Osteoporosis Flashcards

1
Q

Define osteoporosis.

A

A systemic skeletal disease characterised by low bone mass/density and micro-architectural deterioration.
The patient is at increased risk of bone fragility + fracture.

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2
Q

What is classed as osteroporosis?

A

Defined as bone mineral density (BMD) MORE than 2.5 standard deviations BELOW the young adult mean value (T score < 2.5)

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3
Q

What is osteopenia?

A

Pre-cursor to osteoporosis characterised by low bone density.

  • Defined as BMD between 1-2.5 standard deviations BELOW the young adult mean value (-1< T score < 2.5).
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4
Q

Describe the epidemiology of osteoporosis.

A
  1. 50% of women and 20% of men over 50 are affected.
  2. The incidence increases with age.
  3. Caucasian and Asian races are particularly at risk.
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5
Q

Give some specific risk factors for osteoporosis.
HINT: Mnemonic!

A

S - steroids
H - hyperthyroid, hyperparathyroid
A - alcohol, smoking
T - thin (BMI <22)
T - testosterone decrease
E - early menopause
R - renal/liver failure (less vitamin D activation)
E - erosive/inflammatory bone disease e.g. RA, myeloma
D - diet/diabetes type 1

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6
Q

Name 3 endocrine diseases that can be responsible for causing osteoporosis.

A
  1. Hyperthyroidism and primary hyperparathyroidism: TH and PTH -> increased bone turnover.
  2. Cushing’s syndrome: cortisol leads to increased bone resorption and osteoblast apoptosis.
  3. Early menopause, male hypogonadism: less oestrogen/testosterone to control bone turnover.
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7
Q

What is the affect of high cortisol levels on bone turnover?

A

Cortisol increases bone turnover. It leads to increased bone resorption and it also induces osteoblast apoptosis.

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8
Q

Why can RA cause osteoporosis?

A

RA is an Inflammatory disease. There are high levels of IL-6 and TNF; these are responsible for increased bone resorption.

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9
Q

Give 5 general risk factors for osteoporosis.

A
  1. Old age
  2. Women
  3. FHx of osteoporosis or fracture
  4. Previous bone fracture
  5. Smoking/Alcohol
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10
Q

Why do bones weaken with age?
What part of the bone is affected?

A
  • Changes in trabecular architecture with ageing:
  • Decrease in trabecular thickness - as we age the strain is felt on bones from head to tail, in response, we tend to preferentially preserve:
    VERTICAL TRABECULAE and LOSE HORIZONTAL TRABECULAE
  • Decrease in trabeculae thickness in connections between horizontal trabeculae
    = resulting in decrease trabecular strength and increased susceptibility to fracture
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11
Q

Why are so many women over 50 affected by osteoporosis?

A

Women over 50 are likely to be post-menopausal; they therefore have less oestrogen and so osteoclast action isn’t inhibited. There is a high rate of bone turnover -> bone loss and deterioration -> fracture risk.

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12
Q

Name a hormone that can control osteoclast action and so bone turnover.

A

Oestrogen.

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13
Q

Briefly describe the pathophysiology of osteoporosis.

A
  1. Peak bone mass is at around 25 yrs - then start losing bone mass.
  2. Osteoporosis results from increased bone breakdown by osteoclasts and decreased bone formation by osteoblasts, leading to loss of bone mass.
  3. Bone mass decreases with age, but will depend on the ‘peak’ mass attained in adult life and on the rate of loss in later life.
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14
Q

What 3 factors is bone strength determined by?

A
  1. BDM - bone mineral density (at its peak and the rate of loss)
    - How much mineral in bone
    - Determine by the amount gained during growth and amount lost during ageing
  2. Size
    - Short and fat is stronger than long and thin
    - Distribution of cortical bone
  3. Quality
    - Bone turnover
    - Its architecture of it
    - Mineralisation
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15
Q

Give 3 symptoms of osteoporosis.

A

Only symptoms = fracture.

  1. Thoracic + lumbar vertebral fractures
    - Sudden onset of severe pain in the spine, often radiating to
    the front
    - May lead to kyphosis - ‘widows stoop’
  2. Colles’ fracture of the wrist (distal radius)
    - Typically follow a fall on an outstretched arm
  3. Fractures of the proximal femur
    - Usually occur in older individuals falling on their side or back
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16
Q

What 2 factors are important for determining the likelihood of osteoporotic fracture?

