calcium and bone

Question 1

clinical features of osteoporosis

Answer 1

loss of bony trabeculae -> reduced bone mass -> predispostion to fracture after minimal trauma (no pain but vulnerable to fracture)

Question 2

what happens to bone mass with age

Answer 2

reduces

Question 3

define osteoporosis

Answer 3

bone mineral density greater than or equal to 2.5 standard deviations below average value for young healthy adults (T-score -2.5 or lower); osteopenia if between -1.0 and -2.5

Question 4

what does bone mineral density predict

Answer 4

future fracture risk

Question 5

what measures bone mineral density and 2 locations

Answer 5

DEXA (dual energy x-ray absorptiometry) of femoral neck and lumbar spine

Question 6

how does DEXA measure bone mineral density

Answer 6

mineral (Ca2+) content of bone measured (more mineral, greater bone density); gives T-score

Question 7

osteomalacia vs osteoporosis

Answer 7

osteomalacia: vitamin D deficiency in adults causing inadequately mineralised bone, with an abnormal serum biochemistry (low 25(OH) vit D, low/nomral Ca2+, high PTH due to secondary hyperparathyroidism); osteoporosis: bone reabsorption (osteoclast) exceeds formation (osteoblast), decreased bone mass, normal serum biochemistry so diagnosis via DEXA

Question 8

5 pre-disposing conditions for osteoporosis

Answer 8

postmenopausal oestrogen deficiency, age-related deficiency in homeostasis (men and women), hypogonadism in young women and men, endocrine conditions, iatrogenic

Question 9

how does postmenopausal oestrogen deficiency predispose for osteoporosis

Answer 9

oestrogen deficiency leads to loss of bone matrix, causing subsequent increased risk of fracture

Question 10

example of age-related deficiency in homeostasis (men and women) causing predisposition to osteoporosis

Answer 10

osteoblast senescence

Question 11

3 examples of endocrine conditions which cause predisposition to osteoporosis

Answer 11

Cushing’s syndrome, hyperthyroidism, primary hyperparathyroidism

Question 12

2 examples of iatrogenic conditions causing predisposition to osteoporosis

Answer 12

prolonged use of glucocorticoids, heparin

Question 13

4 treatments for osteoporosis

Answer 13

oestrogen/selective oestrogen receptor modulators for postmenopausal women, bisphosphonates, denosumab, teriparatide

Question 14

what is used to treat postmenopausal oestrogen deficiency as predisposing condition for osteoporosis, and how does it work

Answer 14

oestrogen hormone replacement therapy as has anti-resorptive effects on skeleton, preventing bone loss

Question 15

why do postmenopausal women with an intact uterus need additional progestogen in hormone replacement therapy, as well as oestrogen, to prevent/limit osteoporosis

Answer 15

prevent endometrial hyperplasia and cancer

Question 16

2 reasons why uses of oestrogen hormone replacement therapy is short term option when treating postmenopausal women

Answer 16

increased risk of breast cancer, venous thromboembolism

Question 17

what do bisphosphonates do

Answer 17

bind avidly to hydroxyapatite and are ingested by osteoclasts, impairing ability of osteoclasts to reabsorb bone and impairing bone turnover

Question 18

2 ways bisphosphonates impair ability of osteoclasts to reabsorb bone

Answer 18

decrease osteoclast progenitor development and recruitment, promote osteoclast apoptosis

Question 19

4 uses of bisphosphonates

Answer 19

osteoporosis (first line treatment), malignancy with associated hypercalcaemia (also reduces bone pain and return [Ca2+] to normal), Paget’s disease (reduce bony pain), severe hypercalcaemic emergency

Question 20

administration of bisphosphonates in severe hypercalcaemic emergency

Answer 20

i.v. initially, but rehydration first

Question 21

pharmacokinetics of bisphosphonates: administration and absorption

Answer 21

orally active but poorly absorbed, so take on empty stomach when sitting up (food, especially milk, reduces drug absorption generally)

Question 22

pharmacokinetics of bisphosphonates: where do they accumulate and how long do they last for (including negativity for young people)

Answer 22

accumulates at site of bone mineralisation and remains part of bone until reabsorbed (months, years), which may not be useful in younger patient

Question 23

3 unwanted actions of bisphosphonates

Answer 23

oesophagitis, osteonecrosis of jaw (made adynamic, so have dentla work before starting bisphosphonates), atypical fractures

Question 24

what may be required to prevent oesophagitis when using bisphosphonates

Answer 24

switch from oral to i.v. preparation

Question 25

when is osteonecrosis of jaw a greater risk when using bisphosphonates

Answer 25

when receiving it i.v.

Question 26

what may atypical fractures reflect in use of bisphosphonates

Answer 26

over-suppression of bone remodelling in prolonged use

Question 27

what is denosumab molecularly

Answer 27

human monoclonal antibody

Question 28

what does denosumab do

Answer 28

binds RANKL, inhibiting osteoclast formation and activity, thus inhibiting osteoclast-mediated bone resorption

Question 29

how and when is denosumab administered to treat osteoporosis

Answer 29

subcutaneous injection 6 months/yearly, but is secondary to bisphosphonates

Question 30

what is teriparatide

Answer 30

recombinant PTH fragment (amino-terminal 34 amino acids of native PTH)

Question 31

what does teriparatide do

Answer 31

increases bone formation and bone resorption, but formation outweighs resorption due to dose

Question 32

how and when is teriparatide administered to treat osteoporosis, and why

Answer 32

daily subcutaneous injection, but 3rd line treatment as very expensive