MSK 1B - Bone: Structure and Pathology Flashcards
What are all connective tissues composed of?
Cells
Extracellular Matrix
What is the cellular component of connective tissue?
Fibroblasts
Osteocytes
Chondrocytes
Etc.
What is the extracellular matrix made out of?
Non-fibrous component –> ground substance (gel-like); -glyco-
Fibrous component –> collagen/elastin
What does collagen do?
Provide tensile strength
What does elastin do?
Provide elastic properties
What are the celluar components of bone?
Osteoblasts
Osteocytes
Osteoclasts
What do obsteoblasts do?
Form new bone
How do obsteoblasts form new bone?
Produce type 1 collagen
Produce osteoid (non-mineralized bone matrix)
Fascilitate mineralization (calcification) of osteoid to complete process
When can you call an osteoblast an osteocyte?
Once surrounding bone matrix (osteoid) is mineralized
Where are osteoblasts located?
Trabecular surfaces (cancellous/spongy surface)
Inner surface of Haversian’s canal
Inner surface of periosteum (active bone formation)
What is the name of the small cavity where osteocytes are located?
Lacunae
How much of the human skeleton is comprised of osteocytes?
90%
What is the function of osteocytes?
Directly stimulate remodeling process of bone
Assist by secreting enzymes to dissoolve surrounding mineralized bone to prepare for bone remodeling
Serve as sensory mechanism for mechanical stimulus to bone
Maintain homeostasis of the mineralized (calcified) bone
How do osteocytes maintain homeostasis of the mineralized (calcified bone)?
Recieve nutrients from capillaries that maintain mineral homeostasis
Syntehesize molecules to assist w/ bone calcification
Where are osteoclasts found?
Howship’s lacunae –> depression seen in microscopic view (areas of bone resorption)
What is the function of osteoclasts?
Resorption of bone –> Ca2+ into blood stream; resorption of low quality/surplus bone
How do osteoclasts break down bone?
Secrete acid/lytic enzymes to brekdown and dissolve surrounding bone
have microvilli projecting out from cell –> bone resobred @ base of microvilli
What happens to bone that is resorbed into osteoclasts?
Released into capillaries to allow elements to be recycled into new bone @ different site
What happens to osteoclasts after resportion is complete?
Degenerates
Becomes dormant until needed again
What are the matrix components of bone (8)?
Collagen fibers
Proteoglycans
Bone morphic proteins (BMP)
Glycoproteins
Osteocalcin
Bone albumin
Growth factors (cytokines)
Calcium Hydroxyapatite (HAP)
What are the function of glycoproteins?
Assist in collagen fiber formation
How much collagen in bone is type 1 collagen?
90%
What is the function of type 1 collagen?
Gives bone tensile strength
Gives bone weight bearing (compressive) strength
What synthesizes and secretes type 1 collagen?
Osteoblasts
What are proteoglycans?
Large polysaccharides attached to protein
Where are proteoglycans found?
Between collagen fibers of bone
What is the function of proteoglycans?
Assist type 1 collagen in resisting compressive strength of bone
Play role in calcification/fluid balance by attracting calcium via ion exchange
What is the function of bone morphic proteins (BMP)?
Promote formation of osteoblasts from stem cells
Promote osteogenesis in osteoblasts
What is the function of osteocalcin?
Promote osteoclast activity therefore promoting bone resorption
What is the function of bone albumin?
Attracts fluid and maintains fluid balance in bone
What is the function of growth factors (cytokines)?
Play role in differentiation, activation, growth and turnover of bone (and other tissues)
What does IGF-1 stimulate in bone?
Long growth
What is calcium hydroxyapatite (HAP)?
Insoluble crystal that deposits within the collagen fibers
**end stage of calcium crystalization for mineralization (calcification)
What is the function of calcium hydroxyapatite (HAP)?
Gives compressive strength to bone
What is the bone multicellular unit (BMU)?
Cluster of cells that breakdown an area of the bone surface, then fills it w/ new bone
**multiple BMU clusters are activated/inactivated @ any given point in time and in different locations on a bone
What is the stimuli for the bone multicellular unit (BMU)?
Mechanical stress
Trauma
Cytokines/hormones –> PTH, IGF, IL-1, IL-6, PGE, Calcitriol, TNF, NO
Can occur at random
What do pre-osteoblasts produce?
RANK-L
What does RANK-L do?
Signal pre-osteoclasts to mature into active osteoclasts
What inhibits pre-osteoclasts maturing into active osteoclasts?
