MSK Mod 1B Flashcards
what are included in the cellular componene of connective tissue
fibroblasts, osteocytes, chondrocytes
the extracellular matrix is made up of 2 componenets
- non-fibours componenet
2. fibrous componenet
what is the nonfibrous component of the extracellular matrix os connective tissue
usually gel-like substance “ground substance”
-ex. proteoglycans, glycoprotein, minerals
what is the fibrous component of the extracellular matrix of connective tissue
- collagen - provides tensile strength
2. elastin - provides elastic properties
function of osteoblasts
formation of new bone
osteoblasts produces what
type 1 collagen and non mineralized bone matrix (osteoid) into immediate area surrounding osteoblast
osteoblasts facilitates
mineralization (calcification) of osteoid to complete the process
once the surround bone matrix (osteoid) is mineralized the osteoblast is now referred to as an
osteocyte
osteoblasts also produce substances that do what? (other than type 1 collagen)
regulate balance of bone formation/resorption
osteoblasts are located along
- trabecular surfaces (cancellous or spongy surface)
- inner surface of haversian’s canal
- inner surface of the periosteum (active bone formation)
osteocytes are formed from
osteoblast
the small cavity the osteocyte is located in is known as
lacunae
osteocytes make up how much of cells in mature human skeleton
90%
osteocytes blood supply
via small capillaries located and are a functionally active cell of bone
3 functions of osteocytes
- stimulate remodeling process of bone
serve as sensory mechanism for mechanical stimulus to bone - mantain homeostasis of the mineralized (calcificaation) bone
how do osteocytes stimulate remodeling process of bone
- directly signal steps in bone remodeling
2. assist by secreting enzymes to dissolve surrounding mineralized bone to prepare for bone remodeling
how do osteocytes maintain homeostasis of mineralized bone
- osteocytes synthesize molecules to assist with bone calcification
- osteocytes receive nutrients from the capillary blood supply which are needed to maintain mineral homeostasis
where are osteoclasts located
Howship’s lacunae
- depressions seen in microscopic view that represent areas of bone resorption
function of osteoclast function
resorption of bone
how do osteoclasts resorb bone
- break down bone allowing release of calcium into blood stream
- break down/resorption of inferior (poor quality) bone or surplus bone
osteoclast mechanism of bone resorption
- osteoclast secrete acid and lytic enzymes to breakdown and dissolve surrounding bone
- osteoclasts have microvilli (brush border) projecting out from cell
- elements of bone are resorbed into the osteoclast at he base of the microvilli
- the osteoclast eventually release the bony elements in the capillaries to allow the elements to be recycled into new bone at a different site
in different pathologies like metastatic bone dz and multiple myeloma - what is responsible fore the bone loss
osteoclast activity
what are collagen fibers
- how many types
- synthesized/secreted by
- arrangement
- part of the matrix component of bone
- 14 different types ID’d in body
- synthesized and secreted by osteoblasts
- fibers are arranged in fibril network allowing resistance against tensile and compressive forces
what type of collagen accounts for 90% of collgen in bone
Type 1
role of type 1 collagen in bone
responsible for tensile strength of bones as well as weight bearing (comrpressive) sterngth)
what are proteoglycans
- large polysaccharides attached to protein
- located bw collagen fibers of bone
- arrangement and location bw collagen fibers also assist in resisting compressive strength of bone
function of proteoglycans
play a role in calcification/fluid balance by attracting calcium (via ion exchange)
what are BMP’s
bone morphic proteins
-many types: BMP-2, BMP-6, BMP-9
function of BMP’s
promote formation of osteoblasts from stem cells, osteogenesis in osteoblasts
clinical application of BMPs
pharmaceutical intervention strategies for difficult/poor fracture
all connective tissue is composed of what two things?
