MSK 424 - 428 Flashcards
explain why estrogen is bone protective
estrogen blocks apoptosis in bone forming osteoblast and induces apoptosis in bone-resorbing osteoclast
what bone cell secretes acid and collagenases?
osteoclast
what cell is multinucleated and is derived from monocyte?
osteoclast
what bone path takes place in epiphysis?
Giant cell tumor
what bone paths take place in metaphysis?
osteosarcoma, osteochondroma
what bone paths take place in diaphysis?
Ewing sarcoma, myeloma, osteoid osteoma
which bone path is associated with nighttime pain, central nidus, and pain released by aspirin?
osteoid osteoma
3 characteristics of Ewing sarcoma?
- anaplastic small blue cell malignant tumor
- extremely aggressive with early metastases, but responsive to chemotherapy
- “onion skin” periosteal reaction in bone
what population is most affected by Ewing sarcoma?
boys
what is the 2nd most common primary malignant tumor after multiple myeloma?
osteosarcoma (osteogenic sarcoma)
name 5 predisposing factors for osteosarcoma (osteogenic sarcoma)
- paget dz of bone
- bone infarcts
- radiation
- familial retinoblastoma
- Li Fraumeni syndrome (germline p53 mutation)
what is the age distribution who get osteosarcoma?
biomodal distribution (10-20 yr old and more than 65)
what other malignancy has also bimodal distribution?
hodgkin (young adulthood and more than 55)
on x-ray, how will osteosarcoma look like?
codman triangle (from elevation of periosteum) or sunburst pattern on x-ray
what is the most common benign tumor?
osteochondroma
does osteochondroma transform to chondrosarcoma?
rarely yes
what is the characteristic of osteochondroma?
mature bone with cartilagionus (chondroid) cap
what bone tumor is characterized as soap bubble appearance on x-ray with multinucleated giant cells
giant cell tumor
what is the most common site of giant cell tumor?
epiphyseal end of long bone around knee
in paget dz of bone, hearing loss is due to
auditory foramen narrowing
name the 4 stages of paget dz of bone
- lytic (osteoclast)
- mixed (osteoclast + osteoblast)
- sclerotic (osteoblast)
- quiescent (minimal osteoclast/osteoblast)
explain the pathophysio of the paget dz of bone
common, localized disorder of bone remodeling cause by inc in both osteoblastic and osteoclastic activity
what bone path is associated with mosaic pattern of woven and lamellar bone?
paget dz of bone
what is the most common site of osteonecrosis (avascular necrosis) and why?
femoral head (due to insufficiency of medial circumflex femoral artery)
name 7 causes for osteonecrosis
ASEPTIC
- alcoholism
- sickle cell
- storage dz (Guacher)
- exogenous steroid
- pancreatic
- trauma
- idiopathic
- caisson (the bend)
what is another name for idiopathic cause of osteonecrosis?
Legg Calve Perthes dz
phosphorylation of myosin is done by what enzyme and will this lead to contraction or relaxation?
myosin light chain kinase, contraction
dephosphorylation of myosin is done by what enzyme and what will this lead to?
myosin light chain phosphatase, relaxation
inc Ca2+ calmodulin complex activates which enzyme?
myosin light chain kinase
bones of axial and appendicular skeleton and base of skull are considered as what type of bone formation?
endochondral ossification
what is membranous ossification?
bones of calvarium and facial bones
woven bone is formed directly without
cartilage
cartilaginous model of bone is first made by
chondrocytes
what is the pathophysio of achondroplasia?
(gain of function), constitutive activation of fibroblast growth factor receptor (FGFR3) inhibiting chondrocyte proliferation
mode of inheritance of achondroplasia?
autosomal dominant with full penetrance (homozygosity is lethal)
how is Laron syndrome diff from achondroplasia?
small genitalia, dec linear growth, everything small due to defective growth hormone receptor
treatment drugs for type 2 (senile) osteoporosis?
bisphosphonate, PTH analog (teriparatide), SERMs, calcitonin, denosumab
what is denosumab?
monoclonal antibody against RANKL
what bone path is associated with bone filling marrow space leading to pancytopenia and extramedullary hematopoiesis?
osteopetrosis (marble bone dz)
what is defective in osteopetrosis?
failure of normal bone resorption due to defective osteoclast leading to thickened, dense bones that are prone to fracture
what mutation is responsible for osteopetrosis?
mutations in carbonic anhydrase II impairing the ability of osteoclast to generate acidic environment necessary for bone resorption
what renal path will also have impaired carbonic anhydrase?
proximal (type2) urine pH
what is the treatment for osteopetrosis?
bone marrow transplant is curative as osteoclast is from monocytes
what path is associated with “bone-in-bone” appearance on x-ray?
osteopetrosis
what is the diff btw osteoporosis and osteomalacia in terms of bone mineralization?
normal bone mineralization in osteoporosis
abnormal bone minerailization in osteomalacia (rickets)
4 causes for primary osteoporosis?
- long term steroid use
- anticonvulsant
- anticoagulants
- thyroid replacement therapy
what symptoms/fractures can you get from osteoporosis?
- vertebral compression fractures associated with acute back pain, loss of height, kyphosis
- fractures of femoral neck
- fractures of distal radius (Colles fractures)
2 bone paths with normal lab values?
- osteoporosis
2. osteopetrosis
what two bone paths will have the opposite lab values (Ca2+, PO43-, PTH, except for ALP)?
osteomalacia/rickets and hypervitaminosis
2 causes for hypervitaminosis?
- oversupplementation
2. granulomatous dz (sarcoidosis)
explain how the lab values will be diff btw 1’ hyperparathyroidism vs 2’
1’: high PTH –> high Ca2+ –> low PO43-, high ALP
2’: high PO43- –> low Ca2+ –> high PTH, high ALP
in 2’ hyperparathyroidism, what causes high PO43- conc?
usually due to dec PO43- from ESRD
in 2’ hyperparathyroidism, what causes low serum Ca2+?
due to low activated vit D due to ESRD
