Lecture 8

Question 1

OSTEOCLAST FORMATION REGULATION AND ACTIVITY (3 STEPS)

Answer 1

1. ) PROLIFERATION/DIFFERENTIATION - MONONUCLEAR PRECURSOR CELLS W/ HEMATOPOIETIC LINEAGE FUSE => MULTINUCLEATED OSTEOCLASTS
2. ) ACTIVATION OF OSTEOCLAST PRECURSOR WHEN RANKL BINDS TO RANK ON OSTEOCLAST SURFACE (OPG CAN INTERFERE W/ THIS REACTION AND STOP OSTEOCLAST ACTIVATION BY BINDING TO RANKL)
3. ) RUFFLED MEMBRANE SECRETES H+ ENZYMES => ACIDIC ENVIRONMENT (PROMOTES DEGRADATION OF ORGANIC/INORGANIC PORTION OF BONE INTO COMPARTMENT

Question 2

RUFFLED MEMBRANE

Answer 2

• CA CATALYZES FORMATION OF H2O AND CO2 W/IN RUFFLED MEMBRANE AND COMBINES THEM TO FORM BICARBONATE (PROVIDES H+ IONS FOR ACIDIC ENVIRONMENT)
• DEGRADATION PRODUCTS FROM BREAKDOWN OF BONE INTO CA2+ AND PO4(3-) AND COLLAGEN FRAGMENTS ARE REABSORBED BY RUFFLED MEMBRANE AND EXCRETED VIA VESICULAR EXCRETION

Question 3

ENZYMES INVOLVED IN OSTEOCLASTIC BONE BREAKDOWN

Answer 3

1.) LYSOSOMAL ENZYMES
2.) MATRIX METALLOPROTEINASES
RELATIONSHIP BETWEEN ENZYMATIC AND CHEMICAL ACTIVITY IS IMPORTANT

Question 4

TUMOR CELL EFFECTS ON OSTEOCLASTIC ACTIVITY

Answer 4

TUMOR CELLS PRODUCE FACTORS (PTHrP - PARATHYROID HORMONE-RELATED PROTEIN) THAT PROMOTE FORMATION/ACTIVATION OF OSTEOCLASTS => BONE RESORPTION AND RELEASE OF FACTORS BY BONE MATRIX (TGF-β) WHICH STIMULATES TUMOR CELL PROLIFERATION

Question 5

PTHrP

Answer 5

BLOCKS OPG AND ACTIVATES RANKL

Question 6

BONE GROWTH

Answer 6

BONE GROWS IN LENGTH @ THESE VARIOUS SITES -
1) CARTILAGE GROWS ON THE ENDS OF THE ARTICULAR CARTILAGE
2) CARTILAGE REPLACED BY BONE ON THE INSIDE OF THE ARTICULAR CARTILAGE
3) CARTILAGE GROWS AT THE EPIPHYSEAL PLATE OUTER EDGE
4) CARTILAGE REPLACED BY BONE AT THE EPIPHYSEAL PLATE INNER EDGE
THIS OCCURS UNTIL EPIPHYSEAL PLATES (COMPOSED OF HYALIN CARTILAGE) CLOSE

Question 7

BONE REMODELING IN SPONGY/CORTICAL BONE

Answer 7

DIAPHYSIS IS REMODELED -
SPONGY BONE IS REMODELED EVERY 3-4 YEARS
CORTICAL BONE IS REMODELED EVERY 10 YEARS
PROCESS IS CONTINUAL - NEVER AT METABOLIC REST
PRODUCES LYSOSOMAL ENZYMES AND ACIDS

Question 8

BONE REMODELING

Answer 8

1. ) BONE RESORBED AT BONE HEAD/NECK JUNCTURE
2. ) BONE ADDED BY APPOSITIONAL GROWTH AT THE SURFACE OF THE EXTERIOR DIAPHYSIS
3. ) BONE RESORBED ON THE INTERIOR SURFACE OF THE DIAPHYSIS

