Basic science

Question 0

Which are nitrogen containing bisphosphonates?

Answer 0

N2 - Risedronate (PO) & Zolendronate (IV)

Non-N2 - Alendronate (PO) & Pamidronate (IV)

Changed pyrophosphate from POP to PCP

2 side chains
R1 - bone affinity
R2 - anti-resorption capacity

Question 1

What is the Heuter-Volkman principle

Answer 1

Increased compression forces across physis leads to decreased longitudinal physeal growth

Delpech principle is that increased tension forces across physis increases longitudinal physeal growth

Question 2

3 modes of action of bisphosphonates

Answer 2

1. Bind HA inhibiting OC resorption
2. Interfere with OC metabolism - kerbs cycle
3. Induce apoptosis of OC

Question 3

What is tumoral calcinosis?

Answer 3

Rare condition of calcification of extra-articular soft tissues around joints associated with normal Ca and elevated Phosphate levels

Typically affects hips, shoulders and elbows
Kids and young adults

Question 4

Causes of osteonecrosis

Answer 4

Idiopathic
Corticosteroids
Alcohol
Trauma
Systemic disorders
Haemoglobinopathies 
Storage - gauchers
Caisson
Radiation

Question 5

What are the characteristics of and genetics of Leri-Weil dyschondrosteosis?

Answer 5

Short stature and bilateral Madelungs
SHOX gene
Sex linked dominant
On either x or Y chromosomes.

Question 6

Genetics of Cleidocranial dysplasia

Answer 6

Autosomal dominant defect in CBFA-1

Transcriptional factor activatin osteoblast differentiation

Question 7

Genetics of Ellis van Creveld

Answer 7

Autosomal recessive EVC gene

Acromesomelic shortening and post axial polydactyly amongst other anomalies

Question 8

What is caused by mutations of -

a) FGFR-2
b) CBFA-1
c) Gs Alpha protein
d) FBGFR-3

Answer 8

a) Apert’s
b) cleidocranial dysplasia
c) fibrous dysplasia
d) achondroplasia

Question 9

What diseases are associated with defects in 
A) elastin
B) Fibrillin
C) type 1 collagen
D) Type 2 collagen

Answer 9

A) SVAS and AD cutis lads
B) marfan
C) OI & ED
D) SED, achondrogenesis, Stickler syndrome

Question 10

What do Somites develop into and what forms from them?

Answer 10

Mesodermal in origin
Form -
dermatome - Dermis
Myotome - skeletal muscle
Sclerotome - axial skeleton
Neural crest - PNS
Lateral plate mesoderm - dermis
Dorsal myotome - dorsal muscles

Question 11

Action of TGF-Beta and IHH and PTHrP at physis

Answer 11

TGF-B potent inhibitor of maturation, type x collage. Expression and ALP activity.

SMAD-3 increases activity of TGF-B

PTHrP slows maturation of proliferators Chondrocytes.
Indian hedgehog protein stimulates Chondrocytes to produce PTHrP.

Question 12

Northern, western, southern blot, elisa, flow cytometry

Answer 12

Northern - RNA
Southern - DNA
Western - Proteins

ELISA - protein Ag AB
Flow cytometry - DNA bound protein

Question 13

General inheritance patterns and exceptions?

Answer 13

Structural - AD
Enzyme - AR
X-linked recessive - DMD / Becker’s and haemophilia
X-linked dominant rare - hypophosphatEmic tickets and Leei-Weill dyschondrosteosis

Question 14

Prophylaxis for Ho

Answer 14

Indomethacin 25mg TDs 6 weeks

Radiation 800Gy

Question 15

What is cathepsin K?

Answer 15

Protease activated by protons from osteoclasts Degrades the ECM of bone

Question 16

What factors act on osteoclasts?

Answer 16

IL-1 
IL-6
TNF-A
Calcitonin
Colchicine
Gamma interferon

No receptors for PTH, Vit-D

Question 17

What synthesis characterises osteoblasts?

Answer 17

Express ALK Ph
Synthesis collagen 1
Receptors for PTH, Vit-D

Question 18

What happens with low calcium?

Answer 18

PTH secreted.
Converts 25-Vit D to active 1,25

Both act in osteoblasts
OB regulates and increases OCl activity

Increases
Bone resorption
GIT absorption
Renal absorption.

Question 19

What is secreted when Ca high?

Answer 19

Calcitonin

Decreases bone resorption

Question 20

What are the different forms of Vit-D?

Answer 20

D3 - skin. Cholecalciferol
D2 - git. Ergo calciferol

25-hydroxycholecalciferol in liver
1,25 in kidney

Active vitamin D acts on gut, kidney and on osteoblasts

Question 21

How does oestrogen affect bone?

Answer 21

Acts on osteoblasts - increase collagen synthesis and ALP activity

Acts on osteoclasts to inhibit function

Question 22

Risk factors for osteoporosis

Answer 22

Non-modifiable
Caucasian, fair hair, scoliosis, OI, early menopause, slender
Modifiable
Inactivity, malnutrition, etoh, smoking, chronic steroids, medications- thyroid, diuretics, phenytoin

Question 23

Causes of osteoporosis

Answer 23

Primary - idiopathic
Secondary - 
Thyroid disease
Hyperparathyroidism 
Hypothalamic hypogonadism 
DM
HIV
Steroids
MM
Immobilisation

Question 24

Lab findings in transient OP

Answer 24

ESR ELEVATED
ALP not.

Hot bone scan and MRI

Question 25

What are the two types of bone formation and where do you find them?

Answer 25

Intramembranous - 
Flat bones (pelvis, clavicle), primary bone healing (absolute stability), distraction osteogenesis, blastem bone (amputation)

Cleidocranial dysplasia - defect in IM Ossif. Mutation of CBFA1 (Runx2) on Chrom 6

Enchondral (form with a cartilagenous anlage)-

Long bone formation embryonic and physeal growth, secondary bone healing (relative stability)

Type x collagen, Sox-9 affecting collagen II, IV, XI and aggrecan.
PTHrP - delays Chondrocyte differentiation in hypertrophic zone