Pharmacotherapy Osteoporosis Dr. Dowling

Question 1

What are the major risk factors for Osteoporosis?

Answer 1

-Advanced age
-Current smoker
-History of fracture (after age 50)
-Excessive alcohol intake

Question 2

What is the recommended daily Calcium intake for males and females?

Answer 2

male:
19-70y: 1000 mg daily
>71y: 1200 mg daily

female:
19-50y: 1000 mg daily
51-70y: 1200 mg daily

Question 3

What is the recommended daily Vitamin D intake for males and females?

Answer 3

male:
<70y: 600 mg
>70y: 800 mg

female:
<70y: 600 mg
>70y: 800 mg

800-1000 mg for adults with osteoporosis

Question 4

What is the maximum dose of Ca2+ supplement intake?

Answer 4

500 mg
better absorption with a lower dose
-dietary intake should be prioritized first

ADE: GI, constipation, potential for kidney stones (rare)

Question 5

Dietary Calcium Intake Calculation

Answer 5

add a zero to the % value
ex: 30% = 300 mg
25% = 250 mg

Question 6

How much % elemental calcium do the Ca2+ formulations contain?

Answer 6

Calcium Carbonate: 40% -> preferred
but requires an acidic environment

Calcium citrate: 21%

Question 7

In which patient population is the Calcium Citrate formulation preferred?

Answer 7

-elderly
-patients with acid suppression
-those not taking it with meal

Question 8

How to convert % Vitamin D to units?

Answer 8

multiply by 4

25% Vitamin D -> 100 U

Question 9

What is the treatment serum goal of Vitamin D?

Answer 9

> 30 ng/dl
Vitamin D3 may have a better absorption (recommend D3 if possible)

Question 10

What is the starting dose of Vitamin D supplementation?

Answer 10

5000U for 8-12 weeks (bc it takes about 3 months to reach steady state and reach the target)

->then change to a maintenance dose of 1000-2000 units daily

Question 11

What is the gold standard for the diagnosis and severity of osteoporosis (BMD testing)?

Answer 11

Central DXA scan
T-score displays the severity

Question 12

Which body parts are preferred to be checked with the DXA scan?

Answer 12

Hip
femoral neck
lumbar spine
distal 1/3 of radius

Question 13

Which other device is used to screen the bone density?

Answer 13

Peripheral bone density device (Quantitative Ultrasonography)

Question 14

What is the recommended age for BMD testing in women?

Answer 14

DMX testing for women 65 and older
OR
younger post-menopausal with
hx of fractures without trauma
3 or more months of glucocorticoids

(Evaluate individual risk factors in men ≥ 50 years)

Question 15

How are the DMX scan results evaluated?

Answer 15

T-score: compare BMD to an average BMD of a healthy, sex-matched, 20-29yo white reference population

Z-score: compare BMD to an average BMD of a healthy, age-matched, sex-matched, ethnicity-matched population

Question 16

Which score is used clinically to diagnose osteoporosis?

Answer 16

T-score

Question 17

When is the Z-score used?

Answer 17

in patients with secondary osteoporosis
-> comorbidity, medicine-used osteoporosis, younger than 65, children)

Question 18

When is a patient considered to have Osteopenia?

Answer 18

T-score between -1 to -2.5

below -2.5 –> Osteoporosis
+1 to -1 –> Normal

Question 19

What are examples of medication-induced osteoporosis?

Answer 19

-Long-term glucocorticoids
-Antiepileptics (carbamazepine, phenytoin)
-some chemotherapy drugs

Question 20

What is the dose and duration of glucocorticoids that is considered to increase the risk of osteoporosis?

Answer 20

> 5mg prednisone equivalent daily

3 months or more

Question 21

What is considered high risk based on the FRAX score?

Answer 21

10-year major fracture risk > 20%

10-year hip fracture risk > 3%

Question 22

What are the limitations of the FRAX score?

Answer 22

only estimates the risk for about half of fragility fractures

underestimates risk in the most severe cases

Question 23

Who is eligible for pharmacotherapy to treat osteoporosis?

Answer 23

postmenopausal women and men 50 & over who:

-have a low-trauma fracture
-T-score of -2.5 or lower -> diagnosis of osteoporosis
-T-score of -1 to -2.5 (osteopenia) and a high fracture risk through assessment such as FRAX

Question 24

What is the first-line treatment for Osteoporosis?

Answer 24

Bisphosphonates

Alendronate (PO)
Ibandronate (PO, IV)
Risedronate (PO)
Zoledronic acid (IV)

Question 25

Indication for Bisphosphonate

Answer 25

Treatment: Osteoporosis Postmenopausal women men (except Ibandronate) Prevention of Osteoporosis postmenopausal women

Question 26

How should bisphosphonates be taken?

Answer 26

-take in the morning on an empty stomach -take with 6-8oz of water -sit upright for 30 minutes (ibandroante: 60 min) -> due to GI and esophageal side effects -> due to poor oral bioavailability <1%

Question 27

What are the side effects of Bisphosphonates?

