Osteoporosis + Drugs B&B

Question 1

what type of bone does osteoporosis most affect, and why does this make sense?

Answer 1

trabecular (spongy) bone > cortical bone

trabecular bone has high surface area with osteoblasts/clasts on surface

high trabecular bone content in spine, head of femur, and distal radius (wrist)

Question 2

describe why estrogen deficiency in menopause contributes to osteoporosis

Answer 2

estrogen normally inhibits osteoclasts

deficiency —> increased osteoclast activity via:
1. increased RANK-L levels
2. decreased osteoprotegerin

Question 3

what is the classic cause of secondary osteoporosis?

Answer 3

glucocorticoids use - increase bone resorption/ decrease bone formation

Question 4

long-term therapy with which 3 anti-convulsive drugs is associated with secondary osteoporosis? explain the mechanism by which this occurs

Answer 4

phenobarbital, phenytoin, carbamazepine

increase activity of P450 enzymes in liver which increase vitamin D breakdown, causing a decrease in calcium —> PTH is increased, causing bone loss

Question 5

explain the effect on thyroid replacement therapy on bone health

Answer 5

recall hyperthyroidism can cause osteoporosis/fractures by speeding up metabolism (thus speeding up breakdown of bone)

if levothyroxine (T4) is given at too high a dose, iatrogenic hyperthyroidism can occur —> secondary osteoporosis

must measure TSH! if low/suppressed, dose is too high !!

Question 6

A patient is being evaluated for the cause of their osteoporosis. On x-ray, punched-out lytic bone lesions are visible. What is the most likely diagnosis?

Answer 6

multiple myeloma - myeloma cells increase osteoclast activity

Question 7

what are the 2 ways in which osteoporosis is diagnosed?

Answer 7

1. fragility fracture - fall from standing height or less that results in fracture of spine/hip/wrist/humerus/rib/pelvis
2. T score of -2.5 or lower - bone density is measured via DXA scan (dual-energy X-ray absorptiometry), used as screening for women 65+

Question 8

what is the first-line therapy for osteoporosis, and how do these work?

Answer 8

bisphosphonates: analogs of pyrophosphate (used to make nucleotides), modified phosphate groups which bind calcium and accumulate in bone - taken up by osteoclasts and inhibit their action

ex: alendronate, pamidronate, ibandronate, zoledronate

Question 9

drugs that end in “-dronate” and first-line for what condition? how do these work?

Answer 9

bisphosphonates: first line for osteoporosis, analogs of pyrophosphate (used to make nucleotides)

modified phosphate groups which bind calcium and accumulate in bone - taken up by osteoclasts and inhibit their action

ex: alendronate, pamidronate, ibandronate, zoledronate

Question 10

what are 2 classic rare, serious complications of bisphosphonate use (IV or oral)?

Answer 10

bisphosphonates (“-dronates”): first-line for osteoporosis

1. atypical femur fracture - occur below lesser trochanter/ in diaphysis of femur (not due to trauma)
2. osteonecrosis of the jaw - avascular necrosis, most often in setting of underlying dental disease

Question 11

what is the clinical use of teriparatide?

Answer 11

teriparatide = recombinant PTH, treats osteoporosis

continuous PTH causes bone resorption, BUT low dose 1x/daily therapeutic bolus (subcutaneous injection) of PTH increases osteoblast bone formation

[contrast with most osteoporosis therapies, which inhibit osteoclasts]

Question 12

what is the mechanism and clinical use of raloxifene?

Answer 12

raloxifene = SERM (selective estrogen receptor modulator)

anti-estrogen effects in breast and uterus - used for prevention of breast cancer

estrogen mimicking effects in bone - treats osteoporosis

favored due to minimal effects on uterus (endometrial hyperplasia/cancer)

Question 13

denosumab

Answer 13

mAb against RANK-L

blocks osteoblast-mediated activation of osteoclasts —> treats osteoporosis