Osteoporosis

Question 1

Osteoporosis screening for all

Answer 1

Women >65

Men >70

Question 2

Patients taking oral steroids: What do we do to screen?

Answer 2

Assess fracture risk with a DEXA scan in men or women aged >50 taking prednisone >5mg/day for 3 months

Question 3

T score ranges (DEXA scan results)

Answer 3

Normal: -1.0 and above
Osteopenia: Between -1 and -2.5
Osteoporosis: Below -2.5

Question 4

FRAX model parameters

Answer 4

• based on BMD at femoral neck & patient risk factors

- Age, gender, hx of fractures, hx of hip fractures, BMI, oral steroid use, smoker, ETOH use > 3/day

Question 5

Who gets pharmacologic treatment for osteoporosis

Answer 5

• T score > -2.5
• Patients with a 10-year risk for hip fracture of >3%, and a 10-year risk of major osteoporotic fracture of >20%
• History of fracture of hip or spine

Question 6

Prevention of Osteoporosis

Answer 6

• Dietary intake of calcium (1000-1200 mg)
• Adequate intake of vitamin D
• Regular weight bearing exercise
• Smoking cessation
• Prevention of falls

Question 7

“Bone Protecting” Meds

Answer 7

• Calcium/Vitamin D
• Estrogen
• SERMs
• Bisphosphonates
• Anti-RANK Ligand antibodies

Question 8

“Bone Building” Meds

Answer 8

-Parathormone (PTH) or parathyroid hormone-related protein (PTHrP) analogs

Question 9

Anti-resorptive AND anabolic agents

Answer 9

Sclerostin inhibitors

Question 10

Calcium pearls

Answer 10

• Incomplete absorption –> Usually need Vit D for complete absorption
• Constipation is common

Question 11

Calcium citrate

Answer 11

• Can be taken with or without food
• causes less Gi intolerance
• Higher absorption rate, especially in patients with higher gastric pH

Question 12

Estrogen +/- progestin pearls

Answer 12

• Women with an intact uterus should take a progestin in addition to estrogen to decrease risk of endometrial cancer
• No longer first line*** due to increased risk of breast CA, VTE, CVA

Question 13

SERMs (Selective Estrogen Receptor Modulator)

Answer 13

• Raloxifene
• Tamoxifene (not FDA approved for osteoporosis)

MOA: SERM with estrogen-like effects on bone and anti-estrogen effects on uterus/breast

Question 14

Raloxifene

Answer 14

-Used for the prevention AND treatment of osteoporosis

Question 15

SERM ADRs

Answer 15

• Hot flashes and leg cramps may occur
• Increase the risk of VTE
• Short term studies have not shown an increased incidence of endometrial hyperplasia of uterine CA

Question 16

Bazedoxifene

Answer 16

SERM with estrogen like effects on bone and antiestrogen effects on uterus

-MOA: Inhibits stimulating effect of conjugated estrogens

Question 17

Bazedoxifene indications/interactions

Answer 17

• Tx of moderate-severe vasomotor symptoms
• PREVENTION of osteoporosis in postmenopausal women with intact uterus

-Estrogens are CYP3A4 substrates

Question 18

Bisphosphonates

Answer 18

• Alendronate*
• Risedronate
• Zoledronic acid* (IV qyear or q2years)

Question 19

Bisphosphonates MOA

Answer 19

• Inhibits enzyme in mevalonate pathway which disrupts protein prenylation
• Promotes apoptosis, leads to reduced bone resorption

Question 20

Bisphosphonates Pk (best absorbed when? Half life?)

Answer 20

• Absorbed best on empty stomach

- Plasma half life = 1 hour, can persist in bone for lifetime

Question 21

Clinical Indications for Bisphosphonates

Answer 21

• Prevention and tx of osteoporosis

- Hypercalcemia associated with malignancy and Paget’s

Question 22

Pearls of Bisphosphonates

Answer 22

• Increased BMD leads to decreased vertebral and nonvertebral/hip fx with osteoporosis
• Prevents bone loss in early PMP women
• Prevents bone loss associated with steroid therapy

Question 23

How exactly should a patient take bisphosphonates?

