Bones, Joints & Soft Tissues (Martin) Flashcards
What type of ossification occurs in long bones?
Endochondral ossification; cartilage mold; new bone deposits are deposited at the bottom of growth plates leading to longitudinal growth
What type of ossification occurs in flat bones?
Intramembranous ossification; mesenchyme directly ossified by osteoblast; NO CARTILAGE; appositional growth
Osteomalacia
weakened, soft bone
Osteitis deformans
deforming bone-itis
Osteodystophy
difficult/bad growing bone
What is the most common type of collagen in osteoid?
type I collagen
Woven bone; increased cells and disorganized; produced rapidly (fetal development and repair); haphazard arrangement with less structural integrity; abnormal in adults
Lamellar bone; parallel collagen and strong; slow production; adult bone
In which decade of life do you tend to have more resorption of bone than formation?
fourth decade; see a decrease in skeletal mass
RANKL and OPG are expressed and produced by which cells?
Osteoblasts
Explain the pathophysiology of RANK?
receptor on osteoclast that activates NF-kB which promotes their survival and increases bone breakdown
Osteoprogenitor cells (osteocytes) produce which protein that triggers activation and production of OPG?
WNT proteins; they bind LRP5 and LRP6 on osteoblasts activates B-catenin and produces OPG; favors bone deposition/formation
Sclerostin
produced by osteoclasts; inhibits WNT/B-catenin; suppressing bone formation
What three hormones are important in bone formation?
estrogen, testosterone and Vit. D
What is the role of estrogen, testosterone and Vit. D in bone physiology?
they all favor bone formation
The role of M-CSF in bone homeostasis and remodeling?
M-CSF receptor on osteoclast that stimulates tyrosine kinase cascade; crucial for osteoclast generation
Dysostosis
localized disruption of migration and condensation of mesenchyme and differentiation into cartilage anlage
Supernumerary digit
extra bones or digits
Syndactyly or craniosynostosis
abnormal fusion of bones
What homeobox protein mutation is commonly associated with short terminal phalanges and a big toe?
HOXD13 mutation; brachydactyly
Achondroplasia
dwarfism; AD FGFR3 GOF mutation; short proximal extremities with normal trunk length, enlarged head and bulging forehead; NO change in longevity, intelligence or reproductive status
Thanatophoric dysplasia
most common death form of dwarfism; FGFR3 GOF mut (more severe phenotype); small chest cavity (respiratory insufficiency); die at birth or soon after
Osteogenesis Imperfecta involves which type of collagen?
Type I
Brittle bone disease
Osteogenesis imperfecta; deficiency in type I collagen will see BITE signs and symptoms; type I normal lifespan; type 2 most severe (die in utero); type 3 severe (if survive utero) and type 4 is mild
Osteogenesis imperfecta
brittle bone disease; deficiency in type I collagen; BITE signs and symptoms; accordion-like shortening of limbs
type I - COL1A1 mut
type II COL1A1 or COL1A2 mut (most severe) - respiratory problems (undeveloped lungs)
Treatment for osteogenesis imperfecta?
Surgical “rodding” of long bones; exercise and good nutrition; no smoking or steroid use
Pathology in osteopetrosis
decrease in bone resorption due to deficient osteoclast function causing diffuse, symmetric skeletal sclerosis
What is the mutation in achondroplasia?
Gain of function FGFR3 mutation
Defect in type II osteogenesis imperfecta?
there is no triple helix of collagen type I; uniformly fatal in utero (multiple intrauterine fractures)
Defect in type I osteogenesis imperfecta?
the collagen structure is normal, there is just less of it; these patients have a normal lifespan with most fractures occurring BEFORE puberty
What are the two types of osteopetrosis?
“marble bone disease”
1. Alber-Schonberg disease
2. Carbonic Anhydrase 2 deficiency
Alber-Schonberg disease
an AD osteopetrosis “marble bone disease”; mut in CLCN7 which encodes for a proton-chloride exchanger in osteoclast; decreased bone resorption leading to diffuse symmetrical skeletal sclerosis
What is the mutation in Alber-Schonberg disease?
mut in CLCN7 which encodes for a proton-chloride exchanger in osteoclast; decreased bone resorption leading to diffuse symmetrical skeletal sclerosis; an AD osteopetrosis “marble bone disease”
What is the typical clinical prevention of a patient with osteopetrosis?
diffuse symmetrical skeletal sclerosis; bones lack a medullary cavity and can present as an Erlenmeyer flask on imaging
Carbonic Anhydrase 2 deficiency
an AR osteopetrosis “marble bone disease”; lack CA2 that is needed for osteoclastic activity and renal tubular cells (renal tubular acidosis); decreased bone resorption leading to diffuse symmetrical skeletal sclerosis
What is a symptom that is seen in Carbonic Anhydrase 2 deficiency and NOT in Alber-Schonberg disease?
renal tubular acidosis because renal tubular cells also depend on CA2; both are osteopetrosis disorders
Why do you see repeated infections in osteopetrosis?
the bones lack a medullary cavity; there is no hematopoiesis = no immune cells (leukopenia); will see extra medullary hematopoiesis involving the spleen (hepatosplenomegaly)
Erlenmeyer flask on imaging as seen in osteopetrosis
Osteoporosis
severe osteopenia (below 2.5 SD mean peak bone mass); most common forms are senile and postmenopausal
What are the two most common forms of osteoporosis?
- senile - age related with low turnover (decreased activity of osteoblasts)
- postmenopausal - estrogen deficiency (increased osteoclast activity)
What are the 5 factors affecting bone mass in osteoporosis?
- Age - senile, decreased proliferation (low turnover)
- decreased physical activity - immobility, paralysis, astronauts in zero gravity
- genetics - LRP5 gene defect (rare)
- insufficient ca2+ intake (adolescent girls)
- Hormonal - post menopausal (estrogen deficiency)
Tamoxifen
treatment for breast cancer that can increase bone loss (drug induced osteoporosis)
Senile osteoporosis
age related with low turnover (decreased activity of osteoblasts); cortex is thinned by subperiosteal and endosteal resorption