MSK L15 Osteoporosis

Question 1

Bone structure:

Answer 1

1. Cortical bone → compact outershel (bone strength)
2. Trabecular bone → network of interconnecting plates →
   a. Strength
   b. Surface for exchange of calcium
   c. Physical template for haemopoiesis

Question 2

Macroarchitecture and bone strength:

Answer 2

1. Bone strength
   a. Cross sectional area → large resistance ot bending
   b. Cortical thickness
2. Bone shape
   a. Hip axis length →

Question 3

Microarchitecture and bone strength

Answer 3

Trabecular bone:
1.	Trabecular thickness
2.	Trabecular number
3.	Trabecular connectivity
Cortical bone
1.	Cortical thickness
2.	Cortical porosity

Question 4

Connectedness of trabeculae → Eular

Answer 4

Eular Buckling Theory

See image 112 – organisatino of plates important in strength

Question 5

Fibrils →

Answer 5

→ hydroxyapatitie crystals – resistance to compression

Question 6

Organic phase →

Answer 6

type 1 collagen and other non-collagenous proteins e.g. osteocalcin → tensile strength

Question 7

Section 2: Bone remodelling

Answer 7

1. Lifelong process involving discrete sites throughout the while skeleton
2. Each remodelling cycle takes 3-4 months to complete
3. Ensures readily available supply of calcium for calcium homeostasis
4. Maintains bone integrity by replacing sites of fatigue damage

Question 8

Bone Formation

Answer 8

1. Mechanical Loading
2. Androgens
3. Intermittent PTH
4. B-blockers

Question 9

Bone resorption

Answer 9

1. Oestrogen defiency
2. Immobilization
   Low Ca

Question 10

Osteoblasts action

Answer 10

→ Pump protons that activated enzymes → TRAP and CATK

Question 11

Osteoclasts Formed from

Answer 11

mononucleur precursors shared with monocytes then a number of factors drive the mononuclear precursors down osteoclast pathway.

Question 12

Osteoclasts Stimulation of formation

Answer 12

Cytokines → RANKL (produced by stromal cells in bone marrow) interact with RANK receptor = stimulation and formation of mature osteoclasts.

Question 13

OPG →

Answer 13

Block RANKL

Question 14

Denosumab →

Answer 14

RANK ligand inhibitor for postmenopausal women = osteoporosis treatment

Question 15

Osteoblasts: Found

Answer 15

Sit on the surface of trabecular bone synthesis

Question 16

Osteoblasts:Mesenchyme precursor →

Answer 16

Produce myoblasts (muscle), adipocytes(fat) chondrocytes(cartilage) and osteoblasts (bone).

Question 17

Osteoblasts: LRP5/Wnt signlaiing pathway

Answer 17

Stimulates osteoblasts formation

Question 18

Osteoblasts: A mutation in LRP5

Answer 18

Constant activation of pathway → excess bone density in hip and spine

Question 19

Osteoblasts: Sclerostin

Answer 19

Secreted by osteocytes, which inhibits bone formation. Strain on bone switches this off.

Question 20

Osteoblasts:Sclerostin defiency

Answer 20

Causes a high bone mass phenotype
• Enlarged mandibles
• Facial nerve palsys due to overgrowth of skull in IAM

Question 21

Sclerostin antibody

Answer 21

Osteoporosis treatment

Question 22

Epi

osteoporosis

Answer 22

More common in women

Fractures most common with age and in hip, vertebrae, colles’ (distal radius)

Question 23

Bone remodelling in osteoporosis

Answer 23

Imbalance – amount of resorption exceeds formation

Oestrogen related

Question 24

Osteoporosis measure in

Answer 24

DXA

Question 25

Peak bone mass

Answer 25

Diet Exercise Genes

Question 26

Bone loss

Answer 26

``` Low calcium/vitamin d Immobility Genes Estrogen defiency Steroids ```

Question 27

Vertebral Fracture

Answer 27

1. Kyphoctic deformity 2. Height loss 3. Increased backpain 4. Decreased activity 5. Impaired quality of life 6. Increased mortality 7. Increased risk of vertebral and non-vertebral fractures

Question 28

Bone remodelling and osteoporosis: Trabecular Bone:

Answer 28

1. Increased activation frequency 2. Increased erosion depth 3. Reduced trabecular thickenss

Question 29

Bone remodelling and osteoporosis: Cortical Bone

Answer 29

Structural changes also effect cortical bone, characterised by endosteal expansion, cortical thinning, and an increase in size and number of Haversian canals. Expansino of endosteal surface, thinning and weakening

Question 30

Treatments:

Answer 30

Anti-resorptive Mixed action Anabolic

Question 31

Anti-resorptive

Answer 31

Bisphosphonates → alendronate, risedronate, Ibandronate Denosumab → RANK ligand inhibitor for postmenopausal women = osteoporosis treatment → more potnet thatn aldrenodate (knocks out osteoclast)

Question 32

Mixed action

Answer 32

Strontium → act as a combination of stimulating osteobalsta and inhibiting osteoclasts

Question 33

Anabolic

Answer 33

PTH → teriparatide (PTH1-34), Preotact (PTH 1-84)

Question 34

Bisphosphonates → Treatment for

Answer 34

1. Osteoporosis 2. Pagets → a particular sites in skeleton get overgrowth of osteoglasts = expansion of bone and bone pain 3. Hypercalcaemia malignancy → secondary depositis in skeleton → stimulatin of osteoclasts, resorption and hypercalcaemia.

Question 35

Bisphosphonates → Chemical structure

Answer 35

Retained in bone as they bind in bone as they bind the crystals

Question 36

Strontium ranelate →

Answer 36

heavily metal salt that is retained within bone, which stimulates formation and inhibits resorption