cellular componenet and extracellular matrix
what are glycoproteins
- found where
- examples
- function
many glycoproteins found in the found in bone
- ex. sialoprotein, laminin, osteonectin, alpha-glycoprotein
- function: assist in collagen fiber formation, may assist in calcification
what is osteocalcin
produced by osteoblasts (part of communication bw osteoblasts and osteoclasts
-function: promotes osteoclast activity therefore promotes bone resorption
what is the function of bone albumin
attracts fluid and maintains fluid balance in bone
transports hormones, ions and other metabolites to/from bone cells
examples of growth factors
aka cytokines
-transforming growth factor (TFG-beta), TFG - alpha, insulin growth like factor (IGF-1), tumor necrosing factor (TNF), interleukins, interferon-gamma
function of growth factors
play role in differentiation, acitivation, growth and turnover of bone (and other tiessue)
-ex. IGF-1 affects all cells of body & involved in stimulus f long growth (facilitates signaling of GH)
what is an example of bone minerals
calcium hydroxyapatite(HAP)
- end stage of calcium crystallization for mineralization (calcification)
- the HAP is an insoluble crystal that deposits within the collagen fibers
- physical characteristics account for the compressive strength of bone
what is a BMU
bone multicellular unit
- cluster of cells that breakdown an area of the bone surface and then fills it with new bone
- multiple BMU clusters are activated/ inactivated at any given point in time and in different locations on a bone
bone remodeling steps
- originiation/activation of BMU
- initiation of osteoclastic acitivity
- resorption forms small cavity
- osteoblast maturation/recruitment
- osteoid formation
- mineralization/maturation of osteoid
bone remodeling steps - origination/activation of BMU
osteocytes will signal the start of BMU acitivity
- stimulus - mechanical stress, trauma, cytokines/hormones or may occur at random
ex. PTH, IGF, IL-1, IL-6, PGE, calcitriol, TNF, NO
bone remodeling steps - initiations of osteoclastic activity
pre-osteoblasts are formed and produce RANK-L
- RANK-L signal pre-osteoclasts to mature into active osteoclasts
- OPG (osteoprotogerin inhibits this step) - OPG is produced by mature osteoblasts
beon remodleling steps - resorption forms small cavity
the osteoclast continues to resorb bone for about two weeks
eventrually undergo pre-programmed death (apoptosis)
clinical application of bone remodeling - resorption forms small cavity
- estrogen and calcitonin inhibit this step and slow resorption
- post menopausal estrogen deficiency prolongs resorption and allows osteoclast to keep breaking down bone
- acidosis promotes osteoclast resorption
bone remodeling steps - osteoblast maturation/recruitment
hormone, proteins and other substances promote osteoblast maturation/activity
ex. PTH, Wnt, BMPs, IGF, FGFs, PDGFs,calcitriol, Runx2, GST-RANK-Ligand, TGF-beta
bone remodeling steps - osteoid formation
active osteoblasts secrete collagen and otehr compenents of bone matrix
bone remodeling steps -mineralization/maturation of osteoid
calcium, phosphate and other ions are necessary for mineralization of osteoid
- calcium is crystallized in stages
- calcium hyroxyapatite (HAP) is final crystallized form that binds to the collagen fibers
bone remodeling is dependent on what two acitivites
osteoblast activity coupled with osteoclasts activity
the balance bw osteoblats and osteoclasts determines what
formatin/shape of new bone
what are new strategies for pharmaceutical intervention to target slow bone loss
the communicator molecules (cytokine and proteins) bw osteoblasts and osteoclasts
metaoblic disordres of bone
- osteoporosis
- osteomalacia
- Paget’s dz of bone
examples of osteochondroses
- osteonecrosis (avascular necrosis)
2. apophysitis (epiphysitis)
4 types of pathologies of bone
- metabolic disorders of bone
- osteochondroses
- infection of bone
- tumors of bone and related tissue
what is osteopenia
low BDM (bone mineral density) but not severe enough to be considered osteoporotic -BMD of more than 1SD but thess than 2.5 SD
what is osteoporosis
severe decrease in BMD
- BMD value of 2.5 SD or more below adult mean
what is Osteomalacia
softening of bone
what is osteopetrosis
increased BMD
osteoclastic activity vs osteoblastic activity in osteoporosis
clastic>blastic
bone density values defined by WHO
normal >833mg/cm3
osteopenia = 833-648 mg/cm3
osteoporosis =
2 classificatinos of osteoporosis
- primary
2. secondary
what is primary osteoporosis
generalized decreased bone density unrelated to any underlying dz or condition
two types of primary osteoporosis
type 1 - post-menopausal - affects cancellous bone
type 2 - age related; typical in pts >75yo; will see both cancellous and cortical bone loss
what is secondary osteoporosis
bone density loss secondary to med or dz
3 phases of bone mass
- growth phase
- consolidation phase
- involution phase
what is the growth phase of bone mass
continues until growth plates are closed
90% of bone density is reach in growth phase
what is the consolidation phase of bone mass
bone density continues to increase until reaches peak bone mass
-remaining 10% of bone density occurs during this phase
what is the involution phase of bone mass
- gradual loss of bone density is multi-factorial
- normal and pathological causes
what is peak bone mass
PBM
- bone formation occurs at faster rate than bone resorption
- peak bone mass is commonly reached by 30 yrs of age
- short plateau of peak bone mass - approx 3-5 years
- clinical poor dietary/exercise lifestyle in teens/20s result in lower peak bone mass
what is the involution phase
bone loss
what is age related bone loss
normal bone loss with age
bone loss in men/women usually begins at what ages
35-40yo following a short plateau of bone density furing early 30s
rate of age related bone loss
age related bone density loss if fairly equal bw male and female
men start out a higher PBM so don’t reach osteoporotic level as soon as women
post menopausal bone loss
rate of bone loss in women is accelerated after menopause
-d/t decreased estrogen levels associated with post menopause causes increased rate of bone density loss
(estrogen has a protective effect on bone density)
during 1st decade of menopause & rate of bone loss
bone loss accelerates during 1st decade
- rate of loss may increase to 3-5% / year
- 15% of total bone mass may be lost during 1st decade post menopause
- this is approx 40-50% of the total expected lifetime bone density loss of a female
- rate gradually slows down after 1st decade
pathogenesis of osteoporosis - post-menopause
- estrogen loss disrupts RANK-L with reduced levels of OPG
- clinical: drug - raloxifene stimulates OPG production
regions of bone loos in post menopausal osteoporosis
most significant in cancellous (trabecular) bone
-vertebra, metaphysic of long bone (wrist and femur comon fx sites)
pathogenesis of osteoporosis - age related bone loss
numerous age related factors suggest to contribute
- decreased GH and IGF levels
- decreased androgens
- increased RANK-L and inhibited OPD
- lifestyle - poor nutrition and inactivity = osteocytes are stimulated with mechanical stress
- poor vitamin D calcium and other nutrients
meds that can cause bone loss
corticosteoids and immunosuppressants can alter RNKS-L and OPG balance
other metabolic/systemic disorders that can cause bone loss
RA, metastatic cancer also alter RANK-L and OPG balance
which type of bone is more sensitive to conditions that alter osteoblast and osteoclast acitivity trabecular or cortical bone?
