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Clinical Pharmacology > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

Osteoporosis screening for all

A

Women >65

Men >70

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2
Q

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

A

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

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3
Q

T score ranges (DEXA scan results)

A

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

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4
Q

FRAX model parameters

A
  • 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

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5
Q

Who gets pharmacologic treatment for osteoporosis

A
  • 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
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6
Q

Prevention of Osteoporosis

A
  • Dietary intake of calcium (1000-1200 mg)
  • Adequate intake of vitamin D
  • Regular weight bearing exercise
  • Smoking cessation
  • Prevention of falls
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7
Q

“Bone Protecting” Meds

A
  • Calcium/Vitamin D
  • Estrogen
  • SERMs
  • Bisphosphonates
  • Anti-RANK Ligand antibodies
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8
Q

“Bone Building” Meds

A

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

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9
Q

Anti-resorptive AND anabolic agents

A

Sclerostin inhibitors

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10
Q

Calcium pearls

A
  • Incomplete absorption –> Usually need Vit D for complete absorption
  • Constipation is common
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11
Q

Calcium citrate

A
  • Can be taken with or without food
  • causes less Gi intolerance
  • Higher absorption rate, especially in patients with higher gastric pH
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12
Q

Estrogen +/- progestin pearls

A
  • 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
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13
Q

SERMs (Selective Estrogen Receptor Modulator)

A
  • Raloxifene
  • Tamoxifene (not FDA approved for osteoporosis)

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

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14
Q

Raloxifene

A

-Used for the prevention AND treatment of osteoporosis

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15
Q

SERM ADRs

A
  • 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
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16
Q

Bazedoxifene

A

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

-MOA: Inhibits stimulating effect of conjugated estrogens

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17
Q

Bazedoxifene indications/interactions

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

-Estrogens are CYP3A4 substrates

18
Q

Bisphosphonates

A
  • Alendronate*
  • Risedronate
  • Zoledronic acid* (IV qyear or q2years)
19
Q

Bisphosphonates MOA

A
  • Inhibits enzyme in mevalonate pathway which disrupts protein prenylation
  • Promotes apoptosis, leads to reduced bone resorption
20
Q

Bisphosphonates Pk (best absorbed when? Half life?)

A
  • Absorbed best on empty stomach

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

21
Q

Clinical Indications for Bisphosphonates

A
  • Prevention and tx of osteoporosis

- Hypercalcemia associated with malignancy and Paget’s

22
Q

Pearls of Bisphosphonates

A
  • 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
23
Q

How exactly should a patient take bisphosphonates?

A
  • 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
24
Q

When would IV dosing be beneficial?

A
  • Esophageal abnormalities
  • Esophageal intolerance
  • Pts who cannot remain upright for 30-60 min
  • Pts who forget to take them
25
Q

Bisphosphonates monitoring

A
  • Reeval at 1 month to assess tolerance
  • CTX at 3 and 6 months
  • DEXA at 1 year, q2year after to check BMD
26
Q

CI with Bisphosphonates

A
  • GFR <35mL/min
  • Vit D depletion (25-hydroxy vit D <30 before starting)
  • Osteomalacia
  • Hypocalcemia
  • Impaired swallowing/esophageal disorders
  • Pregnancy or lactation
27
Q

Interactions with Bisphosphonates

A
  • No CYP

- Food and multivalent cations (Fe2+/Ca2+ supplements, antacids) can interfere with absorption

28
Q

Bisphosphonates ADRs

A
  • 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
29
Q

Minimizing ADRs of Bisphosphonates

A
  • 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
30
Q

Anti-RANK Ligand Abs, drug and MOA

A

Denosumab

MOA: shuts down development of osteoclasts

31
Q

Clinical indications of Anti-RANK Ligand Abs

A
  • 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
32
Q

Anti-Rank Ligand Abs - CI and ADRs

A
  • CI: hypocalcemia pts

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

33
Q

PTH/PTHrP Analogs - drugs and MOA

A
  • Teriparatide
  • Abaloparatide
  • MOA: stim osteoblast function, increase GI Ca2+ absorption, increase renal tubular reabsorption of Ca2+
34
Q

Clinical Indications of PTH/PTHrP Analogs

A

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

35
Q

What should you start after stopping PTH/PTHrP analogs?

A

Antiresorptive drug

36
Q

CI with PTH/PTHrP analogs

A
  • Associated with osteosarcoma***

- Don’t use in pts with hx of skeletal metastases, hyperPTH, pre-existing hypercalcemia

37
Q

ADRs of PTH/PTHrP analogs

A
  • Nausea
  • HA, dizziness
  • Arthralgias/myalgias
  • Hypercalcemia/hypercalciuria (limit Ca2+ intake <1000mg)
38
Q

Sclerostin Inhibitors - drug and MOA

A
  • Romosozumab

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

39
Q

Clinical Indications of Sclerostin Inhibitors

A

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

40
Q

CI with Sclerostin Inhibitors

A

CV risk

41
Q

ADRs with Sclerostin Inhibitors

A
  • Arthralgias and HA most common

- Atypical fx/ONJ

Clinical Pharmacology (54 decks)

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