Question 9

REMODELING UNITS

Answer 9

MADE UP OF A COMPOSITE OF OSTEOBLASTS AND OSTEOCLASTS

Question 10

EPIPHYSEAL PLATE CARTILAGE ORGANIZATION

Answer 10

Real People Have Career Options

1. ) RESTING ZONE - SMALL INACTIVE CARTILAGE CELLS
2. ) PROLIFERATION ZONE - QUICKLY DIVIDING (REPEATED MITOSIS) CHONDROBLASTS (PUSH EPIPHYSIS AWAY FROM DIAPHYSIS => LENGTHENING)
3. ) HYPERTROPHIC ZONE - OLDER CHONDROCYTES ENLARGE AND SIGNAL TO THE SURROUNDING MATRIX TO CALCIFY
4. ) CALCIFICATION ZONE - MATRIX BECOMES CALCIFIED AND CHONDROCYTES DIE LEAVING BONE-LIKE TISSUE (NOT BONE YET)
5. ) OSSIFICATION ZONE - OSTEOCLASTS DIGEST CALCIFIED CARTILAGE AND OSTEOBLASTS REPLACE IT W/ ACTUAL BONE TISSUE IN THE SHAPE OF CALCIFIED CARTILAGE => BONE TRABECULAE

Question 11

FUSION OF EPIPHYSIS

Answer 11

AT FULL BONE LENGTH CELLS IN EPIPHYSEAL CARTILAGE STOP PROLIFERATING AND BONES OF DIAPHYSIS AND EPIPHYSIS THEN BECOMES CONTINUOUS

Question 12

ACHONDROPLASIA

Answer 12

DEFECT IN CARTILAGE FORMATION (MOST COMMON CAUSE = DWARFISM)

Question 13

SALTER-HARRIS FRACTURES

Answer 13

INVOLVE EPIPHYSEAL PLATES (INTERFERES W/ GROWTH AND HEIGHT)

Question 14

OSGOOD-SCHLATTER DISEASE

Answer 14

STRESS ON EPIPHYSEAL PLATES IN THE TIBIA LEAD TO EXCESS BONE GROWTH AND A PAINFUL LUMP IN THE BONE

Question 15

SOMATOTROPIN

Answer 15

PRIMARY GROWTH FACTOR THAT AFFECTS BONE GROWTH
STARTS IN THE HYPOTHALAMUS
-TROPIN = TO NOURISH/STIMULATE

Question 16

HYPOTHALAMIC PITUITARY AXIS

Answer 16

RELEASES GROWTH HORMONE RELEASING HORMONE (GHRH) WHICH CAUSES A RELEASE OF SOMATOTROPIN FROM THE ANTERIOR PITUITARY WHICH THEN TRAVELS TO THE LIVER AND STIMULATES THE RELEASE OF NEW GROWTH FACTOR, INSULIN-LIKE GROWTH FACTOR WHICH ACTS AS A NEGATIVE FEEDBACK LOOP AND BINDS TO THE HYPOTHALAMUS TO TELL IT TO STOP RELEASING GHRH VIA SOMATOSTATIN (GROWTH HORMONE INHIBITING HORMONE) AND PROMOTES FEMUR AND MUSCLE GROWTH

Question 17

GIGANTISM

Answer 17

EXCESSIVE GH SECRETION THAT STARTS IN YOUNG ADULTS/ADOLESCENTS
RARE, RESULTING FROM A TUMOR OF SOMATOTROPES
PITUITARY DISORDER

Question 18

ACROMEGALY

Answer 18

EXCESSESIVE SECRETION OF GH IN ADULTS AS A RESULT OF A BENIGN PITUITARY TUMOR
CLINICAL SIGNS -
1.) OVERGROWTH OF EXTREMITIES
2.) SOFT TISSUE SWELLING
3.) ABNORMALITIES IN JAW STRUCTURE - MAX/MAN PROGNATHISM (ONLY AFFECTED DUE TO 2˚ CARTILAGE)
4.) CARDIAC DISEASE
CAUSES HYPERGLYCEMIA - NO EFFECTS ON HEIGHT B/C EPIPHYSEAL PLATES ARE ALREADY CLOSED

