Osteoporosis Drugs

Question 1

Osteocytes signal what 2 types of cells?

Answer 1

Osteoblasts and osteoclasts

Question 2

What type of cells break down and resorb bone?

Answer 2

Osteoclasts

Question 3

What type of cells form and deposit bone?

Answer 3

Osteoblasts

Question 4

What is the primary regulator of osteoclasts?

Answer 4

Osteoblasts

Question 5

Is bone remodeling resorption or formation dominant?

Answer 5

Resorption dominant (clasts > blasts) (3 weeks to dig pit, 3-4 months for new bone formation)

Question 6

What is the key for osteoporosis treatment and fracture prevention?

Answer 6

Decreasing bone resorption

Question 7

What is the progression of a monocyte in bone remodeling? (4 steps)

Answer 7

Monocyte → preosteoclast → osteoclast → bone resorption

Question 8

What is the progression of stem cells in bone remodeling? (4 steps)

Answer 8

Stem cells → preosteoblasts → osteoblasts → release RANKL and OPG

Question 9

What has a positive feedback mechanism with osteoclast formation?

Answer 9

RANKL

Question 10

What inhibits RANKL?

Answer 10

OPG

Question 11

What 4 things regulate bone remodeling?

Answer 11

PTH, vit D, calcitonin, estrogen

Question 12

When is PTH release stimulated?

Answer 12

Low serum blood calcium (via calcium sensing receptor, CaSR)

Question 13

How does PTH increase circulating calcium?

Answer 13

↑ osteoclast activity and # via RANKL

Question 14

How does vitamin D increase circulating calcium? (2)

Answer 14

↑ intestinal absorption and ↓ renal excretion, stimulates osteoclast activity through RANKL (in combo w/ PTH)

Question 15

How does calcitonin decrease circulating calcium?

Answer 15

Inhibits osteoclasts to ↓ resorption (also ↓ renal reabsorption)

Question 16

What stimulates calcitonin release?

Answer 16

High circulating calcium

Question 17

When does calcitonin contribute to bone maintenance?

Answer 17

Pregnancy and lactation

Question 18

What does estrogen increase? Decrease?

Answer 18

↓ IL-6 (pro-osteoclast) ↑ OPG (inhibitor of RANKL)

Question 19

What condition is described as the following: Bone mass is decreased Structural integrity of trabecular bone is impaired Cortical bone becomes more porous and thinner Makes bones weaker/ more likely to fracture

Answer 19

Osteoporosis

Question 20

How many standard deviations from N is defined as osteoporosis?

Answer 20

2.5

Question 21

How many standard deviations from N is defined as osteopenia?

Answer 21

1

Question 22

What leads to a 14% death rate from osteoporosis?

Answer 22

Hip fractures leading to subsequent consequences (another common complication = spinal compression fractures (often unknown to pt))

Question 23

What is the greatest RF for osteoporosis?

Answer 23

Postmenopausal women

Question 24

Besides postmenopausal women, what are other less prominent RF’s for osteoporosis? (4)

Answer 24

Long-term glucocorticoid use Thyrotoxicosis Alcoholism Malabsorption syndrome

Question 25

What is the DOC for osteoporosis? (drug class)

Answer 25

Bisphosphonates

Question 26

What are other treatment options for osteoporosis besides bisphosphonates (DOC)? (general)

Answer 26

Calcium and vit D (not always enough on their own), HRT- estrogen, SERMs, calcium regulating hormones

Question 27

What is the MOA for calcium and vit D?

Answer 27

Increase circulating calcium

Question 28

What is the use for calcium and vit D?

Answer 28

Use in combo for osteoporosis (cannot prevent/ treat osteoporosis alone/ adequate calcium intake needed for any other treatment to work/ vit D must be adequate for optimal absorption of calcium)

Question 29

What is the preferred route of administration for calcium?

Answer 29

Chewable (not all preparations absorbed equally)

Question 30

Calcitonin drug class?

Answer 30

Hormone drugs (also includes estrogen and raloxifene)

Question 31

What is the MAO for calcitonin? (2)

Answer 31

Decrease bone resorption of calcium, antagonizes PTH hormone

Question 32

What is the use of calcitonin? (2)

Answer 32

Osteoporosis (not 1st line), Paget's disease

Question 33

What are the 2 possible routes of administration for calcitonin?

