MSK L15 Osteoporosis Flashcards Preview

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Flashcards in MSK L15 Osteoporosis Deck (36):
1

Bone structure:

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

2

Macroarchitecture and bone strength:

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

3

Microarchitecture and bone strength

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

4

Connectedness of trabeculae → Eular

Eular Buckling Theory
See image 112 – organisatino of plates important in strength

5

Fibrils →

→ hydroxyapatitie crystals – resistance to compression

6

Organic phase →

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

7

Section 2: Bone remodelling

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

8

Bone Formation


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

9

Bone resorption

1. Oestrogen defiency
2. Immobilization
Low Ca

10

Osteoblasts action

→ Pump protons that activated enzymes → TRAP and CATK

11

Osteoclasts Formed from

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

12

Osteoclasts Stimulation of formation

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

13

OPG →

Block RANKL

14

Denosumab →

RANK ligand inhibitor for postmenopausal women = osteoporosis treatment

15

Osteoblasts: Found

Sit on the surface of trabecular bone synthesis

16

Osteoblasts:Mesenchyme precursor →

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

17

Osteoblasts: LRP5/Wnt signlaiing pathway

Stimulates osteoblasts formation

18

Osteoblasts: A mutation in LRP5

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

19

Osteoblasts: Sclerostin

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

20

Osteoblasts:Sclerostin defiency

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

21

Sclerostin antibody

Osteoporosis treatment

22

Epi

osteoporosis

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

23

Bone remodelling in osteoporosis

Imbalance – amount of resorption exceeds formation
Oestrogen related

24

Osteoporosis measure in

DXA

25

Peak bone mass

Diet
Exercise
Genes

26

Bone loss

Low calcium/vitamin d
Immobility
Genes
Estrogen defiency
Steroids

27

Vertebral Fracture




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

28

Bone remodelling and osteoporosis: Trabecular Bone:

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

29

Bone remodelling and osteoporosis: Cortical Bone

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

30

Treatments:

Anti-resorptive
Mixed action
Anabolic

31

Anti-resorptive



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

32

Mixed action

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

33

Anabolic

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

34

Bisphosphonates → Treatment for


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.

35

Bisphosphonates → Chemical structure

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

36

Strontium ranelate →

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

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