Bones part 1 Flashcards
Rank pathway
Rank ligand (RANKL) on Osteoblast and marrow stroma cells
Rank receptor on Osteoclast precurosr and allows osteoclast generation and survival.
M-CSF pathway
MCSF secreted by OB
MCSF receptor allows OC generation and survival
WNT and B catenin pathway
WNT from marrow stromal cells
LRP 5 and LRP6 OB receptor bind WNT protein
secrete OPG which blocks Rank
basic multicellular unit (BMU)
local collection of OB, OC, and osteocytes
early bone formation dominates
adult undergo remodling: 10% year turnover
peak bone mass: early adulthood
Bone composition
calcium hydroxyapatite
organic matrix mostly type 1 collagen
types of bone: woven bone
random collagen deposition
rapid bone growth after healing fracture
resits forces in all directions
always pathologic in adults
Types of bone: lamellar bone:
ordered deposition
compact bone and spongy bone (calcinous)
replaces woven bone and stronger than woven bone.
Bone enzyme osteopontin (osteocalcin)
Unique to bone
levels parallel osteblast activity
bone enzyme: akaline phosphatase
from osteoblasts. Also in liver and placenta
Primary center of ossification in fetal life
center of bone
scendary center of ossification
physis or growth plate
bone formation
intramembranous ossification
direct from mesenchyme
appositional growth
anatomy: epiphysis
distal to grwoth plate
ataomy: metaphysis
beneath growth plate
anatomy: diaphysis
center
Dysostosis
local problems in migration of mesenchyme and their condensation. Fused finger.
HOXD13 defect
Dysplasia
global defect in regulation of skeletal organogenesis
growing an extra finger.
Cleidocrania dysplasia
autosomal dominant
RUNx2 (CBFA1) transcription factor defect
short stature
abnormal clavicles
supernumery teeth
wormian bone: extra sutral bones. located on the head.
achondroplasia
growth plate defect from paracrine cell defect
reduced chondrocyte proliferation in growth plate
FGFR3 point mutations: gain of function: Inhibits cartilage growth
90% are spontaneous mutation
most common from paternal allele
achondroplasia etiology
growth plate zones are narrowed and disorganized: premature bone deposition
appositional and intramembranous bone formation continues: create relatively thick cortical bone
FGFR3 point mutations: gain of function: Inhibits cartilage growth
Achondroplasia body design/physical signs
short stature
short proximal limbs
normal trunk length
enlarged head with bulging forehead
depression root of nose
normal longeitivity, intelligence, and reproductive status
thanatophoric dwarfism: etiology, and physical signs
most common lethal dwarfism with 1/20000 births
FGFR3 mutation gain of function
micromelic short bowed limbs
frontal bossing with macrocephaly
small underdeveloped chest with bell shaped abdomen ; respiratory failure
deminished chondrocyte proliferation.
clover leaf skull
LRP5: involvement in bone.
Receptor activates WNT/B catenin in OB: production of OPG (blocks RNKL) and increases bone mass
GOF of LRP5
GOF; cannot upregulate OC: autosomal dominant osteopetrosis type 1
LOF of LRP5
disease of inactive LRP5: osteoporosis pseudoglioma syndrome:
Skeletal fragility and loss of vision
Osteopetrosis etiology
“marble bone disease
diffuse systemic bone sclerosis
cannot acidify pit: carbonic anhydrase II (CA2) deficiency
defect in RANKL: not enough OC activity
LRP5 gain of function
spectrum from autosomal dominant benign to autosomal recessive “malignant”
Osteopetrosis pathology
bone despotion replaces medullary cavity: no room for heamtopoiesis: extramedually hematopoiesis
bulbous long bone: Erlenmeyer flask deformity
narrow neural foramina
brittle bones
Autosomal dominant benign osteopetrosis: overview
adolescent or adulthood
multiple fractures
mild anemia
hepatosplenomegaly
mild cranial nerve defects
can be treated with bone marrow transplant
Osteogenesis imperfecta: overview
group of type 1 collage diseases
“brittle bone disease”
affects other areas rich in type 1 collagen
mutations of alpha 1 or 2 chains: quantitative decrease or qualitative defect
most common type is autosomal dominant
extreme skeletal fragility vs child abuse
OSteogenesis imperfecta type 1: clinical features
autosomal dominant
normal stature with less fractures after puberty
