Bones Patho Flashcards
What are the differences bt cortical and trabecular bone
Cortical bone
- hard outer layer
- compact bone tissue= high density
- Porosity 5-30%
- 80% of the total bone mass
Trabecular bone
- Allows room for blood vessels and marrow
- 20% of bone mass(10x surface area of compact bone)= low density
- Porosity of 30-90%
what are haversian and volkmann’s canals
haversian- interconnecting, longitudinal channels in bone tissue through which blood vessels, nerve fibers, and lymphatics pass.
volkmann’s- they run for the most part transversely, perforating the lamellae of the haversian system, and connect the canals of that system.
where are Haversian and osteons located
cortical bone
what is trabecular bone AKA
cancellous or spongy bone
does changes in the rate of bone turnover occur more in cortical or trabecular bone
trabecular
do all bones contain both cancellous & cortical elements
yes, but proportions can differ
where do long bones like the femur have the most bone turnover
much more at the end bc the shaft is mainly cortical bone whereas the ends are thin cortex with coarse cancellous bone prominent
what are 5 functions of the skeletal system
Mineral homeostasis Houses hematopoietic elements Mechanical support for movement Protects Viscera Determines body size and shape
what is the epiphysis, metaphysis, and diaphysis
Epi-extends from subarticular bone plate to base of growth plate
Meta-coarse cancellous bone from growth plate to diaphysis
Dia- body or shaft of the long bone
what zone of a long bone is most important in hematogenous infection, tumors, and skel malformations
metaphysis bc more cancellous bone
what are osteoprogenitor cells
precursors to osteoblasts
what are osteocytes
ostoeblasts surronded by organic matrix. They are important regulators of bone mass and have mechanotransduction function
what is bone tissue regulated by
Transcription factors
Cytokines
Growth factors
what is hydroxapatite
a complex phosphate of calcium that occurs as a mineral and is the chief structural element of bone
-Ca, phosphate, and OH-
what is osteocalcin
a protein component of bone
what is osteopontin
a protein component of bone
what are the layers of bone
circumferential lamellae- run parallel to the surface of the bone
concentric lamellae- bony plate that surrounds haversian canals
interstitial lamellae-Any of the layers of bone between adjacent Havers.
what is the role of B-catenin
anchors osteoblasts to bone
what are osteoclasts derived from
machrophages
what is BMP
Bone morphogenic proteins
- functions by activating osteoblasts
- used in meds to cause spinal fusion
what can occur with long term use of drugs that inc BMP
overgrowth and tumors
what is LRP 5/6
LDL receptor related proteins 5 and 6
-surface receptors on osteoblasts that function by activating osteoblasts
how long after a fx should you begin to see healing on Xray
4th week otherwise not healing correctly
osteoblasts have receptors that bind what
PTH, estrogen, Vit D, Leptin
what senses tension on a bone and what pathway makes the bone resist the tension (mechanotransduction)
osteocytes sense tension on bones and signal osteoblasts to build and prevent osteoporosis/fxs
what is the diff in woven and lamellar bone
woven is less strong and should only be found in new bone (healing fx, embryonic bone). It is always abn in adults
Lamellar bone is regualr-parallels alignment of collagen into sheets
what is osteocalcin
marker for osteoclast activity
when will you see density changes in a bone scan? what can be used to earlier monitor osteoporosis meds
bone density scans will take 2 yrs before changes are seen. osteocalcin can be checked earlier
what is a osteoid
bone matrix not yet mineralized; takes approx 12 days (mineralization lag time)
what must bind to activate osteoclasts
RANK ligand (on osteoblast) binds to RANK-R (on osteoclast precursor)= differentation(activation) of osteoclast
what blocks the RANK-RANK ligand interaction
osteoprotegrin cells (drugs can target this to prevent osteoporosis)
what is involved in osteoclast differentiation regulation
M-CSF (monocyte colony stimulation factor), IL-1, TNF (ODP)
how many nuclei are contained in mature osteoclasts
6-12
what is estorgens effect on RANK ligand activation
estrogen inc osteoprotegrin and dec RANK lignad activation= dec osteoclast activation
what are Howship lacunae
small depressions in bone where osteoclasts are found
what is the relationship bt osteoclasts and pH
Osteoclasts generate an acidic environment
Acid digests organic components
what are the 3 essentials for osteoclastogenesis
1) TNF related receptor RANK
2) RANK ligand
3) M-CSF (monocyte colony stim factor)
what is NF-kappabeta
RANK +RANKL activates NF-kappabeta
Signaling increasing oteoclastogenesis
what is the functional unit of bone? how does it change with aging