Osteoprotogerin (OPG)
What does resorption of bone by osteoclasts form?
Small cavity
**goes on for 2 weeks and then osteoclasts undergo apoptosis
What inhibits the resorption of bone by osteoclasts?
Estrogen
Calcitonin
**after menopause there is a estrogen deficiency and you have prolonged resorption
What promotes resorption of bone by osteoclasts?
Acidosis
What are some of the hormones, proteins, and other substances that promote osteoblasts maturation/activity?
PTH
WNT
BMPs
IGF
FGF
PDGF
Calcitriol
Runx2
GST-RANK-Ligand
TGF-Beta
What do active osteoblasts secrete to form the osteoid?
Collagen
Other components of bone matrix
How does the osteoid mature?
Calcium is slowly crystallized in stages
**Calcium hydroxyapatite (HAP) is final crystallized form that binds to collagen fibers
What is bone remodeling dependent on?
Osteoblast activity coupled w/ osteoclast activity
What is Wolff’s Law?
Mechanical stress leads to increased bone density
Removal of mechanical stress leads to bone loss
What are the metabolic disorders of bone?
Osteoporosis
Osteomalcia
Paget’s Disease of Bone
What are the 2 types of osteochondroses?
Osteonecrosis
Apophysitis
What is osteopenia?
Low bone mineral density (BDM) but not severe enough to be considered osteoporotic
What is the BMD value that is considered osteopenia?
Between -1 and -2.5
What is osteoporosis?
Severe disease in bone mineral density
What is the BMD value that is considered osteoporosis?
-2.5
What is osteomalacia?
Softening of the bone
What is osteopetrosis?
Increase in bone mineral density (too much)
What happens to cause osteoporosis?
osteoclastic activity > osteoblastic activity
What type of bone is usually affected by type1-postmenapausal primary osteoporosis?
Primarily cancellous bone
What type of bone is usually affected by type2-age related primary osteoporosis?
Cancellous and cortical bone loss
**usually pts > 75
What are the 3 phases of bone mass?
Growth phase - until growth plates close (90% of bone density)
Consolidation phase - bone density increases until peak bone mass is reached (10% of bone density)
Involution phase - gradual loss of bone density
When is peak bone mass commonly reached?
30 yo
After the peak bone mass is reached, what happens?
Short plateau of peak bone mass ~ 3 - 5 yrs followed by decrease in bone mass
When does bone loss begin for women?
Age 35 - 40 yo
Who rate of bone loss is higher, men or women?
Rate is equal (men start w/ higher amt so it takes them longer to reach osteoporotic levels)
How much bone loss per year is considered normal age related bone loss?
0.5 - 1%
When is the rate of bone loss in women accelerated?
After menopause d/t decrease in estrogen levels
During the 1st decade after menopause what is the rate of bone loss?
Can increase to 3 - 5% per year
**15% of total bone mass may be lost during this time period
What happens to the rate of bone loss after the 1st decade of menopause?
Rate of loss gradually slows
What are some secondary causes of bone loss?
Pathology
Meds (corticosteroids)
Nutrition deficiencies
What does the loss of estrogen after menopause cause?
Disruption of RANK-L and OPG homeostasis
**higher levels of RANK-L w/ reduced levels of OPG = increased osteoclastic activity
What are the regions most affected during osteoporosis?
Cancellous (trabecular) bone:
Vertebrae
Metaphysic of long bone –> wrist/femur are common fracture sites
What are some age related factors suggested to contribute to osteoporosis?
Decreased GH and IGF levels
Decreased androgens
Increased RANK-L and inhibited OPG
Lifestyle: poor nutrition and inactivity
What are the risk factors for osteoporosis?
Hormonal status (post-menopausal women)
Physical Inactivity
Genetics (peak bone mass/loss varies between individuals)
Meds (long term corticosteroid use)
Tobacco (inhibits osteoblastic activity)
Alcohol (inhibits osteoblast activity)
Diet/nutrition
What is the female triad of anorexia/bulemia that puts them at greater risk for osteoporosis?
Eating disorder
Amenorrhea
Osteoporosis
For every decrease of 1 SD in bone mass density tests, will increase the risk of fracture by how much?
1.5 - 3 times
What is a normal Bone mass density test value?
≤ 1 SD of the young adult mean
What is a osteopenia bone mass density test value?
Between 1 and 2.5 SD below the young adult mean
What is a osteoporosis bone mass density test value?
> 2.5 below the young adult mean
What is the gold standard to do bone mass density tests?
