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

Patho-2-Osteoporosis Flashcards

1
Q

Osteoporosis

A

fragility of bone that causes increase risk of fractures

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2
Q

WHO classification of osteoporosis

A

BMD T score o f> -2.5

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3
Q

Osteopenia

A

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

  • bone matrix normally mineralised but there’s less bone
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4
Q

Osteomalacia

A

insufficient Ca2+ & phosphate to mineralise newly formed osteoid

  • bone = softer & liable to bend, deform or fracture
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5
Q

Types of Osteoporosis

A
  • Generalised - primary or secondary (unassociated or associated with other diseases respectively)
  • Regional
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6
Q

Generalised Osteoporosis unassociated with other diseases

A
  • post-menopausal
  • ageing
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7
Q

Generalised osteoporosis associated with other diseases

A

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
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8
Q

Diagnosis of Osteoporosis

A

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

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9
Q

BMD sites

A

Spine (L1-4 or L2-4)

  • predicts spine fracture
  • trabecular bone

Hip (femoral neck, intertrochanter, trochanteric)

  • predictive of # risk hip & spine
  • cortical bone
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10
Q

BMD Advantages & Disadvantages

A

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
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11
Q

FRAX Tool - WHO Fracture Risk Assessment Tool

A

determines clinical risk factors & BMD at femoral neck

  • algorithm indicates 10yr probabily of #
  • computer driven
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12
Q

Normal bone development continues until…

A

35yrs

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13
Q

After you reach peak bone mass….

A

bone density starts to decline

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14
Q

Peak bone mass depends on?

A
  • genetic & envrionmental factors
  • accrued through intra-uterine growth, childhood, puberty
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15
Q

Describe the bone remodelling process

A
  • Quiescene (lining cells)
  • Resorption (osteoclasts)
  • resorption cavity
  • formation (osteblasts)
  • new bone formation
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16
Q

Remodelling in trabecular bone osteoporosis

A
  • resporption cavities more frequent & deeper in osteoporitic bone - perforations occur
  • resorption cavities are incompletey replaced by new bone
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17
Q

Remodelling imbalance is due to?

A

progressive loss of trabecular bone due to increased osteoclastogenesis

18
Q

Normal Osteoclastogenesis

A
  • 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
19
Q

Function of OPG

A

Inhibits the number of osteoclast by inhibiting differentiation of osteoclast precursors

20
Q

Effect of Oestrogen on osteoclastogenesis

A

Anti-resorptive effect by stimulating OPG expression in OB

21
Q

Osteoblast regulation

A
  • 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
22
Q

Prevention of OP

A
  • calcium intake (800-1200mg/day)
  • exercise
  • avoid smoking & alcohol
  • Vit D intake
23
Q

Pharmacological Mx of OP

A
  • Anti-resorptives
  • Anabolic agents
  • Dual agents
24
Q

Examples of anti-resorptives

A
  • Bisphosphates
  • SERMS
  • Calcitol
  • RANKL inhibitor
25
Q

Examples of anabolic agents

A

PTH

26
Q

Example of dual agents

A

Strontium ralenate

27
Q

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

A

Tx needs to demonstrate:

  • increase in bone density
  • reduction in # sites
28
Q

MOA of bisphosphates

A

Encourage osteoclast to undergo apoptosis

29
Q

MOA of denosumab

A

inhibits maturation of osteoclast by binding to & inhibiting RANKL

30
Q

Function of RANKL

A

promotes maturation of osteoclasts

31
Q

Effectiveness of Oestrogen

A

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

32
Q

SERM

A

Selective Estrogen Receptor Modulator

33
Q

MOA of SERM

A

Acts on estrogen receptors in bone and not in breast tissue

34
Q

MOA of calcitrol

A
  • Regulates calcium homeostasis and bone metabolism
  • Promotes bone mineralisation
35
Q

MOA of parathyroid hormone

A

increases serum calcium –> increases bone resorption

36
Q

MOA of Strontium Ralenate

A
  • Increases bone formation and decreases bone remodelling.
  • Induces pre-osteoblasts & osteoblast differentiation
  • inhibits osteoclast differentiation
37
Q

Choice of Rx for Post-menopausal women

A
  • Bisphosphates and denosumab
  • 2nd line: Strontium
38
Q

Choice of Rx for Male OP

A
  • Bisphosphates
  • 2nd line: Strontium
39
Q

Choice of Rx for Corticosteroid induced OP

A

Bisphosphates

40
Q

Choice of Rx for prevention of fracture

A

Bisphosphates and denosumab

41
Q

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
A
  1. When Bone density is below -3.0
42
Q

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
A
  1. Antiresorptiveagents are first line therapy

Block 6 - MSK (5 decks)

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