R/O - Pathology of bone disorders Flashcards
unmineralized bone is called:
osteoid
osteoblasts secrete what growth factors?
- IL-1
- RANKL (receptor activator of NFkB which combines with RANK receptor on osteoclasts
what cells live in howship lacunae?
osteoclasts
osteoclasts are derived from what lineage?
hematopoietic progenitor cells
what type of bone?
- normally present in fetal skeleton, growth plates, and processes where there is very rapid bone production
- almost always pathologic in adults
woven
what are the 4 types of lamellar bone?
- concentric
- interstitial
- inner circumferential
- outer circumferential
what are the 3 developmental disorders of bone pathology?
- achondroplasia
- osteogenesis imperfecta
- osteopetrosis
what is the pathology of achondroplasia?
- point mutation in gene encoding for FGFR3
- FGFR is persistently activated - inhibition of normal proliferation of chondrocytes at growth plates
what is the inheritance of achondroplasia?
AD
premature sealing of growth plates - diagnosis?
achondroplasia
what cell type is proliferating in the zone of proliferation?
chondrocytes
what is the pathology of osteogenesis imperfecta?
- abnormalities of type 1 collagen synthesis
- mutations in genes that code for a1 an a2 chains
what is the inheritance of osteogenesis imperfecta?
AD
what are the 4 main types of osteogenesis imperfecta?
- type I: increased fracture risk, not deforming
- type II: lethal, multiple fractures in utero
- type III / type IV: progressive deformity
what is the morphology seen in OI?
- decreased bone thickness because of sluggish periosteal bone formation
- reduced number of trabeculae
- abnormally thin trabeculae
osteopetrosis is due to defective activity of what cell type?
osteoclasts
what is the pathology of osteopetrosis?
- decreased osteoclastic bone resorption
- diffuse skeletal sclerosis
what is the inheritance of osteopetrosis?
- AR: malignant
- AD: benign (normal life span)
what is the clinical picture of osteopetrosis?
- increased incidence of fracture (more brittle)
- anemia
- thrombocytopenia
- increased susceptibility to infections (less marrow space)
- possible cranial nerve palsies
what parts of bone are thinned in osteroporosis?
cortex and trabeculae
what are the primary causes of osteoporosis?
- age
- menopause
what is the best imaging modality for osteoporosis? why?
DEXA - identifies quantitative loss of bone
how does estrogen increase bone formation?**
- increases collagen synthesis by osteoblasts
- prevents bone resporption by inhibiting osteoclast differentiation (osteoprotegerin)
how does decreased estrogen (menopause) lead to decreased bone density?**
regulation of osteoclast activity:
- increased secretion of IL-1, IL-6, TNF, leading to increased RANK which stimulates osteoclasts
- decreased levels of osteoprotegerin (OPG), which is protective of bone
how does glucocorticoid excess affect osteoclast metabolism?
increase in:
- osteoclast survival
- cancellous osteoclasts
- bone resorption
how does glucocorticoid excess affect osteocyte metabolism?
- increased apoptosis
- decreased canalicular circulation
- decreased bone quality
how does glucocorticoid excess affect osteoblast metabolism?
- decreased osteoblastogenesis
- increased apoptosis
- early and continual decrease in cancellous osteoblasts, synthetic ability, bone formation
- generalized pain
- fractures
- mottled areas of lucency (“pseudofractures”)
osteomalacia
- skeletal deformities
- loss of rigidity
- bowing of the legs
- enlarged costochondral junctions
- pigeon breast deformity
- kyphosis
- frontal bossing
rickets
osteomalacia is characterized by:
abnormally high ratio of osteoid to mineralized bone
