Bone Physiology

Question 1

______ is dense and used for support

Answer 1

Compact bone

Question 2

____ or ____ forms a calcified lattice

Answer 2

spongy bone or trabecular bone

Question 3

What is the primary responsibility of bone?

Answer 3

to develop and maintain mass and architecture sufficient to carry functional loads without fracture.

Question 4

______: occurs when resorption precedes formation

Answer 4

re-modeling (structure present, then taken down, then remodeled)

Question 5

4 stages of bone re-modeling

Answer 5

1)quiescence
osteoclasts: recruitment, differentiation, activation
2)resorption
osteoblasts: recruitment, proliferation
osteoclasts: apoptosis, removal
3)reversal
matrix synthesis
4)formation
mineralization

Question 6

_______ are unique bone resorbing cells of the monocyte-macrophage lineage

Answer 6

osteoclasts

Question 7

characteristics of osteoclasts:
nucleus - _______
activated by - ______

Answer 7

multinucleated

receptor activator of nf kappa b ligand (RANKL)

Question 8

Osteoclasts:

polarization facilitates _____, _______, and _____

Answer 8

clear zone, ruffled border formation, and bone resorption

Question 9

disease in which osteoclasts are unable to resorb bone. What is the shape seen on X-ray?

Answer 9

Osteopetrosis

erlenmeyer flask appearance

Question 10

bone remodeling is accelerated with _______

Answer 10

age

Question 11

Name some other scenarios in which osteoclasts would be more active than osteoblasts

Answer 11

low testosterone
low estrogen
low systemic calcium levels

Question 12

osteoblasts come from what progenitor cell?

Answer 12

mesenchymal cells

Question 13

mesenchymal cells can differentiate into which cells?

what is the determining factor?

Answer 13

chondrocytes, myoblasts, adipocytes, and tendon cells

TRANSCRIPTION FACTORS

Question 14

osteoblasts make ______, express the ______ receptor, also produce ____ and ____ (ECM proteins),

Answer 14

type I collagen, EXPRESS PARATHYROID HORMONE RECEPTOR, osteocalcin and bone sialoprotein

Question 15

osteoblast transcription factor: ______

Answer 15

Runx2, (Runx2 -/-mice don’t make bone)

Question 16

______ have osteoblast phenotype

Answer 16

osteocytes

Question 17

Sclerostin is made in _____, blocks _____, and inhibits _____.

Answer 17

osteocytes, Wnt signaling, bone formation.

Question 18

disease associated with sclerostin?

Answer 18

osteosclerosis (sclerostin always missing)

Question 19

_________ molecules are a fundamental control of bone remodeling.

Answer 19

Wnt signaling molecules

Question 20

Name two ways to increase bone formation.

Answer 20

• ab to RANKL would decrease the availability of RANKL to bind osteoblasts and activate osteoclasts, and would increase bone mass.
• Ab that inhibits sclerostin would unblock Wnt signaling and lead to increased bone formation.

Question 21

______ are the most abundant cell type in bone

Answer 21

osteocytes

Question 22

osteocytes are ______ in origin

Answer 22

mesenchymal

Question 23

bone formation inhibitor associated with osteocytes?

Answer 23

sclerostin

Question 24

sclerostin plays a role in both ____ and ____

Answer 24

bone modeling and bone remodeling

Question 25

Name some diseases of altered calcium homeostasis and bone metabolism.

Answer 25

osteoporosis
osteopetrosis
osteosclerosis
cancer
diabetes, cardiovascular disease, treatment side-effects

Question 26

decrease in _____ is associated with increased Fracture risk

Answer 26

bone mineral density (BMD)

Question 27

mortality rate associated with hip fractures

Answer 27

24%

Question 28

________ inhibit bone resorption by inhibiting farnesyl synthase and preventing formation of __________

Answer 28

bisphosphonates

ruffled border

Question 29

bisphosphonates reverse _____ and decrease ____

Answer 29

bone loss

bone turnover

Question 30

two treatments for osteoporosis?

Answer 30

bisphosphonates and blocking RANKL

Question 31

Current treatment used to block RANKL?

Answer 31

Xgeva, used to block downstream differentiated products, blocking eventual formation of osteoclasts (WITHOUT INTERFERING WITH PROGENITOR CELL)

Question 32

a bone disease that makes bones abnormally dense and prone to fracture. Associated with diminished OSTEOCLAST function. Characterized by skeletal fragility.

Answer 32

osteopetrosis

Question 33

a bone disease of abnormal hardening of bone and an elevation in density. Associated with increased OSTEOBLAST function. Characterized by increased bone mass.

Answer 33

osteosclerosis

Question 34

______ ______ is associated with hypercalcemia, nerve compression, bone pain, and fracture.

Answer 34

bone metastasis

Question 35

bone metastasis is facilitated by the activity of ______

Answer 35

osteoclasts (intravasation, homing and survival, extravasation)

Question 36

Therapeutic targets blocking steroid-dependent tumor cell proliferation

Answer 36

androgen and estrogens via aromatase inhibitors

Question 37

treatments for cancer can cause ___ and ____

Answer 37

osteopenia and osteoporosis

Question 38

how does type 2 diabetes increase risk of bone fracture?

Answer 38

• hyperglycemia and hypercalciuria lead to low bone turnover.
• hyperinsulinemia, hyperglycemia, treatment with TZD, low vitamins (D) leads to lone bone quality.
• concomitant meds, cataracts, peripheral neuropathy, retinopathy, ulcers, hypoglycemia, nocturia can all increase the risk of falls

Question 39

correlation between cardiovascular disease and PTH?

Answer 39

increased risk of vascular disease over time with high levels of PTH

Question 40

bone fractures are a major risk factor with significant morbidity and mortality with which age group?

Answer 40

ANY AGE GROUP!!!!

Question 41

DISEASE: the skeleton plays a central role in _____, _____, and ____

Answer 41

disease development, response to treatment, and quality of life.