Composed of osteocytes, osteoblasts, and osteoclasts
Control bone formation and resorption
Early in live: bone formation dominates
Later in life: remodeling occurs
what % of the skeleton gets remodeled/yr
10% (but less with age)
when is typical peak bone mass
early adulthood
does bone resorption and formation occur at the same location
No, they occur on separate surfaces
what is the definition of osteoporosis? how does it affect cortical and trabecular bone
porous bones and reduced bone mass from dec thickness of cortex and reduction in number and size of trabeculae of cancellous bone
what are the diff types of osteoporosis
1) Type 1 (postmenopausal)=disrupted connections bt trabeculae from inc osteoclast activity
2) Type 2 (senile)= reduced trabecular and cortical` thickness from loss of osteoblast activity
3) Secondary form endocrine, neoplastic(MM), GI, Drugs
what is the BMD criteria for osteopenia and osteoporosis
Osteopenia-BMD 1-2.5 SD below the mean for young adults (Tscore=-1 to -2.5)
osteoporosis- BMD more than 2.5 SD below young adult mean (Tscore<-2.5)
how is the osteoporosis T score diff from the Z score
T score is developed from 30 yr female
Z score- age and gender is matched
where is the most common location for osteoporosis
Spine: because of the abundance of cancellous bone in the spine, osteoporotic changes are most conspicuous
Can lead to kyphosis (dowager’s hump)
what are the DEXA recommendations
Who should get a DEXA, (NOF 2013)
• Woman age 65 or older
• Man age 70 or older
• If you break a bone after age 50
• Woman of menopausal age with risk factors
• Postmenopausal woman under age 65 with risk factors
• Man age 50-69 with risk factors
Other
• An x-ray showing bone loss
• Back pain with possible break in spine
• Height loss of ½ inch or more within one year
• Total height loss of 1 ½ inches from your original height
what age related bone loss causes osteoporosis
0.5%-0.7%/yr
how does age affect vit D levels
As one ages there is a decrease in renal 1 alpha-hydroxylase and less conversion of vitamin D to its active form
what are calcium and vit D intake recommendations
Calcium
Adults under age 50: 1000mg
Adults 50 and over: 1200mg
Vit D
Adults under age 50: 400-800IU
Adults 50 and over: 800-1000IU
what type of vit D has the longer half life
D3: cholecalciferol
how are cytokines involved in type 1 osteoporosis
Cytokines stimulate osteoclast recruitment by increasing RANKL while diminishing expression of OPG.
what is the pathophys of type 1 osteoporosis
dec estorgen and inc IL-1, IL-6, TNF= inc expression of RANK ligand= inc osteoclast activity
what is the pathophys of type 2 osteoporosis
1) dec replicative activity of osteoprogenitor cells 2)dec sythetic activity of osteoblasts
3) dec biologic activity of matrix bound growth factors
4) reduced physical activity
what is raloxifene
estrogen R modulator primarily used for Breast Ca but can be used for osteoporosis
what are Alendronate, Risedronate, Ibandronate, and Zoledronic acid
bisphosphonates used to inhib osteoclasts by affecting proton pump
what is forteo
PTH analog- if given in intermittent exposure it actually stimulates osteoblasts
what is the risks associated with forteo
bone Ca so only give for 2yrs
what is denosumab
antibody to RANKL
what are the risks with bisphosphonates
the effects of bisphosphonates stay in the bone for 5yrs= inc risk for atypical fx
what endocrine conditions may cause osteoporosis
1) corticosteriods(cushings) =inhib osteoblasts and Ca absorption
2) hyperparathyroidism= osteoclast recruitment
3) hyperthyroidism= inc osteoclast activity
4) hypogonadism
how does alcoholism cause osteoporosis
inhib osteoblasts
what is pagets dz
Disease of bone remodeling with numerous osteoclasts and large active osteoblasts
Osteoclast mediated bone resorption followed by new bone formation(either solitary or multiple sites) and collagen arranged in woven pattern
Disorganized mosaic pattern bone with increased vascularity and fibrosis
what is thought to cause pagets dz
thought to be viral- paramyxovirus, canine distemper
but also genetic autosomal dom pattern with incomplete penetrance
-mutation in SQSTM1 gene which enhances RANK signaling=inc osteoclast activity
-RANKL and RANK/OPG mutations also found
what are the 3 phases of pagets dz
1)Initial osteolytic stage= lysis of cortex
2)Mixed osteoclastic-osteoblastic stage
Ends with predominance of osteoblastic activity and evolves into the next stage
Cortex thickened & accentuation of cancellous bone
3)Burnt-out quiescent osteosclerotic stage=little cellular activity leaving disorganized bones
what stage of pagets is considered the “hot” resorptive stage
1st (osteolytic) stage when osteoblast isotope take up occurs
what is the net effect seen with pagets dz
gain in bone mass with newly formed bone disordered and architecturally unsound.