Answer 23

• With 8 ounces of plain water after an overnight fast, remain upright and NPO except water for 30-60min
• Decreases risk of esophagitis
• Take on empty stomach

Question 24

When would IV dosing be beneficial?

Answer 24

• Esophageal abnormalities
• Esophageal intolerance
• Pts who cannot remain upright for 30-60 min
• Pts who forget to take them

Question 25

Bisphosphonates monitoring

Answer 25

- Reeval at 1 month to assess tolerance - CTX at 3 and 6 months - DEXA at 1 year, q2year after to check BMD

Question 26

CI with Bisphosphonates

Answer 26

- GFR <35mL/min - Vit D depletion (25-hydroxy vit D <30 before starting) - Osteomalacia - Hypocalcemia - Impaired swallowing/esophageal disorders - Pregnancy or lactation

Question 27

Interactions with Bisphosphonates

Answer 27

- No CYP | - Food and multivalent cations (Fe2+/Ca2+ supplements, antacids) can interfere with absorption

Question 28

Bisphosphonates ADRs

Answer 28

- PO: GI symptoms (chemical esophagitis rare with nondaily regimens) - IV: transient flu-like febrile illness - IV>PO: ocular effects**, call if decreased vision, eye pain, light sensitivity, or redness - Osteonecrosis of the jaw** (IV>>>PO): refer to dental BEFORE starting bisphosphonates - Atypical femur fractures** often report it "doesn't feel right", consider imaging bilaterally

Question 29

Minimizing ADRs of Bisphosphonates

Answer 29

- Use FRAX to decide if they need it - Stop after 3 (IV) or 5 years (PO) in pts at low risk - Wait additional 3-5 years before taking holiday if high risk - Check BMD with DEXA/FRAX +/- turnover markers - Continue if high risk

Question 30

Anti-RANK Ligand Abs, drug and MOA

Answer 30

Denosumab MOA: shuts down development of osteoclasts

Question 31

Clinical indications of Anti-RANK Ligand Abs

Answer 31

- Tx of osteoporosis in postmenopausal women at high risk who have not responded to bisphosphonates - Prevention of skeletal-related events in pts with bone metastases

Question 32

Anti-Rank Ligand Abs - CI and ADRs

Answer 32

- CI: hypocalcemia pts | - ADRs: fatigue MC, hypocalcemia, ONJ/atypical fx reported

Question 33

PTH/PTHrP Analogs - drugs and MOA

Answer 33

- Teriparatide - Abaloparatide - MOA: stim osteoblast function, increase GI Ca2+ absorption, increase renal tubular reabsorption of Ca2+

Question 34

Clinical Indications of PTH/PTHrP Analogs

Answer 34

-Tx of osteoporosis in pts at high risk of fracture (for up to 2 years)

Question 35

What should you start after stopping PTH/PTHrP analogs?

Answer 35

Antiresorptive drug

Question 36

CI with PTH/PTHrP analogs

Answer 36

- Associated with osteosarcoma*** | - Don't use in pts with hx of skeletal metastases, hyperPTH, pre-existing hypercalcemia

Question 37

ADRs of PTH/PTHrP analogs

Answer 37

- Nausea - HA, dizziness - Arthralgias/myalgias - Hypercalcemia/hypercalciuria (limit Ca2+ intake <1000mg)

Question 38

Sclerostin Inhibitors - drug and MOA

Answer 38

- Romosozumab | - MOA: increase osteoblast activity and bone formation and decreased bone resorption

Question 39

Clinical Indications of Sclerostin Inhibitors

Answer 39

-Tx of osteoporosis in postmenopausal women who are at high risk, failed or cannot tolerate other drugs

Question 40

CI with Sclerostin Inhibitors

Answer 40

CV risk

Question 41

ADRs with Sclerostin Inhibitors

Answer 41

- Arthralgias and HA most common | - Atypical fx/ONJ