Osteoporosis

Question 1

What is osteoporosis?

Answer 1

• progressive loss of bone mass associated with change in bone micro-architecture
• associated with reduced cross linking within trabecular cone resulting in cortical thinning

Question 2

How common is osteoporosis?

Answer 2

One third of women over 50 will sustain in osteoporotic fracture in their lifetime

Question 3

What is remodelling?

Answer 3

• a normal process continually taking place within the bone
• allows bone to adapt to stressors and repair microdamage
• the net product of bone formation and reabsorption

Question 4

What are the stages of bone remodelling?

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Answer 4

• activation of osteoclasts from circulating precursor cells, mediated by receptor binding of NF-kB ligand
• aggregation and adherence of osteoclasts to regions of active bone reabsorption on the trabecular plate
• osteoblastic breakdown of bone matrix, releasing calcium, minerals and active growth factors
• simultaneous osteoblastic deposition of osteoid with subsequent mineralization as calcium and phosphate

Question 5

What happens to bone remodelling in postmenopausal women?

Answer 5

• Shifts towards bone reabsorption, leading to net bone loss
• Osteoclasts function in a less regulated manner , perforating through the trabecular plate
• There is no framework for osteoblast activity and structural integrity is lost
• This loss of connectivity between the trabecular plates is typical of the microstructure changes associated with osteoporosis

Question 6

What are the risk factors for primary osteoporosis?

Answer 6

Female gender 
Previous fragility fracture 
Maternal history of hip fracture 
Current smoker 
Alcohol intake >3 units/day 
Glucocorticoids >3 months at more than 5 mg/day 
Low calcium and vitamin D deficiency 
Low BMI (<19 kg/m2)

Question 7

What are the causes of secondary osteoporosis?

Answer 7

Rheumatoid arthritis 
Hyperthyroidism/hyperparathyroidism 
Premature menopause (<45yo) 
Chronic malabsorption or malnutrition (e.g. coeliac) 
Chronic liver disease

Question 8

What risk stratification tool is used?

Answer 8

The FRAX tool was developed by the WHO to calculate 10 year fracture risk

Question 9

What investigations are used in osteoporosis?

Answer 9

Blood tests - FBC, UE, LFT, TFT, Ca, vitamin D, PTH, coeliac serology, myeloma screen

Question 10

What is a DEXA scan?

Answer 10

Gold standard investigation used to establish a formal diagnosis of osteoporosis by measuring bone mineral density

Question 11

How is a DEXA scan reported?

Answer 11

T score - the number of standard deviations (SDs) above or below the bone mineral density for an average 25 year old

Question 12

What T score indicated osteoporosis?

Answer 12

T score of 2.5 SDs below normal represents osteoporosis

Question 13

What is a Z score?

Answer 13

A Z score coressponds to the number of SDs above or below the bone mineral density in age-matched controls

Question 14

When would a whole spine X-ray be useful?

Answer 14

To establish the presence of asymptomatic fracture

1/3 of vertebral fractures fall into this group

Question 15

Which bone turnover markers are used in specialist clinics to establish compliance and effectiveness ?

Answer 15

serum C-terminal telopeptide (CTX) levels

Question 16

What supplement should osteoporosis patients be commenced on?

Answer 16

Vitamin D

Co administration with calcium will depend on baseline serum calcium levels and dietary intake

Question 17

What is the mainstay of treatment for osteoporosis?

Answer 17

Bisphosphonates

Question 18

What is the mechanism of action of bisphosphonates?

Answer 18

They inhibit osteoclastic bone reabsorption, which in turn results in reduced bone formation and turnover as a whole is reduced

Question 19

For how long do patients usually receive bisphosphonates?

Answer 19

3-5 years

Question 20

Why are bisphosphonates stopped after 3-5 years?

Answer 20

Beyond this the benefits of therapy must be balanced against the risk of atypical subtrochanteric fractures and osteonecrosis of the jaw

Question 21

What is alendronate?

Answer 21

Oral bisphosphonate

Question 22

When is zolendronic acid used?

Answer 22

Intolerant to oral bisphosphonate

Question 23

What is zolendronic acid?

Answer 23

An IV bisphosphonate

Question 24

What is denosumab?

Answer 24

monoclonal antibody to RANK-L

reducing its availability at receptor sites at the osteoclast surface

Question 25

When is denosumab used?

Answer 25

renal impairment

intolerant to oral bisphosphonates

Question 26

What is Raloxifene?

Answer 26

selective oestrogen
receptor modulators
oestrogen agonist effects on bone

Question 27

When is Raloxifene used?

Answer 27

Secondary prevention, early post menopausal women with vertebral fracture

Reduces risk of oestrogen positive breast cancer

Question 28

What is teriparatide?

Answer 28

Anabolic
Directly stimulates osteoblastic bone formation
(daily injection over 18-24 months)

Question 29

What are the indications for teriparatide use?

Answer 29

severe osteoporosis = T-score of -4.0 or -3.5 in the context of two or more fragility fractures

Treatment failure

Question 30

What are the cautions of using tereparatide?

Answer 30

hypercalcaemia

Question 31

What are the cautions of using raloxifene?

Answer 31

thromboembolic disease

Question 32

What are the cautions of using denosumab?

Answer 32

ensure vitamin D replete
atypical femoral fractures and osteonecrosis of the jaw
caution if at high risk of injections

Question 33

What are the cautions of using alendronate?

Answer 33

Upper GI side effects
Compliance with treatment directions
Poor bioavailability

Question 34

What are the cautions of using Zolendronic acid?

Answer 34

ensure vitamin D replete