A
  1. Propensity to fall -> trauma.
  2. Bone strength.
17
Q

Investigations for osteoporosis.

A
  1. Bloods:
    * Ca2+, phosphate and alkaline phosphate all normal
  2. X-ray:
    * Demonstrate fractures but insensitive for osteopenia
  3. Dual energy X-ray absorptiometry (DEXA) scan:
    * Low radiation dose and measure important fracture sites (lumbar spine and proximal femur)
    * GOLD STANDARD for measuring bone density and diagnosing
    osteoporosis
    * Generates T scores - see above, more than 2.5 standard deviations = osteoporosis
18
Q

What is the gold standard investigation for osteoporosis?

A

DEXA bone scan.

19
Q

What is a DEXA scan?

A

Dual energy X ray absorptiometry:
-> Measures bone mineral density

20
Q

Name 3 areas of the skeleton commonly affected by osteoporosis that the DEXA scan focuses on.

A
  1. Lumbar spine.
  2. Hip.
  3. Distal radius.
21
Q

What is a T score?

A

A T score is a standard deviation that is compared to a gender-matched young adult mean.

22
Q

What T score signifies that a patient has osteoporosis?

A

T < -2.5

23
Q

What T score signifies that a patient has osteopenia?

A

-2.5 < T < -1

24
Q

What is a normal T score?

A

-1

25
Q

Outline the management of osteoporosis.

A
  1. Lifestyle measures
  2. Pharmacological measures:
    1) Anti-resorptive
    • Bisphosphonates (1st line)
    • Strontium ranelate
    • Denosumab
    • Hormone Replacement Therapy - HRT (oestrogen)
    • Raloxifene
    • Testosterone (for men)
      2) Anabolic
26
Q

Management of osteoporosis: lifestyle measures.

A
  • Quit smoking and reduce alcohol consumption
  • Weight-bearing exercise may increase bone density
  • Calcium and vitamin D rich diet
  • Balance exercises to reduce falls
27
Q

What cells do anti-resorptive treatments target in people with osteoporosis?

A

They decrease osteoclast activity.

28
Q

Give 2 examples of anti-resorptive treatments used in the management of osteoporosis.

A
  1. Bisphosphonates.
  2. HRT.

Anti-resorptive treatments decrease osteoclast activity.

29
Q

What pathway do bisphosphonates target?

A

HMGCoA pathway.

30
Q

Give an example of a bisphosphonate.

A

Alendronate.

31
Q

How does alendronate work?

A

-onate = bisphosphonate

Inhibit farnesyl phosphatase
– > osteoclast apoptosis

32
Q

For those who are intolerant to bisphophonates, what is the altenative?

A

Strontium Ranelate

33
Q

How does Denosumab work?

A
  • Osteoblasts produce RANK to activate osteoclasts and thus
    bone resorption
  • Denosumab is a monoclonal antibody that inhibits RANK
    signal
  • Reduces fracture risk
34
Q

Give 3 advantages of HRT.

A
  1. Reduces fracture risk.
  2. Stops bone loss.
  3. Prevents menopausal symptoms.
35
Q

Give 3 disadvantages of HRT.

A
  1. Increased risk of breast cancer.
  2. Increased risk of stroke and CV disease.
  3. Increased risk of thrombo-embolism.
36
Q

How does Raloxifene work? What are its side effects?

A

Selective oestrogen receptor modulator (SERM);
= activates oestrogen receptor on bone whilst having no stimulatory effect on endometrium (similar to HRT)

  • Side effects:
    1. Increased risk of thrombus formation
    2. Cramps
    3. Stroke
37
Q

What cells do anabolic treatments target in people with osteoporosis?

A

They increase osteoblast activity.

38
Q

Give an example of an anabolic treatment used in the management of osteoporosis.

A

Teriparatide.

Anabolic treatments increase osteoblast activity.

39
Q

What system is used to predict the risk off osteoporotic fracture?
What things does it consider?

A

FRAX
- BMI, age, smoking, drugs, medical history