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Flashcards in MSK Mod 1B Deck (103):

what are included in the cellular componene of connective tissue

fibroblasts, osteocytes, chondrocytes


the extracellular matrix is made up of 2 componenets

1. 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

1. 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



osteoblasts also produce substances that do what? (other than type 1 collagen)

regulate balance of bone formation/resorption


osteoblasts are located along

1. trabecular surfaces (cancellous or spongy surface)
2. inner surface of haversian's canal
3. inner surface of the periosteum (active bone formation)


osteocytes are formed from



the small cavity the osteocyte is located in is known as



osteocytes make up how much of cells in mature human skeleton



osteocytes blood supply

via small capillaries located and are a functionally active cell of bone


3 functions of osteocytes

1. stimulate remodeling process of bone
serve as sensory mechanism for mechanical stimulus to bone
3. mantain homeostasis of the mineralized (calcificaation) bone


how do osteocytes stimulate remodeling process of bone

1. 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

1. osteocytes synthesize molecules to assist with bone calcification
2. 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

1. osteoclast secrete acid and lytic enzymes to breakdown and dissolve surrounding bone
2. osteoclasts have microvilli (brush border) projecting out from cell
3. elements of bone are resorbed into the osteoclast at he base of the microvilli
5. 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

-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

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

1. originiation/activation of BMU
2. initiation of osteoclastic acitivity
3. resorption forms small cavity
4. osteoblast maturation/recruitment
5. osteoid formation
6. 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

1. osteoporosis
2. osteomalacia
3. Paget's dz of bone


examples of osteochondroses

1. osteonecrosis (avascular necrosis)
2. apophysitis (epiphysitis)


4 types of pathologies of bone

1. metabolic disorders of bone
2. osteochondroses
3. infection of bone
4. 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



bone density values defined by WHO

normal >833mg/cm3
osteopenia = 833-648 mg/cm3
osteoporosis =


2 classificatinos of osteoporosis

1. 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

1. growth phase
2. consolidation phase
3. 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

-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?



which type of bone is more sensitive to post menopausal bone loss, trabecular or cortical



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

1. hormonal status
2. physical inactivity
3. genetics/ethnicity
4. meds
5. tobacco
6. alcohol
7. 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

-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

1. dual energy xray absorptiometry (DEXA)
-gold standard
-DEXA along does not help ID individuals who have greater risk of fx's
2. single photon absorptiometry
3. dual photon absorptiometry
5. quantitative US
6. CT
7. plain film xray = POOR SCREENING TOOL - only detects bone loss after significant loss has occurred


what is the WHO online fx risk



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


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

1. fx
2. deformity
3. arthritis
4. nerve dysfunction
5. pain