Osteoporosis/Calcium and Bone disorder Drugs

Question 1

What are the non-pharmacologic treatments for osteoporosis?

Answer 1

Calcium and Vitamin D (Target: 25OH vitamin D > 30)

Question 2

Antiresorptives include all of the following classes of drugs except:
A. Biologic
B. Hormones
C. SERM (Selective Estrogen Receptor Modulator)
D. Bisphosphonates
E. Anabolic

Answer 2

E. Anabolic (teriparatide)

All the others work against catabolism by osteoclasts

Question 3

Raloxifene is a _____

Answer 3

SERM

Question 4

Alendronate is a _____

Answer 4

Bisphosphonate, Oral

Question 5

Risedronate is a _____

Answer 5

Bisphosphonate, Oral

Question 6

Ibandronate is a _____

Answer 6

Bisphosphonate, Oral or IV

Question 7

Zoledronic acid is a _____

Answer 7

Bisphosphonate, IV

Question 8

Denosumab is a _____ agent used in osteoporosis treatment

Answer 8

Biologic

Question 9

What two hormones can be used as antiresorptive/anticatabolic osteoporosis meds?

Answer 9

Calcitonin and Estrogen

Question 10

True or False: Raloxifene is a more potent antiresorptive than denosumab and bisphosphonates

Answer 10

False

Question 11

Raloxifene is an _____ in bone and an ______ in breast tissue

Answer 11

agonist, antagonist

*In bone, inhibits osteoclasts - improve BMD, decrease fracture risk
In breast, reduces risk of breast cancer

Question 12

Side effects of Raloxifene include which two of the following:
A. DVT
B. Headaches
C. Hot flushes
D. Palpitations
E. Thickening of endometrium

Answer 12

A. DVT and C. Hot flushes

*Raloxifene is neutral on cardiovascualar/endometrium

Question 13

Bisphosphonates work in treating osteoporosis by

Answer 13

Impair osteoclast function
Decrease osteoclast differentiation and increase apoptosis
Overall effect - Increase BMD and decrease fracture risk

Question 14

Side effects of bisphosphonates include all of the following except:
A. Flu-like symptoms w/ IV use
B. Hyponatremia
C. Hypocalcemia
D. Bone and muscle pain
E. Esophagitis w/ oral use

Answer 14

B. Nope

*E. avoid oral use in patients with upper GI disease, Barret’s esophagus

Question 15

Bisphosphonates are contraindicated in patients with creatinine clearance ___

Answer 15

Less than 30

Question 16

What are the two potential long-term side effects of bisphosphonates?

Answer 16

Atypical subtrochanteric fractures

Osteonecrosis of the jaw

Question 17

Basis of atypical subtrochanteric fractures and bisphosphonate use

Answer 17

Use of bisphosphonates decreases rate of bone turnover that is necessary for repair of daily wear and tear -> accumulation of microcracks in the bone -> transverse/short oblique fractures with little/no trauma

Question 18

It takes a median of 7 years for subtrochanteric fractures to occur in bisphosphonate use. What can be done to prevent this?

Answer 18

Give the patient “drug holidays” every 4-5 years

Question 19

What is osteonecrosis of the jaw?

Answer 19

Area of exposed necrotic bone +/- infection

• more common with IV bisphosphonates, usually after invasive dental procedures
• avoid invasive dental procedures, be hygienic!

Question 20

Potential mechanism of osteonecrosis

Answer 20

Decreased jaw bone turn over -> accumulation of microcracks
Antiangiogenic effects of bisphosphonates -> necrosis
Invasive dental work -> microbes track into bone

Question 21

Denosumab mechanism of action

Answer 21

Binds to RANKL (released by osteoblast) to prevent it from binding RANK receptor on osteoclasts ->prevent osteoclast differentiation/maturation

Question 22

Denosumab is administered by

Answer 22

Subcutaneous injection every 6 months

Question 23

Side effects of denosumab

Answer 23

Hypocalcemia
Possible increase in infections/neoplastic effects
Concern for subtrochanteric fractures and ONJ

Question 24

True or False: Denosumab does not have any renal restrictions and can be used in patients with creatinine clearance

Answer 24

True

Question 25

True or False: Calcitonin is not a potent antiresorptive, but can provide some relief of acute pain in vertebral fractures

Answer 25

True

Question 26

Estrogen is not recommended as treatment of osteoporosis, why?

Answer 26

Side effects! Breast cancer and cardiovascular disease

Question 27

Teriparatide is human recombinant PTH1-34, who does it differ from antiresorptives?

Answer 27

It's the only current anabolic drug. Induce differentiation/maturation of osteoblasts, increase function, reduce apoptosis.

Question 28

Teriparatide is administered daily by

Answer 28

Subcutaneous injection *money money money, expensive, so only for severe cases or if other treatments fail or patient contraindicated

Question 29

Side effects of Teriparatide

Answer 29

Increase uric acid - gout attacks Hypercalcemia - small, rare Osteosarcoma concern - 2 year lifetime Tx limit

Question 30

Teriparatide is contraindicated in

Answer 30

Patients with high risk of osteosarcoma: kids, Paget, prior radiation Patients with cancer in last 5 years Patients with elevated PTH

Question 31

Cessation of teriparatide results in loss of gains in BMD, what can be done to minimize this?

Answer 31

Follow-up with antiresorptives

Question 32

Signs and Symptoms of hypercalcemia

Answer 32

CNS: fatigue, lethargy, depression Neuromuscular: weakness Cardiovascular: HTN, bradycardia, Short QT Renal: polyuria, fluid depletion, kidney stoens GI: nausea, vomiting, constipation, anorexia

Question 33

Cinacalcet is a

Answer 33

calcimimetic * mimics calcium, binds CaSR on parathyroid cells, decrease PTH secretion -> decrease serum calcium * used in cases of very high calcium in primary hyperparathyroidism

Question 34

Main side effect of cinacalcet

Answer 34

nausea

Question 35

Symptoms and Signs of hypocalcemia

Answer 35

Neuromuscular: parasthesias (fingers/around mouth), tetany, seizures, confusion/fatigue/depression Cardiac: Prolonged QT PE: carpopedal spasm and Chvostek's sign

Question 36

If PTH is low, serum phosphrus will be ____

Answer 36

High. PTH is needed to promote renal P excretion

Question 37

If PTH is low, urine calcium is ____

Answer 37

High. PTH needed to promote renal calcium reabsorption

Question 38

List 4 causes of PTH elevation with low serum calcium

Answer 38

``` Poor calcium intake Vitamin D deficiency PTH resistance (pseudohypoparathyroidism) Vitamin D resistance ```