what Xray effects occur with advanced pagets
thinner cortex earlier on but, with time, Affected portion is enlarged, sclerotic, and exhibits irregular thickening of both the cortical and cancellous bone.
- tibia often bows out.
- Axial skeleton and femur involved in 80% of cases
- Craniofacial enlargement
- Lysis in frontal and parietal bones:
- Spontaneous fractures (usually transverse)
what lab changes are expected with pagets
Alk Phos high, increase urinary hydroxyproline
[Ca2+] normal unless immobilized
besides fxs what other complications can result from Pagets
- Deafness (involvement of ossicles)
- Nerve entrapment (impingement of CN8 at foramen
- Spinal stenosis
- Osteogenic sarcoma: 0.7-0.9%
- Hypercalcemia (rare)
- Skull can become heavy and collapse over C1 vertebra resulting in: compression of brain and spinal cord
what is platybasia
flattening of the base of skull from pagets, impinges foramen magnum= compression of medulla and cord
what is pagetic steal
lightheadedness due to shunting of blood from brain to bone
what is pagets treatment
target osteoclasts- bisphosphonates, clacitonin, mithramycin
what is the net effect of PTH
1) PTH stimulates osteoblasts causing them to synthesize and secrete RANKL=RANKL binds to RANK in osteoclasts= Large amounts of PTH and continued RANKL prevents osteoclast apoptosis= Increase serum [Ca2+]
2) PTH= inc PO4 extretion and inc Ca reabsorption in kidney
what is the relationship bt PTH and vit D
PTH= inc hydroxylation of vit D in kidney= activation of vit D= inc Ca absorption in intestines, inc bone resorption, dec renal Ca excretion, and inc phosphate excretion
what is primary hyperparathyroidism? what typically causes it?
PTH raised inappropriately relative to [Ca2+]
may be Autonomous hyperplasia or tumor (Usually adenoma (85%))
what is secondary hyperparathyroidism? what typically casues it
Prolonged states of hypocalcemia resulting in compensatory hypersecretion of PTH
-usually from kidney failure=bones only source of Ca
why does renal dz lead to weak bones
1) dec active vit D
2) dec regulation of Ca and phosphorus= inc excretion of Ca and dec excretion of phosphorus
what causes familial hyperparathyroidism
mutaions in Calcium sensing-R (CASR) gene
is cortical or cancellous bone affected more in hyperparathyroid
cortical= thinned cortex
what is osteitis fibrosa cystica
the anatomic changes known from excess PTH
1)Dissecting osteitis:osteon hallowed out by osteoclasts
2) Osteitis fibrosa: trabecular bone reabsorbed and marrow replaced with fibrosis
3) Osteitis fibrosa Cystica: brown tumor (fibrosis with bleeding)
Xrays from osteitis fibrosa cystica can look like multiple myeloma with punch lesions. what test differentiates the 2
MM has benz proteins in the urine
what is dysotoses
A disorder in the development of bone
-Failure of a bone to develop:Congenital absence of a bone: phalanx, rib, clavicle
- Formation of extra bones: supernumerary digit (polydactyl)
- Fusion of two adjacent digits (syndactyly)
what occurs with a mutation to the homeobox gene (HOXD13)
Extra digit between third and fourth fingers and syndactyly
what occurs with loss of function mutations in RUNX2
RUNX2 Normally produces transcription factors important in osteoblastogenesis
Mutation results in cleidocranial dysplasia
- Patent fontanelles
- Delayed closure of cranial sutures
- Wormian bones: extra sutures
- Delayed eruption of secondary teeth
- Primitive clavicles
- Shortened height
what does mutation in the FGF receptor 3(chr 4) cause
Normally FGF3 inhibits cartilage proliferation
Mutations in FGFR3 cause constitutive activation and therefore suppresses growth=achondroplasia/dwarfism
how is FGFR3 mutation in dwarfism passed
autosomal dom on chr4 but 80% spontaneous mutation(mainly on paternal allele)
what are the manifestations of achondroplasia
Shortened proximal extremities
Trunk of relative normal length
Enlarged head with bulging forehead
Depression of the root of the nose.