Question 19

ESTROGEN’S ROLE IN CLOSURE OF EPIPHYSEAL PLATES DURING EARLY SEXUAL MATURATION

Answer 19

ESTRADIOL-17β (E2) HAS AN INDIRECT EFFECT ON THE E2/α-ESTROGEN RECEPTOR WHICH STIMULATES GROWTH HORMONE SECRETION AND YIELDS INCREASED LONGITUDINAL BONE GROWTH

Question 20

ESTROGEN’S ROLE IN CLOSURE OF EPIPHYSEAL PLATES DURING LATE SEXUAL MATURATION

Answer 20

E2 HAS A DIRECT EFFECT ON THE E2/α-ESTROGEN RECEPTOR WHICH INHIBITS CHONDROCYTE PROLIFERATION AND YEILDS A CESSATION OF LONGITUDINAL BONE GROWTH

Question 21

EPIPHYSEAL PLATE CLOSURE IN MALES

Answer 21

ANDROSTENEDOINE ————-> ESTRONE (LESS POTENT)
TESTOSTERONE ————> ESTRADIOL
SAME PROCESS AS FEMALES BUT GROWTH OCCURS FOR LONGER PERIODS OF TIME IN MALES

Question 22

BONE RESORPTION ESSENTIAL POINTS

Answer 22

RESORPTION BAYS - GROOVES FORMED BY OSTEOCLASTS AS THEY BREAK DOWN BONE MATRIX

Question 23

RESORPTION INVOLVES OSTEOCLAST SECRETION OF

Answer 23

1. ) LYSOSOMAL ENZYMES THAT DIGEST ORGANIC MATTER
2. ) HCL THAT CONVERTS CA2+ SALTS INTO SOLUBLE FORM
3. ) BROKEN DOWN PRODUCTS ARE ENDOCYTOSED AND RELEASED INTO INTERSTITIAL FLUID/BLOOD

Question 24

BONE RESORPTION MECHANISM

Answer 24

1. ) CA SYNTHESIZES HCO3- FROM CO2 AND H2O
2. ) HCO3- IS CHANNELED TO THE SITE OF CACO3 SYNTHESIS
3. ) POLYPHOSPHATE IS FORMED AND STORED W/IN CELL VESICLES AND NEUTRALIZED BY METAL IONS
4. ) POLYPHOSPHATE IS RELEASED INTO EXTRACELLULAR SPACE AND HYDROLYZED BY ALKALINE PHOSPHATE
5. ) ORTHOPHOSPHATE AND CA2+ (COMPONENTS OF SYNTHESIS OF HAP) ARE LIBERATED TO FORM CA5(PO4)3(OH)
6. ) DEPOSITION OF HAP PROCEEDS ONTO CACO3 CRYSTALS

Question 25

A DIET RICH IN...

