  • Bone marrow transplant
    
    • for AR form
  • Interferon Gamma-1beta
    
    • autosomal dominant form

Question 24

What is Ehlers-Danlos syndrome?

Answer 24

• Connective tissue disorder characterised by
  
  • hyperelasticity/fragile skin
  • joint hypermobility and dislocation
  • generalised ligamentous laxity
  • poor wound healing
  • early onset arthritis
  • soft tissue
  • Soft tissue & bone fragility
  • mitral valve collapse- aortic root dilation
  • DDH
  • clubfoot
  • pes planus
  • scoliosis
  • high palate

Question 25

What are the genetics of ehlers - danlos syndrome?

Answer 25

* **COL5A1 or COL5A2 mutation in 40-50%** * **gene for type V collagen** * important in proper assembly of skin matrix collagen fibrils & basment membrane

Question 26

Name the classification of ehler's danlos syndrome?

Answer 26

* Berlin classification- revised * types 1-X1 * types 2 and 3 most common and least disabling

Question 27

What are the signs and symptoms of ehler's danlos syndrome?

Answer 27

Symptoms * Double jointed * easily damaged bruised/stretchy skin * easy scarring & poor wound healing * increaed joint mobility, joint popping, early arthritis * esp shoulders, patellae, ankles * **Chronic musculoskeletal pain- 50%** _​Signs_ * a score of 5 or more on 9 point **Beighton-Horan** scale = hypermobility * hyperextension little finger past 90o = 1 point each * passive abduction of each thumb to foream= i point each * hypertension of knee = 1 point each * hyperextension of elbow= 1 point each * forwarad flexion of trunk w palms flat on floor w knees extended = 1 point

Question 28

What is seen on radiographs of Ehlers danlos syndrome?

Answer 28

* Look for **subluxations/dislocations** * kyphoscoliosis

Question 29

How is Ehlers Danlos syndrome diagnosed?

Answer 29

* Collagen typing of skin biopsy

Question 30

What is the tx of ehler's danlos syndrome?

Answer 30

_Non operative_ * PT/Orthotics and supportive measures for pain * mainstay of tx _Surgery_ * **Arthrodesis** * ​joint recalcitrant to non op mx * soft tissue procedure are likely unsuccessful in hypermobile joints * **Posterior spinal fusion** * progressive scoliosis ( most common in kyphoscoliosis type) * Longer fusions needed to prevent junctional problems