Answer 27

GI upset and irritation Atypical femoral fracture (AFF, rare) - a fraction on a spot of the femur that is unusual in osteoporosis Osetonecrosis of the jaw (ONJ, rare)

Question 28

Contraindications for Bisphosphonate

Answer 28

-Esophageal abnormalities -Hypocalcemia -CrCl < 35

Question 29

How long is the duration of therapy with Bisphosphonates?

Answer 29

consider discontinuing after 5 years if: -BMD is stable -no fractures -short-term fracture risk is low (no environment with activities that increase risk for a fracture)

Question 30

What should be monitored in patients taking Bisphosphonate?

Answer 30

BMD every 1 to 3 years calcium and vitamin D adherence AFF and ONJ

Question 31

What should be taken care of before starting Denosumab?

Answer 31

correct for hypocalcemia (also for Romosozumab) -> administered SubQ every 6 months by a health care provider

Question 32

Risk mitigating intervention for Denosumab

Answer 32

REMS program: make provider and patient aware of ADE: -hypocalcemia -AFF -ONJ -serious infection -dermatologic reactions

Question 33

What should be monitored in patients taking Denosumab?

Answer 33

BMD every 1 to 3 years, serum calcium and vitamin D, signs of AFF or ONJ, pregnancy status

Question 34

Contrainidcations for Denosumab

Answer 34

Hypocalcemia Pregnancy!!

Question 35

Duration of therapy for Denosumab

Answer 35

not established if risk is still high after 5-10 years -> consider extending therapy or switch to Bisphosphonate

Question 36

What is the indication for Raloxifen? (SERM)

Answer 36

Treatment and prevention in postmenopausal women

Question 37

What is the indication for Bazedoxifene + CEE (Duavee®)? (SERM)

Answer 37

Prevention in postmenopausal women

Question 38

When to avoid Raloxifen?

Answer 38

Raloxifen should not be combined with additional systemic estrogens

Question 39

When to avoid Duavee?

Answer 39

avoid in women >60 years old or >10 years postmenopausal

Question 40

What is the BBW for SERMs

Answer 40

Increased risk of VTE, stroke

Question 41

What is the indication for Estrogen replacement drugs?

Answer 41

Prevention of osteoporsis in postmenopausal women

Question 42

When are Estrogen replacements considered?

Answer 42

When women are menopausal and have menopausal symptoms: vasomotor symptoms, systemic symptoms: hot flashes, night sweats ex: Climara, Estrace, Prempro, Vivelle

Question 43

What is the indication of Calcitonin?

Answer 43

Treatment of Osteoporosis in postmenopausal women -may help short-term in vertebral fracture pain -daily nasal spray ADE: rhinitis, runny nose, Antibody development (may decrease the effect)

Question 44

When to consider Calcitonin?

Answer 44

5 years postmenopausal women

Question 45

Indication for PTH analogs -paratides

Answer 45

Teraparatide: Treatment in postmenopausal women and men Abaloparatide: only men they are ANABOLIC - so involved in building bone mass (not just preventing bone loss)

Question 46

How are PTH analogs administered?

Answer 46

-daily SubQ by the patient for up to 24 months (max 2 years lifetime exposure)

Question 47

ADE for PTH analogs

Answer 47

-orthostatic hypotension (sit or lie down when administering the drug) -injection site reaction -dizziness -GI -joint pain, leg cramps, headache -Hypercalcemia, hyperuricemia (kidney stones, gout)!!!

Question 48

Monitor PTH analogs

Answer 48

-BMD every 1-2 years -serum calcium -urinary calcium if prone to kidney stones or hypercalciuria

Question 49

Which drug is an Antiresorptive and Anabolic?

Answer 49

Romosozumab -monthly SubQ by provider -limit: 12 months correct hypocalcemia before start!!!

Question 50

What is the BBW for Romosozumab?

Answer 50

increased risk of MI, stroke, and CV death

Question 51

Max duration for Romosozumab?

Answer 51

1 year then change to antiresorptive

Question 52

Contraindications for Romosozumab

Answer 52

Hypocalcemia recent MI or stroke within 1 year

Question 53

Monitor Romosozumab

Answer 53

BMD at baseline and after 6-12 months serum calcium signs for AFF and ONJ

Question 54

What are the first-line options of therapy?

Answer 54

Bisphosphonate -> if not possible (can't swallow and IV is not possible) -> use Denosumab

Question 55

When is anabolic use considered?

Answer 55

severe case, and very high risk for fracture -start with anabolic for short-term use and consider switching to antiresorptive

Question 56

What are the very high risk factors for fracture

Answer 56

T-score: <-3.0 FRAX Major fracture >30% FRAX Hip fracture >4.5% Fracture… Within past 12 months While on osteoporosis therapy While on meds causing skeletal harm (e.g., long-term glucocorticoids) Hx of multiple osteo fractures High risk/history of injurious falls

Question 57

When might a combo therapy be considered?

Answer 57

2 antiresorptives in a patient with bone loss and already using: hormone therapy for menopause or Raloxifene for cancer -using 2 drugs with different mechanisms is not recommended due to side effects

Question 58

Drugs appropriate for men

Answer 58

Bisphosphonate (antiresorptive) Denosumab (antiresorptive) Teriparatide - PTH analog (anabolic)

Question 59

Which drug cause hypercalcemia, hyperuricemia (uric acid in urine)?

Answer 59

PTH analogs