Answer 25

PROTEIN, VITAMIN C/D/A, CALCIUM, PHOSPHORUS, MAGNESIUM, AND MANGANESE IS REQUIRED FOR BONE DEPOSITION

Question 26

(1) OSTEOID SEAM AND (2) CALCIFICATION FRONT

Answer 26

1. ) UNMINERALIZED BAND OF BONE MATRIX | 2. ) BETWEEN THE OSTEOID SEAM AND THE OLD MINERALIZED BONE

Question 27

BONE GROWTH CESSATION

Answer 27

AT AGE... 21 FOR MALES 18 FOR FEMALES

Question 28

HORMONAL CONTROL OF BONE AND CALCIUM HOMEOSTASIS

Answer 28

1. ) PARATHYROID HORMONE - (PTH) INCREASES THE NUMBER AND ACTIVITY OF OSTEOCLASTS, PROMOTES RECOVERY OF CALCIUM FROM URINE AND PROMOTES FORMATION OF CALCITRIOL (PART OF PARAFOLLICULAR TISSUE - CELLS IN THE THYROID OUTSIDE OF THE FOLLICULAR GLAND) 2. ) CALCITONIN - INHIBITS ACTIVITY OF OSTEOCLASTS, SPEEDS UP CALCIUM ABSORPTION FROM BLOOD AND ACCELERATES CALCIUM DEPOSITION BY BONES 3. ) VITAMIN D - CALCIUM AND PHOSPHATE ABSORPTION AND REABSORPTION, SIMILAR STRUCTURE TO ANDROGEN AND ESTROGEN

Question 29

VITAMIN D

Answer 29

ACTIVATED BY THE RUPTURE OF THE BETA RING BY UV LIGHT FROM THE SUN ONCE ACTIVATE THE MOLECULE IS MOVED TO THE LIVER, TRANSFORMED AND MOVED TO THE KIDNEY WHERE IT IS OFFICIALLY ACTIVATED AND ALLOWED TO ACT ON VARIOUS TISSUES INTESTINES - INCREASES DIET CALCIUM AND PHOSPHATE ABSORPTION KIDNEYS - DECREASES CALCIUM LOSS IN THE URINE BONE - INCREASES CALCIUM MOBILIZATION FROM THE BONE

Question 30

VITAMIN D ENDOCRINE ACTIONS

Answer 30

``` INTESTINAL CALCIUM TRANSPORT BONE METABOLISM RENAL CALCIUM ABSORPTION BLOOD PRESSURE INSULIN SECRETION ```

Question 31

VITAMIN D AUTOCRINE/PARACRINE ACTIONS

Answer 31

INHIBITION OF CELL PROLIFERATION PROMOTION OF CELL DIFFERENTIATION IMMUNE REGULATION

Question 32

PTH BALANCE

Answer 32

INCREASED PTH INHIBITS RELEASE FROM OSTEOBLASTS/STROMAL CELLS OF OPG THAT INHIBITS OSTEOCLASTS INCREASE PTH => INCREASED RANKL AND DECREASED OPG => INCREASED OSTEOCLASTS => INCREASED CALCIUM IN THE BLOOD

Question 33

HORMONAL REGULATION OF CALCIUM

Answer 33

RISING CALCIUM LEVELS TRIGGER THYROID TO RELEASE CALCITONIN (INHIBITS BONE RESORPTION AND STIMULATES CALCIUM SALTS TO BE DEPOSITED IN THE BONE) FALLING CALCIUM LEVELS SIGNAL PTG TO RELEASE PTH (SIGNALS OSTEOCLASTS TO DEGRADE BONE MATRIX AND RELEASE CALCIUM INTO THE BLOOD)

Question 34

BONE COMPOSITION

Answer 34

60% INORGANIC MATERIAL - FORMED FROM HAP 25% ORGANIC MATERIAL - COMPOSED OF TYPE I COLLAGEN AND GF 15% WATER

Question 35

BONE REMODELING CYCLES

Answer 35

COUPLED AND BALANCED - OSTEOCLAST ACTIVITY = OSTEOBLAST ACTIVITY COUPLED AND UNBALANCED - OSTEOCLAST ACTIVITY > OSTEOBLAST ACTIVITY UNCOUPLED - OSTEOCLAST ACTIVITY >> OSTEOBLAST ACTIVITY

Question 36

MECHANICAL STRESS ON BONE

Answer 36

INCREASES OSTEOBLAST ACTIVITY

Question 37

OSTEOPOROSIS

Answer 37

BONES BECOME FRAGILE AND MORE LIKELY TO FRACTURE, BONE LOSES DENSITY (I.E. CALCIUM AND MINERALS IN THE BONE)