Basic Science Flashcards
Factors that direct mesenchymal stem cells into osteoblasts
RUNX2, BMP
osteoblasts form bone under _ strain and _ oxygen tension
low, high
osteoblasts form cartilage under _ strain and _ oxygen tension
intermediate, low
osteoblasts form fibrous tissue under _ strain and _ oxygen tension
high, low
PTH effect on bone
Stimulates osteoblasts to form bone if pulsed, inhibits if constant
1,25 Vit D effect on bone
stimulates osteoclasts through RANKL to resorb bone
Calcitonin effect on bone
inhibits osteoclasts to resorb bone
RANKL is produced by _ and activates _
osteoblast, osteoclast
TNF-alpha function
inhibits osteoblasts
Wnt function
stimulates osteoblasts
Sclerostin is formed by _ and inhibits _
mature osteocytes, osteoblasts
Sclerostin is released in response to _, and decreased under _.
Low stress concentration, high stress concentration
Osteoclasts are derived from _.
Myeloid origin (hematopoietic) in macrophage lineage
_ (native hormone) binds RANKL to inhibit signalling
Osteoprotegerin
_ (pharmacologic agent) binds RANKL to inhibit signalling
Denosumab
Bone resorption occurs in this part of osteoclast
how ship lacunae where the matrix is acidified and destroyed
IL-1 _ osteoclasts
activates
IL-10 _ osteoclasts
inhibits
Most abundant non collagen protein in bone
Osteocalcin
Lysomal enzyme in osteoclasts that resorb bone
Cathepsin K
In bone provides tensile strength
collagen I
In bone provides compressive strength
calcium hydroxyapetite
Nutrient arteries supply the _ of bone
inner 2/3
Periosteal capillary arteries supply _ of bone
outer 1/3
Type of bone formation during distraction osteogenesis
intramembranous
Fracture callus is _ bone formationo
enchondral
Deficiency of this enzyme inhibits bone formation in Howship lacunae
Carbonic anhydrase
Physical cellular zones from epiphysis to diaphysis
reserve zone, proliferative zone, hypertrophic zone, Zone of provisional calcification
Achondroplasia affects this part of physis
proliferative zone
Growth hormone affects this part of physis
proliferative zone
This zone of physis widens in rickets
hypertrophic zone due to insufficient calcification
SCFE occurs through which zone?
Hypertrophic
SCFE in renal osteogenesis occurs in what zone?
metaphysis
B- cantenin increases _ osteoblast activity
increases
SOX9 controls _
chondrocyte production
PTH effect on sclerostin
Increase sclerostin (decreases osteoblast activity)
Calcitonin effect on sclerostin
Decreases sclerostin (increases osteoblast activity); calcitonin also decreases osteoclast activity to decrease bone resorption
tartrate resistant acid phosphate does what and is produced by what enzyme?
Acidifies bone matrix in howship lacunae; formed by carbonic anhydrase
Osteopetrosis is caused by a defect in _, thereby _.
carbonic anhydrase, decreasing bone resorption
Groove of Ranvier and Ring of Lacroix contribute to _.
Width growth at the physis
Enchondral bone formation _ involve a cartilage phase
does
intramembranous bone formation _ involve a cartilage phase
does not, formed directly from MSCs that differentiate into osteoblasts
In soft callus what type of collagen forms first?
Type II
BMP-2 is indicated for treatment in _
Acute open tibia fractures
BMP-7 is indicated in _
tibia non unions
Role of Cox-2 in bone?
Required for normal enchondral ossification
Effect of low intensity pulse ultrasound?
strengthens callus
Quinolone antibiotics effect on bone?
toxic to chondrocytes, inhibit fracture healing
TGF-B effect on osteoblasts
stimulates osteoblast to produce collagen, found in fracture hematomas
Highest compressive strength of any graft material
Calcium phosphate cement
Calcium sulfate cements are associated with _
wound drainage
Centigrays of radiation to prevent HO
600-800
Primary regulators of serum calcium
PTH and 1,25 VitD3
Cartilage in soft callus is degraded by _
MMP-13 secreted by chondrocytes
Systemic effect of PTH
increased Ca, Decreased Phosphate
Systemic effect of Calcitonin
Decreases calcium (no effect on phosphate)
Active form of Vit D
1,25 Vit D
Form of Vit D measured in serum tests
25 Vit D
liver does what conversion to Vit D
Vit D -> 25 Vit D
Effect of 1,25 Vit D
Increases intestinal absorption of Ca, Phosphate. Stimulates Osteoclasts via RANKL through osteblast binding
Where is PTH produced?