blue sclerae from translucency of sclera
dentinogenesis imperfecta from dentin defect
hearing loss from abnormal ear bone and sensorineural deficit
joint laxity
compatible with normal lifespan
osteogenesis imperfecta type II-IV
autosomal dominnatn to recessive with varying degrees of disease
Type 2, 9, 10, 11 collagen disease
defect in hyaline cartilage
spectrum of disease: fatal due to joint destruction
mucopolysaccharidoses
defect in ezymes degrading dermatan sulfate, heparan sulfate, and keratan sulfate
abnormalties of hyaline cartilage
malformed bones
Osteoporosis effects and causes
increased bone porosity and decreased mass: increased risk of fracture
disuse: osteoporosis local
metabolic bone idsease: primary: senile post moenopausal, idiopathic
secondary: drugs, diabetes, endocrine disorders, malignancy liver or GI disease
X ray can detect only after 30-40% of bone loss
Ostepenia
decrease bone mass
osteoporosis
osteopenia to the point of risk of fracture
Osteoporosis: physical acitivty
disuse osteoporosis: localized from loss of stimuli for bone remodeling
problem with long term space flgiht
osteoporisis: genetic factors
Vit D receptor polymorphism
Osteoporosis nutrition
calcium deficiency during growth stunts peak bone mass
senile osteoporosis causes and effects and physical examination
sekeltal mass peak: young adult
mostly hereditary determined by vit. d receptor, collagen 1a1, estrogen receptor, etc.
physically activity, strength, diet, hormone state
slow decrease in bone mass over time: osteoblasts reduced metabolism
cortex thinned on all surfaces: cortex bone may look like cancellous bone
postmenopausal osteoporosis
30 years post menopause: 35% cortical and 50% trabeuclar bone loss. 1 in 2 women will have an osteoporotic frature
high turnover form of osteoporisis
decreased estrogen leads to increased inflammatory cytokines. Increased rankl and decreased OPG which causes more OC than OB activity.
estrogen replacement is protective.
risk vertebral body collapse.
Hyperparathyrodism
Increased activity of OC > OB
osteitis fibrosa cystica: severe disease
Primary and secondary hyperparathyroidism
primary hyperparathyroidsm: most commonly from adenoma
secondary parathyroidism (often from hypocalcemia) tends to be less severe
Hyperparathyroidms SX on the bone
entire skeelton affected
subperosteal resorption thins cortices
loss of lamina dura around teeth
X ray: bone loss radial aspect of middle phalanges of index and middle finger
X ray: osteopenia
Hyperparathryodism SX: Brown tumor
Brown tumor: bone replaced by fibrovascular tissue. Microfractures result in hemorrhage and healing. Granulation tissue, and hemosiderin
hyperparathyrodism histo and xray
in cancellous bone osteoclasts tunnel and dissect central trabeculae
xray will show a thining of the bones on the radial side.
Renal osteodystrophy pathology
increased or decreased OC/OB activity: delayed mineralization (osteomalacia) , osteosclerosis or osteoporosis
hyperparathyrodism
decreased vitamin D conversion to 1,25 OH2 vit D3
metabolic acidosis: increased release of CA2
Paget disease: Race. SX
mid adulthood caucasians from Us, europe,: 1% of US; 2.5 males in England
Most asymptomatic but may have pain
easily fractured
85% polyostotic
80% involve axial skeleton and proximal femur
Some evidence of paramyxovirus
some evidence of osteoclasts are hyperresponsive to stimuli
Paget disease stages: osteolytic stage
loss of bone mass
osteoclasts in haphazardly resorption pits
Very early stage: a Vshaped “blade of grass” lesion seen on x ray.
Paget disease stages: Mixed stage
osteolytic and osteoblastic.
Prominant osteoblasts and osteoclasts
Paget disease stages: Osteosclerotic stage
coarse thick irregular trabeculae
hallmark: mosaic pattern on lamellar bone: jigsaw puzzle like cement lines
Paget disease presentations on bone
may present with pain from microfractures
often incidental finding on x ray
increased alkaline phosphatase
normal CA and Po4
bone overgrowth can lead to: cranial nerve palsy. Heavy skull. (hard to pull up). severe secondary osteoarthritis. Chalk stick type fracture
Paget disease other presentations other
warm skin over affected bone with hypervasculatrity; polyostotic can create AV shunting. High output cardiac failure.