DEXA or dual energy x-ray absorptiometry
**x-ray is a poor screening tool b/c it only detects significant bone loss
What is osteomalacia?
Insufficient mineralization of bone
**not a loss, matrix doesn’t mineralize (calcify)
What causes osteomalacia?
Poor nutrition (ie poor vitamin D intake)
Intestinal disease that impairs absorption
Renal disease
Medications
Tumors
What will you see on x-ray in a patient w/ osteomalacia?
“Looser zones”
Milkman’s pseudofractures
Bowing of long bones
**oriented perpedicular to the long axis of the bone and don’t cross the entier bone
What are rickets?
Childhood osteomalcia
What is paget’s disease of bone?
Disease that results in bone deformation w/ associated complications
What is the most common onset of paget’s disease of bone and who is affected more, men or women?
> 50 yo
M > F (8:1) ratio
Pathologically what happens in paget’s disease of bone?
Excessive resorption is followed by excessive bone formation –> poor quality enlarged deformed bone
What are the potential complications of paget’s disease of bone?
Fracture
Defority
Arthritis
Nerve Dysfunction (if compressed in skull)
Pain
What is osteonecrosis (avascular necrosis - AVN)?
Death of bone d/t loss of blood supply
What is the most common site for osteonecrosis?
Femoral head
What are the early signs/symptoms of osteonecrosis (AVN)?
Often asymptomatic
- *chronic = gradual onset of pain
- *if fracture = acute onset of pain
What are the common causes of osteonecrosis (AVN)?
Post-traumatic
Steroid use
Alcohol use
Idiopathic
What is apophysitis?
a traction apophysitis of the secondary ossification center
What are the different types of apophysitis?
Osgood-Schlatter disease
Olecronon apophysitis
Sever’s disease
What happens w/ osgood-schlatter disease?
Patella tendon pulling on tibial tuberosity
What happens w/ olecranon apophysitis?
Triceps tendon pulling on secondary ossification olecronon (see a lot w/ young athletes)
What happens w/ sever’s disease?
Achille’s tendon pulling on the secondary ossification center of the calcaneous
What is osteomyelitis?
Inflammation of bone caused by bacteria or other infectious agents (fungi, parasites, viruses
What is acute osteomyelitis?
New episode of infection
What is chronic osteomyelitis?
Inffective or delayed treatment w/ relapsing episodes
What is exogenous osteomyelitis?
Trauma exposes bone to bacteria and other foreign substances
What is hematogenous osteomyelitis?
Infection is spread to bone from pre-existing systemic infection
**MC = staph aureus
Why is bone prone to osteomyelitis?
Physical arrangement of bone contains regions that immune defense mechanisms are unable to access
What is the inflammation response to osteomyelitis?
Similar to other infections: –> impairs BV/lymph vessels in area
What can the inflammation response to osteomyelitis cause in adults?
Can cause disruption of bone cortex
Potential for pathological fracture
Pathologically what can happen in children w/ osteomyelitis?
Formation of:
Sequestrum (piece of dea bone)
Involucrum (layer of new bone)
What happens in children w/ osteomyelitis that can cause sequestrum?
Inflammation can lift off periosteum from sub-periosteal abscess –> disrupts more of blood supply
Why would a involucrum form in kids w/ osteomyelitis?
The lifting off of periostium increaes osteoblastic activity –> new bone growth
Where is the most common place of osteomyelitis?
Adults = lumbar spine
Kids = metaphysis near growth plate in long bones (distal femur, proximal humerus, tibia, radium)
What are the signs/symptoms of of osteomyelitis in adults?
Back pain
Low grade fever
What are the signs/symptoms of osteomyelitis in children?
High fever
Local pain, redness, swelling
Describe primary benign bone tumors
Well-differentiated
Slower growing
Surrounded by sclerotic rim (bones attempt to contain tumor)
Don’t tend to produce constant progressive bone pain
What are examples of benign bone tumors?
Osteoid (osteoid osteoma or osteoblastoma)
Chondroid (enchondroma)
Fibrous (non-ossifying fibroma)
Mixed (osteochondroma)
Describe primary malignant bone tumors
Agressive
Fast growing (can spread to other areas)
Bone can’t contain tumor
What are some examples of malignant bone tumors?
things ending w/ sarcoma
What are the patterns of bone destruction of primary bone tumors?
Geographic = well defined margins surrounding clear lytic area
Moth Eaten = less defined margins, surrounding lytic or partially lytic area
Permeative = poorly defined margins; abnormal lytic bone merged throughout bone