Skeletal abnormalities usually not associated with changes in longevity, intelligence, or reproductive status
what is thanatophoria
the most common lethal form of dwarfism
what is the pathophys of thanatophoria
“gain of function” of FGFR3
Gene product gains a new and abnormal function
what are the manifestations of thanatophoria
Micromelic shortening of limbs
Frontal bossing
Macrocephaly
Small chest cavity=resp insufficiency
Bell shaped abdomen
what is type 1 collagen dz known as
Osteogeness imperfecta
-Most common inherited disorder of connective tissue
what does type 1 collagen dz affect
Principally affects bone
Other Type 1 collagen tissue also affected: joints, eyes, ears, skin, and teeth
where are the 4 types of collagen located
type 1= bONE
type 2= carTWOlage
type 3= thREEticulum
type 4= basement membrane
what are common s/sx of osteogeness imperfecta (type 1 collagen dz)
“Brittle” bone disease, too LITTLE bone, BLUE sclera
what is the pathogenesis of oseogeness imperfecta
point mutation affecting glycine residue in genes which code for the alpha-1 and alpha-2 chains of COLLAGEN 1
what is the inheritance pattern of oseogeness imperfecta
autosomal dominant
what are the diff osteogeness imperfecta types
Type 1: Autosomal dominant-decrease synthesis of alpha-1 chain
- Compatible with survival: Normal life span
- Childhood fractures which decrease in puberty
- Blue sclera, hearing loss(fusion of ossicles), dental imperfections (misshapen, bluish)
Type 2: Autosomal dominant or recessive-alpha 1 and 2 perinatal lethal (multiple intrauterine fractures) Type 3: Autosomal dominant 75%, recessive 25%-alpha 2 progressive, deforming Type 4: Autosomal dominant – short alpha 2 chain compatible with survival
mucopolysaccharidosis is a dz of what
a defect in folding and degradation of macromolecules, specifically a lysosome storage dz that dec enzymes that degrade
DERMATAN SULFATE
HEPARAN SUFLATE
KERATAN SULFATE
what anatomical changes result from mucopolysaccharidosis
Chiefly CARTILAGE disorders: short, chest wall, malformed bones
Undegraded GAGs accumulate in connective tissue, neurons, and hepatocytes.
what is osteopetrosis AKA
marble bone dz
what are the diff types of osteopetrosis(marble bone dz)
1)Autosomal Dominant: One type is due to CARBONIC ANHYDRASE deficiency= Carbonic Anhydrase is necessary for osteoclasts to generate protons from CO2 and water.
Relatively benign, some anemia
2)Autosomal Recessive: Usually affects the proton pump in osteoclasts
Severe, death due to anemia, cranial nerve entrapment, hydrocephalus and infection. Also see extramedullary hematopoiesis
why can anemia result from dec osteoclast activity
dec osteoclast= inc bone thickness= dec marrow fxn= anemia
what is chacteristic of the “marble” bones
- “MARBLE” bone, brittle, sclerosis (break like a piece of chalk) from dec osteoclast resorption
- Diffusely DENSE bone with Erlenmeyer Flask deformity of distal humerus.
why is osteopetrosis treated with bone marrow transplant
osteoclasts are derrived from monocytes
what is the similarities and difference bt ricketts and osteomalacia
both are vit D deficiency/dysfunction but ricketts is in children, whereas, osteomalacia is in adults
what is renal osteodystrophy
any bone disorder due to chronic renal disease
what are ricketts and osteomalacia predisposed to
fractures and pseudofractures(look like fx but only dec in Ca/vit D
what are the skeletal changes from chronic renal dz
Increased osteoclastic bone resorption
Delayed matrix mineralization (osteomalacia)
Osteosclerosis (fibrotic tissue replaced bone)
Growth retardation
Osteoporosis.