Tumors: benign: giant cell tumor, giant cell reparative granuloma, extraosseous hematopoiesis. Malignant: osteosarcoma and fibrosarcoma. 5-10% of patitnes with severe polyostotic disease
Paget disease tx
calcitonin and biphosphonates
fracture types
closed (simple)/Open (compound)
comminuted (fragmented)(
displaced
green stick: incomplete fracture of the distal and radial diaphasis.
Pathologic: secondary to disease
stress: slowly developing form repeated loads, eg marching
Fracture soft tissue callus (procallus)
hematoma fibrin creates framework
influx inflammation, fibroblasts, and capillaries
osteoprogenitor cells activated
no rigidity; easily disrupted
fracture soft tissue callus
wwoven bone is made
+/- cartilage for endochondral ossification
maximum girth of callus 3 wks
over time remodels to bear full weight
fracture complications
misaligned bone
infected, displaced or devitalized bone leasd to deformity
pseudoarthrosis: nonunion
Osteonecrosis (avascular necrosis)
infarction of bone and marrow
mechanisms all create ischemia: vessel injury (mechanical, arteritis, emboli), corticosteroids most common cause, increased intraosseou pressure
dead bone/fat is replaced by CA soaps
creeping substitution: slow bone growth: continued fractures and collapse of bone. slough articular cartilage
avascular necrosis casues
idopathic
corticosteroids
trauma
infection
dysbarsim
radiation
connective tissue disorders
pregnancy
gaucher disease
alcohol abuse
chronic pancreatitis
tumors
epiphyseal disease
sickle cell disease and other anemias1
avascular necrosis: medullary infarct
geographic necrosis
small silent and stable
large painful: dysbarism, sickle cell
avascular necrosis: subchondral infarct
chronic pain
wedge shaped subchondral bone. Often crack beneath preserved cartilage . Overlying cartilage nurtured by synovial fluid
secondary collapse lead to osteoarthritis
osteomyelitis: caused by
inflammation almost always from infection. Bacteria, virus, fungi, parasite. Pyogenic; almost always bacteria
bacteria reach bone by hematogenous (most common in children), direct extension, implantation
osteomyelitis: detection
lytic bone lesion with surround sclerosis
pyogenic osteomyelitis: caused by
50% culture negative
S aureus: 80-90% of culture positive
E coli, pseudomonas, klebsiella. GU infections and IV drug abusers
Mixed infections: surgery or compound fractures
H flu and group B strep in infants
salmonella in sickle cell disease
Pyogenic osteomyeltiis: inflammation and necrosis (age dependent)
initial acute inflammation and necrosis
location influenced by blood supply: neonate: metaphysis and or epiphysis. Can spread into joint through articular surface or adjacent structures
children: metaphysis. Subperiosteal abscess
adult: epiphyses and subchondral bone
Pyogenic osteomyelitis: sequestrum
sequestrum: dead piece of bone.
Pyogenic osteomyelitis: later chronic inflammation and fibrosis
Develop rimed by reactive bone.
Brodie abscess: small intraosseous abscess often in the cortex walled off by reactive bone.
Pyogenic osteomyelitis: involucrum
reactive surrounding bone
Pyogenic osteomyelitis: sclerosing osteomyelitis of garre
in jaw with extensive new bone formation
Pyogenic osteomyelitis presentation
acutely sick to unexplained fever
local pain
draining sinus. can develop squamous cell carcinoma
5-25% become chronic osteomyelitis. Complications include pathological fracture and sarcoma
TB osteomyelitis. Who. assocations.
third world, immunocompromised. Adolescents and young adults
US: older or immunocompromised
2% with TB have osteomyelitis
most common Potts disease: L/T spine. Break through discs to other vertebrae. Scoliosis and kyphosis.
Knees and hips second most common.
Syphilis of the bone
T. Pallidum and T pertenue (yaws)
congenital: affected at 5 mo; fully developed at birth
localize at enchondral ossification centers (osteochondritis) and periosteum (periostitis)
acquried syphills of the bone: involves bone in tertiary phase. Nose (saddle nose), palate, skull, tibia (saber shin), vertebrae, hands/feet
