MSK L15 Osteoporosis Flashcards Preview

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Flashcards in MSK L15 Osteoporosis Deck (36)
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1
Q

Bone structure:

A
  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
Q

Macroarchitecture and bone strength:

A
  1. Bone strength
    a. Cross sectional area → large resistance ot bending
    b. Cortical thickness
  2. Bone shape
    a. Hip axis length →
3
Q

Microarchitecture and bone strength

A
Trabecular bone:
1.	Trabecular thickness
2.	Trabecular number
3.	Trabecular connectivity
Cortical bone
1.	Cortical thickness
2.	Cortical porosity
4
Q

Connectedness of trabeculae → Eular

A

Eular Buckling Theory

See image 112 – organisatino of plates important in strength

5
Q

Fibrils →

A

→ hydroxyapatitie crystals – resistance to compression

6
Q

Organic phase →

A

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

7
Q

Section 2: Bone remodelling

A
  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
Q

Bone Formation

A
  1. Mechanical Loading
  2. Androgens
  3. Intermittent PTH
  4. B-blockers
9
Q

Bone resorption

A
  1. Oestrogen defiency
  2. Immobilization
    Low Ca
10
Q

Osteoblasts action

A

→ Pump protons that activated enzymes → TRAP and CATK

11
Q

Osteoclasts Formed from

A

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

12
Q

Osteoclasts Stimulation of formation

A

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

13
Q

OPG →

A

Block RANKL

14
Q

Denosumab →

A

RANK ligand inhibitor for postmenopausal women = osteoporosis treatment

15
Q

Osteoblasts: Found

A

Sit on the surface of trabecular bone synthesis

16
Q

Osteoblasts:Mesenchyme precursor →

A

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

17
Q

Osteoblasts: LRP5/Wnt signlaiing pathway

A

Stimulates osteoblasts formation

18
Q

Osteoblasts: A mutation in LRP5

A

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

19
Q

Osteoblasts: Sclerostin

A

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

20
Q

Osteoblasts:Sclerostin defiency

A

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

21
Q

Sclerostin antibody

A

Osteoporosis treatment

22
Q

Epi

osteoporosis

A

More common in women

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

23
Q

Bone remodelling in osteoporosis

A

Imbalance – amount of resorption exceeds formation

Oestrogen related

24
Q

Osteoporosis measure in

A

DXA

25
Q

Peak bone mass

A

Diet
Exercise
Genes

26
Q

Bone loss

A
Low calcium/vitamin d
Immobility
Genes
Estrogen defiency
Steroids
27
Q

Vertebral Fracture

A
  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
Q

Bone remodelling and osteoporosis: Trabecular Bone:

A
  1. Increased activation frequency
  2. Increased erosion depth
  3. Reduced trabecular thickenss
29
Q

Bone remodelling and osteoporosis: Cortical Bone

A

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
Q

Treatments:

A

Anti-resorptive
Mixed action
Anabolic

31
Q

Anti-resorptive

A

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

32
Q

Mixed action

A

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

33
Q

Anabolic

A

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

34
Q

Bisphosphonates → Treatment for

A
  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
Q

Bisphosphonates → Chemical structure

A

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

36
Q

Strontium ranelate →

A

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

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