Patho-2-Osteoporosis Flashcards Preview

Block 6 - MSK > Patho-2-Osteoporosis > Flashcards

Flashcards in Patho-2-Osteoporosis Deck (42):
1

Osteoporosis

fragility of bone that causes increase risk of fractures

2

WHO classification of osteoporosis

BMD T score o f> -2.5

3

Osteopenia

BMD is lower than normal but enough to be classified as osteoporosis

  • bone matrix normally mineralised but there's less bone

4

Osteomalacia

insufficient Ca2+ & phosphate to mineralise newly formed osteoid

  • bone = softer & liable to bend, deform or fracture

5

Types of Osteoporosis

  • Generalised - primary or secondary (unassociated or associated with other diseases respectively)
  • Regional

6

Generalised Osteoporosis unassociated with other diseases

  • post-menopausal
  • ageing

7

Generalised osteoporosis associated with other diseases

Inflammatory arthritis - RA

Environmental:

  • calcium deficiency
  • alcohol
  • drug induced - corticosteroids, heparin

Endocrine causes

  • hyper-parathyroidism
  • Cushing's syndrome
  • Hyper-thyroidism
  • Hypogonadism
  • Anorexia nervosa
  • Exercise induced amenorrhea

8

Diagnosis of Osteoporosis

defined in relation to degree to which bone mineral density is reduced

  • T-score (no. of standard deviations from young normal mean)
    • useful for dx
  • Z-score (no. of SD from age-matched mean)
    • useful to determine if 2ndry cause exists for OP

Osteoporosis = T score below -2.5

9

BMD sites

Spine (L1-4 or L2-4)

  • predicts spine fracture
  • trabecular bone

Hip (femoral neck, intertrochanter, trochanteric)

  • predictive of # risk hip & spine
  • cortical bone

10

BMD Advantages & Disadvantages

Advantages:

  • quick & easy
  • minimal radiaiton exposure
  • WHO classification based on DEXA

Disadvantages:

  • mineral content across specific area not taking depth into consideration 
  • doesn't give full assessment of bone strength (microarchitecture, bone turnover)
  • vary between instruments

11

FRAX Tool - WHO Fracture Risk Assessment Tool

determines clinical risk factors & BMD at femoral neck

  • algorithm indicates 10yr probabily of #
  • computer driven

12

Normal bone development continues until...

35yrs

13

After you reach peak bone mass....

bone density starts to decline

14

Peak bone mass depends on?

  • genetic & envrionmental factors
  • accrued through intra-uterine growth, childhood, puberty

 

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15

Describe the bone remodelling process

  • Quiescene (lining cells)
  • Resorption (osteoclasts)
  • resorption cavity
  • formation (osteblasts)
  • new bone formation

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16

Remodelling in trabecular bone osteoporosis

  • resporption cavities more frequent & deeper in osteoporitic bone - perforations occur
  • resorption cavities are incompletey replaced by new bone

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17

Remodelling imbalance is due to?

progressive loss of trabecular bone due to increased osteoclastogenesis

18

Normal Osteoclastogenesis

  • RANKL made by osteoblasts binds to RANK on surface of osteoclast precursors & recruits adaptor protein TRAF6 --> NFKB activation & translocation to nucleus
  • NFKB increases c-Fos expression which c-Fos interacts with NFATc1 to trigger transcription of osteoclastogenic genes 
  • OPG inhibits initiation of proces by binding to RANKL

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19

Function of OPG

Inhibits the number of osteoclast by inhibiting differentiation of osteoclast precursors

20

Effect of Oestrogen on osteoclastogenesis

Anti-resorptive effect by stimulating OPG expression in OB

21

Osteoblast regulation

  • LRP5 = modulator of OB function
  • co-receptor series of OB stimulating proteins via Wnt signalling pathway
  • Frz & LRP5 bind to Wnt --> activating bone formation
  • inhibitory effects of glucocorticosteroids may be via Wnt signalling pathway

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22

Prevention of OP

  • calcium intake (800-1200mg/day)
  • exercise
  • avoid smoking & alcohol
  • Vit D intake

23

Pharmacological Mx of OP

  • Anti-resorptives
  • Anabolic agents
  • Dual agents

24

Examples of anti-resorptives

  • Bisphosphates
  • SERMS
  • Calcitol
  • RANKL inhibitor

25

Examples of anabolic agents

PTH

26

Example of dual agents

Strontium ralenate

27

What is the requirement to be included to OP management regimen?

Tx needs to demonstrate:

  • increase in bone density
  • reduction in # sites

28

MOA of bisphosphates

Encourage osteoclast to undergo apoptosis

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29

MOA of denosumab

inhibits maturation of osteoclast by binding to & inhibiting RANKL

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30

Function of RANKL

promotes maturation of osteoclasts

31

Effectiveness of Oestrogen

Risk of breast cancer significant so not advised for OP treatment any more

32

SERM

Selective Estrogen Receptor Modulator

33

MOA of SERM

Acts on estrogen receptors in bone and not in breast tissue

34

MOA of calcitrol

  • Regulates calcium homeostasis and bone metabolism 
  • Promotes bone mineralisation

35

MOA of parathyroid hormone

increases serum calcium --> increases bone resorption

36

MOA of Strontium Ralenate

  • Increases bone formation and decreases bone remodelling. 
  • Induces pre-osteoblasts & osteoblast differentiation 
  • inhibits osteoclast differentiation

37

Choice of Rx for Post-menopausal women

  • Bisphosphates and denosumab
  • 2nd line: Strontium

38

Choice of Rx for Male OP

  • Bisphosphates 
  • 2nd line: Strontium

39

Choice of Rx for Corticosteroid induced OP

Bisphosphates

40

Choice of Rx for prevention of fracture

Bisphosphates and denosumab

41

How is Osteoporosis diagnosed?
1. When a fracture occurs after fall down stairs
2. When the patient has a family history of osteoporosis
3. When Bone density is below -3.0
4. When a facture occurs after minimal trauma
5. If Vitamin D is low

3. When Bone density is below -3.0

42

Treatment of established osteoporosis
1.Requires Hydrotherapy to improve bone density
2. Needs Medicare approval
3. Calcium supplement is adequate
4. Anabolic Agents are always needed to build bone is osteoporosis
5. Antiresorptiveagents are first line therapy

5. Antiresorptiveagents are first line therapy