Metabolic Bone disease

Question 1

Metabolic bone disease

Answer 1

diseases in bone remodeling

- replacing bone with new bone (~every 7-10 years)

Question 2

When does osteoid calcify?

Answer 2

at a low calcium phosphate product

Ca x PO4 >24

Question 3

Osteoblast secrete _____, which binds to osteoclasts and stimulate bone resorption into blood. It competes with ____ to bind to the RANK receptor.

Answer 3

RANKL

OPG

Question 4

BOne signaling pathway that makes bone, and a pathway that inhibits it

Answer 4

Wnt Frizzled/LRP-5 B-catenin
- parallels RANKL

inhibited by sclerostin

Question 5

Osteoporosis

Answer 5

compromised bone strength

- predisposing to increased risk of fragility fractures

Question 6

3 classic fragility fractures due to osteoporosis

Answer 6

1. spine
2. hip
3. wrist

• if pt has fragility fracture, in absence of another dx, it defines osteoporosis

Question 7

Risk factors for fragility fractures (osteopor)

Answer 7

1. age > 50
2. falls
3. low bone mass
4. previous fractures

Question 8

Prevention and treatment of osteoporosis

Answer 8

1. calcium 1000-1500 mg/day
2. VIt D:
   1000 units/d
3. Exercise
   - aerobic + resistance
4. Falls
   - assess and prev.

Question 9

Which impaired bone mineralization is in adults and which in kids?

Answer 9

adults: osteomalacia
children: rickets

= soft, weak bones

Question 10

Congenital hypophosphatemic rickets (Vit D resistant rickets) will present with what?

Answer 10

1. Renal phosphate wasting
   - low serum PO4
2. Impaired 1,25 (OH)2 Vit D form
   - low serum PO4 and Ca
   (cant mineralize bone)

Question 11

Radiology of osteomalacia vs Rickets

Answer 11

Osteomalacia
- Fractures
- Pseudofractures
(milkmans, looser’s lines)

Rickets
- bowing of long bones
- flaring ends of long bones
(no fractures)

Question 12

Paget’s disease of bone

Answer 12

idiopathic bone condition (but not truly)

Characterized by excessive/unregulated bone resorption and formation
- bone is larger and weaker

Question 13

Etiology of paget’s disease (not truely idiopathic)

Answer 13

Genetic predisposition

Chronic paramyxovirus infxn

Question 14

Evidence for Paget’s disease is a result of a genetic disorder

Answer 14

1. mutation of osteoprotegerin gene
2. 18q linkage
3. mutation of Sequestosome
4. familial aggregation

Question 15

SequestosomeI (SQSTMI)

Answer 15

ubiquitin binding protein
- forms ubiq chains that fxn as protein scaffolds for IL-1 and TNF induced NF-KB activation
–>
regulates RANK signaling that controls osteoclast differentiation, activity, and survival.

• mut of SQSTM1 = linked to pagets disease
• enhances osteoclast formation/reactivity

Question 16

How are genetic components and paramyxovirus infxns linked to pagets disease?

Answer 16

Genetic:
Enhances osteoclast formation/reactivity

Paramyxovirus infxn:
Induces changes in osteoclast precursors

Question 17

Common bone sites of involvement in pagets disease

Answer 17

1. pelvis
2. skull
3. vertebrae
4. femur
5. tibia

• highly vascular (hypervascular) bone

Question 18

Cardiovascular features of pagets disease

Answer 18

1. atherosclerosis
2. aortic stenosis
3. CHF (high output)

Question 19

Neurological features of Pagets disease

Answer 19

1. Deafness (8th n, ossicles)
2. CN compression
3. Spinal cord compression

Question 20

Triphasic clinical course of pagets disease

Answer 20

Osteoclastic –>
osteoclastic + osteoblastic –>
osteoblastic

(can see elevated ALK phos in 2nd phase, by 3rd phase, may or may not see elevated alk phos due to both resorption and formation dying off)
* will see intense bone formation in osteoblastic phase