Chief cells of parathyroid
Where is 1,25 Vit D produced
proximal tubule of kidney
Where is calcitonin produced?
parafollicular cells of thyroid
What stimulates PTH production?
low serum Ca
What stimulates calcitonin production
high serum Ca
What stimulates 1,25 Vit D production?
PTH
Effect of PTH on kidney
Increased Ca resorption, increased phosphate excretion, 1,25VitD production; Net increase Ca, decrease Phosphate
Metabolic findings of hyperparathyroidism
high Ca, low Phosphate
Renal Osteodysphtrophy causes _ (2)
decreased 1,25 Vit D production, decreased Phosphate excretion
Overall effect of rickets
widening of physis through zone of provisional calcification and thin cortexes with bowing
Serum findings of nutritional rickets: Ca PTH Phosphate Alk Phos 25Vit D 1,25VitD
Ca: low to normal (decreased Intestinal absorption)
PTH: High (due to decreased intestinal Ca absorption)
Phosphate: Low (Increased kidney excretion from high PTH)
Alk Phos: High (from bone turnover of PTH)
25Vit D: low
1,25VitD: low
Serum findings of Ca deficient rickets: Ca PTH Phosphate Alk Phos 25Vit D 1,25VitD
Ca: decreased or normal
PTH: Increased (due to decreased Ca absorption)
Phosphate: decreased (due to high PTH)
Alk Phos: increased (due to high bone turnover)
25Vit D: normal
1,25VitD: high
Type 1 Hereditary Vit D Dependent Rickets is defect in _?
1alpha 25VitD hydroxylase that makes active VitD
Treatment for Vit D Dependent Rickets?
Oral 1,25VitD (Calcitrol)
Most common form of rickets
Familial hypophosphatemic rickets
Serum findings of familial hypophos rickets: Ca PTH Phosphate Alk Phos 25Vit D 1,25VitD
Ca: normal PTH: Normal Phosphate: decreased Alk Phos: 25Vit D 1,25VitD
Cause of familial hypophos rickets
Impaired renal tubular resorption and Vit D response
Type 2 Hereditary Vit D Dependent Rickets is defect in _?
intracellular Vit D receptor
Treatment for Hereditary Vit D Dependent Rickets is?
Burosmab (anti FGF 23 antibody), Phosphate
Osteoporosis Z score is
less than -2.5
Osteopenia Z score is
-1 - -2.5
Effect of Bisphosphanates
Direct inhibition of osteoclasts, prevents formation of ruffled border (where bone resorption happens), and causes apoptosis
Nitrogen containing bisphosphonates are _ times more potent than non nitrogen containing
1000
Specific risk of bisphosphonate therapy
AVN of jaw
Scurvy has what effect on the physis
widening of zone of provisional calcification
Paget disease is characterized by
abnormal osteoclast function with virus like inclusions in the cell
Clonazepam _ sclerostin
increases (thereby decreasing bone production)
Teriparatide is called _ and is a synthetic analog of _
Forteo; PTH
Contraindications to the use of Forteo (2)
Paget’s dz, previous history of bone mets
Myasthenia Gravis is a caused by?
IgG antibody to ACH receptor
Type I muscle fibers are:
Slow twitch, oxidative, red; high triglyceride content
Type I fibers are increased in _ activities
endurance
Type II fibers are
fast twitch, glycolytic, “white”
Type II fibers are increased in _ activities
high intensity, short duration
Immobilization causes what effect on muscle healing
atrophy
TGF-B has what effect on muscle healing?
stimulates myofibroblasts, increases fibrosis
What is Decorin?
proteoglycan in tendons that links adjacent collagen molecules, regulates tendon diameter, decreases TGF-B effect
First type of Collagen formed in tendon healing?
Type III
Order of nerve layers:
Axon, myelin sheath, endoneurium, fascicles, perineurium, epineurium
Neuropraxia is caused by:
local conduction block caused by ischemia, selective demyelination; reversible
Axonotemesis
Disruption of myelin sheath, epineurium intact, Mullerian degeneration distally
Neurotemesis
Complete nerve transection; Mullerian degeneration distally
4 zones for tendon to bone connection
Tendon, fibrocartilage, Sharpey’s mineralized fibrocartilage, Bone
Tendon healing weakest at what point
7-10 days after repair