what are the 3 major types of renal osteodystrophy
High turnover osteodystrophy= Increased bone resorption and bone formation
Low turnover or aplastic disease= Adynamic bone (little osteoclastic and osteoblastic activity
Osteomalacia (mixed type of the two above)
what is the pathogenesis of renal osteodystrophy
Chronic renal failure causes phosphate retention and hyperphosphatemia
- Hyperphosphatemia induces secondary hyperparathyroidism
- Hypocalcemia due to decrease levels of vitamin D
- PTH markedly increases
- Induction of osteoclast activity
- Metabolic acidosis associated with renal failure stimulates bone resorption and release of calcium from bone matrix
what are the 3 phases of fractures
1)HEMATOMA: Rupture of blood vessels creates a hematoma which fills the fracture gap
Degranulated platelets and migrating inflammatory cells release PDGF, TGF-beta, FGF and interleukins which activate the osteoprogenitor cells in the periosteum, and medullary cavity.
2)SOFT CALLUS (“PRO”-CALLUS), ~1 week
Provides anchorage but no structural rigidity
3)HARD CALLUS (BONY CALLUS), several weeks
Maximum girth at end of second or third week
Woven bone then laminar bone
what are complications of fxs
PSEUDARTHROSIS:false joint at site of fx
INFECTION (especially OPEN [communicating] fractures)
Malunion: doesn’t heal in correct alignment
Nonunion: doesn’t heal at all
what is CEFAZOLIN (ANCEF)
cephalosporin given prophylactically before ortho surg
what is osteonecrosis AKA
AVASCULAR necrosis or ASEPTIC necrosis
what can cause osteonecrosis
Ischemia
- Trauma
- Steroids
- Thrombus/Embolism
- Vessel injury, e.g., radiation
- INCREASED intra-osseous pressure=vascular compression
- Venous hypertension too
what are the 2 types of infarcts that cause osteonecrosis
Medullary infarcts involve cancellous bone and marrow
Subchondral infarcts cause triangular segment of tissue undergoes necrosis
Overlying articular cartilage remains viable as it receives nutrition from synovia fluid
why is the cortex not affected in medullary infarcts
-Cortex is not affected because of its collateral blood flow
how do medullary and subchondral infarcts present
Medullary- Present clinically silent except for large ones occurring in Gaucher disease, dysbarism, and sickle cell anemia
subchondral-Present with pain that is initially associated only with activity but becomes progressively more constant as secondary changes occur
what is gaucher dz
autoimmune dz causing vasculitis
what is the progression of medullary and subchondral infarcts
medullary-Remain stable over time
subchondral-Often collapse and predispose to severe, secondary osteoarthritis
More than 10% of joint replacements performed are for treatment of complications of osteonecrosis.
what is the most common bacteria that causes osteomyelitis
Staph
what type of pt is more likely to get osteomyelitis from E. coli, Pseudomonas, and Kleb
GI infections and IVDA
what type of pt is more likely to get osteomyelitis from mixed infections
surgical procedures or open fxs
what type of pt is more likely to get osteomyelitis from H flu and strep B
neonates
what type of pt is more likely to get osteomyelitis from salmonella
sickle cell dz
what is vertebral osteomyelitis associated with
Septicemia Bacterial arthritis Pathologic fracture Squamous cell carcinoma, Amyloidosis
where is the most common site for hematogenous cause of osteomyelitis
metaphyseal area d/t inc blood supply.
If a otherwise healthy child gets osteomyelitis, what is the likely cause
Hematogenous spread (dental, dermal cut)
what is involucrum?
(New bone)
A layer of new bone growth outside existing bone seen in pyogenic osteomyelitis (a sheath around the necrotic sequestrum)
what is sequestrum
(dead bone)
a piece of dead bone that has become separated during the process of necrosis from normal/sound bone (fragment of necrotic bone embedded in the pus)
what should be considered if arthritic changes occur at an early age
may be caused by involucrum
what are potential complications of osteomyelitis
Subperiosteal abscess
Draining sinus: cloaca
Joint involvement
SEQUESTRUM (dead bone)-
INVOLUCRUM (new bone)-
what is cloaca
the hole formed in the bone during the formation of a draining sinus
what is POTTS dz
TB of the spine
what does congenital osteomyelitis result from
syphilis
what causes “sabre” shin
tertiary syphilis
