Osteoporosis

Question 1

What proportion of men and women over 50 will have a fracture due to osteoporosis?

Answer 1

50% women, 20% men.

Question 2

What is a T score?

Answer 2

Standard deviations from a gender-matched young adult mean

Question 3

2 properties other than bone mineral density which contribute to bone strength?

Answer 3

Bone quality (Bone turnover, Mineralisation, microarchitecture)
Bone size

Question 4

What is the most commonly used drug for osteoporosis

Answer 4

Bisphosphonates

Question 5

Describe what osteoporosis is

Answer 5

Osteoporosis is a systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequence increase in bone fragility and susceptibilty to fracture

Question 6

Why do more women suffer from osteoporosis fractures than men?

Answer 6

Women lose trabeculae with age but in men, although there is reduced bone formation, the numbers of trabeculae are stable and their life time risk of fracture is less.
Women also experience higher fracture rates after menopause when osteogren levels decrease

Question 7

What percentage of people are unable to carry out at least 1 activity independently after having a hip fracture?

Answer 7

80% - big impact on QOL

Question 8

What percentage of people will die within 1 yr of having a hip fracture?

Answer 8

20%

Question 9

What percentage of people are unable to walk independently within 1 yr of having a hip fracture?

Answer 9

40%

Question 10

Describe pathophysiology of bone fractures. How does propensity to fall influence fractures?

Answer 10

Fracture risk is dependent on bone strength vs pressure put on bone (trauma to bone). If the pressure on the bone exceeds the strength of the bone, the bone will fracture. Most commonly fractures occur in the setting of normal bone with overwhelming force in a setting of trauma. However, with osteoporosis, there is a weakening of the bone itself which means trauma which wouldn’t normally cause a bone to fracture, now does.

Tying in with trauma is the propensity to fall so if someone is older and unsteady, they will be more likely to fall and cause trauma to their bones and may increase the risk of fracture.

Question 11

What are the factors making up bone strength?

Answer 11

Bone mineral density, bone size, bone quality (architecture, turnover and mineralisation(

Question 12

How does bone mass differ overtime with age? At what age do men and women enter the ‘fracture risk zone’?

Answer 12

Bones grow length wise til about puberty and then bones growth width wise til about mid 30s.
Peak bone mass reached about 35 and after this, bone mass begins to decline
We can see when women go into the menopause, there is a great decline in bone mass and similarly, mens bone mass decreases from around 55 years of age.

Fracture risk = women about 55, men about 65.

Question 13

What area is most likely to be fractured in the young and elderly?

Answer 13

Young - colles’

Elderly - hip followed by vertebrae.

Question 14

What does bone turnover mean?

Answer 14

Bone turnover is the process of resorption by osteoclasts followed by replacement by new bone by osteoblasts with little change in shape.
It occurs throughout a person’s life.

Question 15

What happens in post-menopausal osteoporosis?

Answer 15

There is increased bone turnover which exceeds bone formation. This leads to a net loss of bone and disruption of the bone microarchitecture.
This occurs due to loss of restraining effects of oestrogen on bone turnover.

Question 16

What happens to trabecular bone as we age? How does this affect risk of fractures?

Answer 16

• As we age, bone preferentially keeps vertical trabeculae as most of the force on our joints as vertical.
• This means there is a decrease in trabecular thickness.
• A decrease in connections between horizontal trabeculae occurs and this decreases trabecular strength and increases susceptibility to fractures.
• Removing horizontal structures in bones reduces strength by about 16x
• High turnover in the bone also leads to more areas of resorption and therefore, more points of weakness in the trabecular bone which increases the risk of fractures.

Question 17

Risk factors for osteoporosis (shattered)

Answer 17

Steroid use
Hyperthyroidism, hyperparathyroidism, hypercalciuria
Alcohol and tobacco use
Thin (BMI<19) - reduced skeletal loading increases resoprtion
Testosterone decrease - controls bone turnover
Early menopause - low oestrogen
Renal or liver failure
Erosive or inflammatory bone disease (myeloma, connective diseases, IBD, RA) - increase in inflammatory cytokines which increase resorption
Dietary decreased calcium or malabsorption; T1DM

Question 18

Investigations for osteoporosis?

Answer 18

• X-ray
• Bone densitometry (DEXA)
• Bloods → Ca, PO4, ALP normal

Question 19

What does a DEXA scan do and what does it tell us?

Answer 19

• Low radiation dose and measures the important fracture sites such as the spine, hip and distal radius
• DEXA gives us quantitative information on BMD.
• Bone mineral density (g/cm2) is compared with that of a young healthy adult
• The T score is a standard deviation score and is compared with a gender-matches young adult average (at peak bone mass)
• Each decrease of 1SD in BMD = 2.6x fold increase in risk of hip fracture

Question 20

What T score would indicate osteoporosis and osteopenia? What is severe osteoporosis?

Answer 20

Osteoporosis = -2.5 or worse
Osteopenia = -1 -> -2.5
Normal = 0-> -1.
Severe osteoporosis = T score -2.5 and fracture.

Question 21

What does the FRAX tool do?

Answer 21

Assessment tool for estimating the 10yr risk of osteoporotic fracture in untreated patients.

Question 22

Lifestyle measures for osteoporosis?

Answer 22

• Quit smoking and reduce alcohol
• Weight bearing exercise may increase BMD
• Balance exercises
• Calcium and vitamin D supplements and diet.
• Home-based fall prevention programme with visual assessment and home visit.

Question 23

What are the 2 classes of drug types used in treatment of osteoporosis? What do each of them do?

Answer 23

Anti-resorptive - decreases osteoclast activity and bone turnover
Anabolic - increases osteoblast activity and bone formation

Question 24

What is the first line medical treatment for osteoporosis? How do they work? Why are they used first line? Common side effects associated?

Answer 24

Bisphosphonates - alendronic acid
They work by inhibiting an enzyme in the cholesterol synthesis pathway - FPP synthase.
- Cheap
- Effective
- Many years of experience with them
- Oral or IV choices for administration and different doses available
- SE: photosensitivity, GI upset (common), oesophageal ulcers (drink plenty of water and sit upright for 30m after taking)

Question 25

Why is raloxifene used instead of oestrogen for HRT in osteoporosis?

Answer 25

Raloxifene is a selective oestrogen receptor modulator - partial agonist to oestrogen receptors in bone and helps to maintain bone density and reduce risk of fractures.
It is used preferentially to oestrogen as oestrogen therapy increases risk of breast cancer, stroke, CVD, and venous thrombo-embolism.
Raloxifene decreases breast cancer risk.
Raloxifene is not as powerful as bisphosphonates so used as second line.

Question 26

Do we offer calcium + vitamin D routinely to those with osteoporosis?

Answer 26

No, offer if deficient.

Question 27

What is teriparatide? How does it work?

Answer 27

• Parathyroid hormone analogue
• First anabolic treatment which drives osteoblasts to build bone
• Reduced risk of fractures by 50%
• Increases bone density, improves trabecular structure
• More expensive than bisphosponates so bisphos used first

Question 28

What is denosumab, how does it work? What is a risk associated with its use?

Answer 28

Monoclonal antibody to RANKL which controls the activity of osteoclasts. Denosumab stops the signaling to osteoclasts to stop bone resorption.
Injection subcutaneously every 6 months for post-menopausal osteoporosis or every month for bone metastases
Very good fracture risk reduction
Risk of rebound increase in bone turnover when stopped