trabecular bone - large surface are and not large bone mass to begin with compared to cortical bone
which type of bone has a larger percent of bone loss, trabecular or cortical?
trabecular
which type of bone is more sensitive to post menopausal bone loss, trabecular or cortical
trabecular
bone loss patterns - women - % of each type of bone that is lost
35-50% of trabecular bone mass
25-30% of cortical bone mass
bone loss patterns - men - % of each type of bone that is lost
15-45% of trabecular bone mass
5-15% of cortical bone mass
osteoporosis risk factors
- hormonal status
- physical inactivity
- genetics/ethnicity
- meds
- tobacco
- alcohol
- diet nutrition
how is hormonal status a osteoporosis risk factors
- post menopausal women have decrease estrogen levels
- 5-8 years after menopause women have accelerated bone loss rate (greater than 1% per year)
- HRT most effective during this time period
- men have much more gradual loss of testosterone thus have slower steady rate bone loss
how is physical inactivity a osteoporosis risk fact?
- throughout all phases of lifespan
- low activity in aage groups
-peak bone mass and loss has predetermined rates that will vary bw indviduals
-ethinic groups appear to have differences
how are meds osteoporosis risk facotrs
- steriods
- large loss occurs during first 6monnths of use then rate slows
- they impaire osteoblast and incresae osteoclast acitvity
how is tobacco an osteoporosis risk factor
imparis bone progenitor cells thus inhibiting osteobalstic activity
how is alcohol an osteoporosis risk factor
impairs osteoblast activity
-also imparis calcium absorption and increas renal excretion of calcium
how are diet and nutrition osteoporosis risk factors
- low calcium intake in growing years
- anorexia/bulimia in females - amenorrhea & reduced estrogen
what is the female triad
eating disorder, amenorrhea, osteoporosis
osteoporosis evaluation
BMD tesets
what are BMD tests
-statistical technique to measure the number of standard deviations from the population average
calssifications of osteoporosis
normal: BMD: 1SD but 2.5 below the young adult mean
types of BMD tests
- dual energy xray absorptiometry (DEXA)
- gold standard
- DEXA along does not help ID individuals who have greater risk of fx’s - single photon absorptiometry
- dual photon absorptiometry
- quantitative US
- CT
- plain film xray = POOR SCREENING TOOL - only detects bone loss after significant loss has occurred
what is the WHO online fx risk
FRAX
what is osteomalacia
insufficient mineralization of bone
-no loss of bone, matrix just doesn’t mineralize
etiology of osteomalaica
poor nutrition - poor vit D intake
- intestinal dz that imparis absorption
- renal dz
- meds
- tumors
osteomalacia on x=-ray
Looser’s zones or milkman’s pseudo fractures = lesions composed of poorly mineralized osteoid matrix and are not true fx’s or stress fractures. oriented perpendicular to the long axis of the bone; bowing of long bones
what is rickets
childhood osteomalacia
what is Paget’s Dz of bone
results in bone deformation with associated complications
onset >50 yo
M>F (8:1)
pathology of paget’s dz
- distortion of bone resorption and formation of trabecular bone
- communication bw osteoblasts and osteoclasts are altered
- excessive resorption is followed by excessive bone formation
result: enlarged deformed bone of poor quality; disorganized collagen fibers, poor mineralization
potential complications of Paget’s dz
- fx
- deformity
- arthritis
- nerve dysfunction
- pain
