Loco PBL 2: Osteoporosis

Question 1

What is osteoporosis?

Answer 1

Skeletal disease characterised by low bone density and micro-architectural defects in bone tissue leading to an increased bone fragility and a susceptibility to fractures

Question 2

What is the epidemiology of osteoporosis?

Answer 2

50% of women over 50

Question 3

What are the risk factors for osteoporosis?

Answer 3

Female, old age, BMI <19, malabsorption disorders, family history of hp fracture, long-term use of high dose oral steroids, hyperthyroidism and a reduced androgen level

Question 4

Why does the menopause increase the risk of osteoporosis in women?

Answer 4

Reduced oestrogen production leads decreased inhibition of osteoclasts causing the ratio of degeneration to generation to become skewed leading to bone thinning and weakening

Question 5

Where are the most common sites for osteoporosis-induced fracture?

Answer 5

Hips, vertebra and radius

Question 6

What is the FRAX index used for?

Answer 6

To determine the 10 year probability of acquiring a hip fracture

Question 7

What does a T-score used in a DEXA scan represent?

Answer 7

Compares individual’s bone mineral density against a healthy 30 year old’s

Question 8

What does a Z-score used in a DEXA scan represent?

Answer 8

Compares individual’s bone mineral density against normal for someone of the same age and sex

Question 9

What do the T-scores from a DEXA scan represent?

Answer 9

> -1 SD = normal; -1 to -2.5 SD = osteopenia;

Question 10

What are the treatment options for osteoporosis?

Answer 10

Conservative management, HRT, selective oestrogen receptor modulators, bisphosphonates, raloxifene, denosumab or teraparatide

Question 11

How may osteoporosis be treated conservatively?

Answer 11

With calcium, vitamin D and regular exercise

Question 12

How may HRT be used in the treatment of osteoporosis?

Answer 12

In perimenopausal women for no more than 5 yearsq

Question 13

How may raloxifene be used in the treatment of osteoporosis?

Answer 13

A form of selective oestrogen receptor modulator which prevents osteoporosis in post-menopausal women

Question 14

What is the mechanism of action of raloxifene?

Answer 14

A form of selective oestrogen receptor modulator

Question 15

What is the mechanism of action of bisphosphonates?

Answer 15

Directly inhibit osteoclasts by acting on intrinsic enzyme needed for them to breakdown bone

Question 16

What are the potential side-effects of bisphosphonates?

Answer 16

Giant osteoclasts, osteonecrosis of the jaw, and atypical factors (subtrochanteric and femoral shaft fractures)

Question 17

How may alendronate or risedronate be used in the treatment of osteoporosis?

Answer 17

Forms of bisphosphonates that can directly inhibit osteoclast activity

Question 18

What is the mechanism of action of teriparatide?

Answer 18

A PTH analogue that can activate more osteoblasts than osteoclasts in certain doses

Question 19

How may teraparatide be used in the treatment of osteoporosis?

Answer 19

A PTH analogue that can activate more osteoblasts than osteoclasts in certain doses

Question 20

How may denosumab be used in the treatment of osteoporosis?

Answer 20

Binds to RANKL to prevent it from stimulating the activity and differentiation of osteoclasts; to prevent bone breakdown

Question 21

What is the mechanism of action of denosumab?

Answer 21

Binds to RANKL to prevent it from stimulating the activity and differentiation of osteoclasts

Question 22

What kind of tissue is bone?

Answer 22

Dense connective tissue

Question 23

Which is the most common type of bone?

Answer 23

Cortical (80%), trabecular (20%)

Question 24

What is a Haversian canal?

Answer 24

Cylindrical tubes which run down the axis of long bones to provide compressive strength

Question 25

What is a Volkmann’s canal?

Answer 25

A horizontal branch of the blood vessels supplying the bone, branching from the periosteal blood vessels

Question 26

Outline the composition of the bone matrix.

Answer 26

Type I collagen, proteoglycans, calcium hydroxyapatite on the collagen fibres (leading to hardness and rigidity)

Question 27

Where are osteoprogenitor cells located?

Answer 27

Periosteum or endosteum

Question 28

Which cells secrete sclerostin?

Answer 28

Osteocytes

Question 29

What is the function of sclerostin?

Answer 29

Secreted by ‘happy’ osteocytes to inhibit osteoblasts

Question 30

What is the role of PTH on bone metabolism?

Answer 30

Increases calcium uptake and phosphate excretion by the kidney, increases osteoclasts (due to PTH receptor on osteoblasts which then produce RANKL), increases synthesis of 1, 25 dihydroxyvitamin D from the kidney and increases gut absorption of calcium

Question 31

What stimulates PTH release?

Answer 31

Low serum calcium levels

Question 32

What is the role of calcitonin in bone metabolism?

Answer 32

Inhibits the differentiation of osteoclasts, increases calcium excretion and inhibits calcium gut absorption

Question 33

What stimulates calcitonin release?

Answer 33

Normal/high serum calcium levels

Question 34

What is the role of oestrogen in bone metabolism?

Answer 34

Increases calcium gut absorption and inhibits osteoclasts

Question 35

What is the role of glucocorticoids in bone metabolism?

Answer 35

Decreases gut absorption of calcium, inhibits bone deposition and promotes resorption

Question 36

How does PTH affect sclerostin production?

Answer 36

Inhibits sclerostin in mechanical stress which allows osteoblasts to be stimulated (which eventually activate osteoclasts)

Question 37

How does calcitonin affect sclerostin production?

Answer 37

Upregulates sclerostin secretion to inhibit osteoblasts (to prevent them from activating osteoclasts)