Answer 33

Nasal spray or injection

Question 34

What are the SEs of calcitonin? (3)

Answer 34

Allergy, rhinitis/ sinusitis (nasal spray), N/V (injection) (salmon calcitonin = more active but cannot use if allergy)

Question 35

What is the MOA of teriparatide and abaloparatide?

Answer 35

PTH receptor type 1- RG agonist

Question 36

What is the use for teriparatide and abaloparatide?

Answer 36

Osteoporosis (more osteoblast activity) and formation of new bone (only anabolic drugs for osteoporosis)

Question 37

What route of adminitration allows Teriparatide to have intermittent effects?

Answer 37

S.C. injection, short t1/2 = peaks in 30 min, gone in 3 hours

Question 38

What are the SEs of both Teriparatide and Abaloparatide?

Answer 38

Hypercalcemia and hypercalciuria

Question 39

Teriparatide and Abaloparatide can both cause hypercalcemia and hypercalciuria. What is an additional SE of just Abaloparatide?

Answer 39

Hyperuricemia

Question 40

Teriparatide and Abaloparatide are contraindicated in what situation?

Answer 40

Osteosarcoma (black label)

Question 41

What is the MOA for rhPTH?

Answer 41

PTH receptor type 1- R0 agonist

Question 42

What is the use for rhPTH?

Answer 42

Hypoparathyroidism (more osteoclast activity)

Question 43

Teriparatide drug class?

Answer 43

PTH drugs

Question 44

Abaloparatide drug class?

Answer 44

PTH drugs

Question 45

rhPTH drug class?

Answer 45

PTH drugs

Question 46

Denosumab drug class?

Answer 46

Rank-ligand inhibitor

Question 47

What is the MOA for Denosumab? (2)

Answer 47

Inhibits bone resorption, Ab against RANKL = inhibits RANKL (necessary for formation of mature osteoclasts)

Question 48

Denosumab is used for the treatment of osteoporosis in what populations?

Answer 48

Men and postmenopausal women with high fracture risk

Question 49

One of the benefits/ uses of Denosumab is the increase of what?

Answer 49

Bone mass and strength in cortical and trabecular bone

Question 50

What is the route of admintration for Denosumab?

Answer 50

SC injection q 6 months

Question 51

What are the contraindications for Denosumab? (3)

Answer 51

Hypocalcemia and pregnancy \> IMC

Question 52

Alendronate drug class?

Answer 52

Bisphosphates

Question 53

Ibandronate drug class?

Answer 53

Bisphosphates

Question 54

Risedronate drug class?

Answer 54

Bisphosphates

Question 55

Zoledronic acid drug class?

Answer 55

Bisphosphates

Question 56

Route of administration for Alendronate?

Answer 56

Oral

Question 57

Route of administration for Ibandronate?

Answer 57

Oral/ IV

Question 58

Route of administration for Risedronate?

Answer 58

Oral

Question 59

Route of administration for Zoledronic acid?

Answer 59

IV

Question 60

What is the primary MOA for bisphosphonates?

Answer 60

Substitutes for PO4 in Ca binding (incorporated into bone)

Question 61

Although not the primary MOA, what drug class involves P-C-P bond analogs of pyrophosphate and inhibition of osteoclast activity and bone resorption?

Answer 61

Bisphosphates

Question 62

What is the DOC for post-menopausal osteoporosis?

Answer 62

Bisphosphates

Question 63

When must oral bisphosphates be taken due to very poor absorption?

Answer 63

Taken on empty stomach and seated upright for 30 min after taking (taken daily)

Question 64

What is the SE for Bisphosphates (all routes of administration)?

Answer 64

Osteonecrosis of the jaw (will limit bone turnover with each dose = dense bones (non-flexible) = brittle bone)

Question 65

What is the SE for **oral** Bisphosphates? (2)

Answer 65

GI sxs/ discomfort, esophageal ulceration

Question 66

What are the SEs for IV Bisphosphates? (2)

Answer 66

Renal toxicity (if given too fast), N/V

Question 67

What are the contraindications for oral Bisphosphates? (2)

Answer 67

Inability to stand/ sit upright or esophageal disease

Question 68

What is the contraindication for IV Bisphosphates?

Answer 68

Renal disease