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Bone Health Flashcards

1
Q

Osteoporosis

A

Progressive loss of bone mass and skeletal fragility

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2
Q

What patient population does OA occur most in?

A

Post menopausal women

Can also occur in elderly men and in patients who take medications that induce bone loss, such as glucocorticoids.

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3
Q

Paget disease

A

Disorder of bien remodeling that results in disorganized bone formation and enlarged or misshapen bones.

Usually limited to one or a few bones.

May experience bone pain, bone deformities, or fractures.

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4
Q

Osteomalacia

A

Softening of the bones that is most often attributed to vitamin D deficiency.

Known as Rickets in children.

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5
Q

S/s of osteomalacia

A

Bone pain, fractures, leg weakness

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6
Q

Osteoclasts

A

Break down bone - bone resorption

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7
Q

Osteoblasts

A

Cells that build bone

Calcium phosphate crystals known as hydroxyapatite are deposited in new bone matrix - essential for bone strength

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8
Q

When does bone loss occur?

A

When bone resorption exceeds bone formation

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9
Q

Prevention of osteoporosis

A

Vitamin D
Calcium
Weight-bearing exercises
Smoking cessation
Avoidance of excessive alcohol intake

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10
Q

Calcium citrate vs calcium carbonate

A

Calcium citrate
- 21% elemental calcium
- better tolerated
- taken with or without food
- preferred in pts taking acid-reducing agents

Calcium carbonate
- 40% elemental calcium
- inexpensive and commonly used
- should be taken with meals for best absorption
- poorly absorbed with coadministration of H2 receptor agonists or PPIs

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11
Q

Vitamin D and calcium absorption

A

Vitamin D is essential for absorption of calcium and bien health

Older patients often at risk of vitamin D deficiency

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12
Q

When is pharmacological therapy needed?

A
  • in post menopausal women
  • men over 50 or have previously had an osteoporotic fracture
  • a bone density that is 2.5 SD or more below
  • people with osteopenia with high probability of fx
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13
Q

Bisphosphonates

A
  • alendronate
  • risedronate
  • zoledronic acid
  • etidronate
  • ibandronate
  • pamidronate
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14
Q

Bisphosphonates for postmenopausal osteoporosis

A
  • alendronate
  • risedronate
  • zoledronic acid
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15
Q

MOA of Bisphosphonates

A

Bind to hydroxyapatite crystals and decrease osteoclastic bone resorption - increases bone mass and decreases risk of fx.

Alendronate has beneficial effects for several years; discontinuation causes gradual loss of effects.

Zoledronic acid has high affinity for mineralized bone, decreases bone resorption for up to 1 year after 1 IV infusion.
- First line therapy for Paget’s disease

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16
Q

Pharmacokinetics of Bisphosphonates

A

PO alendronate, risedronate, and ibandronate dosed daily, weekly, or monthly
-Absorption is poor (less than 1% absorbed)
-Food and meds greatly interfere with absorption
-Rapidly cleared from plasma - avidly bind to hydroxyapatite in the bone
- Once bound, cleared over hours to years

Elimination primarily via kidneys - avoid in severe renal impairment

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17
Q

Adverse effects of Bisphosphonates

A
  • Diarrhea
  • Abdominal pain
  • Musculoskeletal pain

Rare:
* Osteonecrosis of the jaw (ONJ)
- Risk factors: higher dose, long duration, IV adm, dental extractions or implants, use of glucocorticoids, diabetes, smoking
* Atypical femur fx
- Risk factors: long term use

Alendronate and risedronate, and ibandronate are associated with esophagitis and esophageal ulcers
- Remain upright after taking

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18
Q

What is recommended to decrease adverse effects of bisphosphonates

A

Consideration of drug holiday after 5 years of PO

3 years for xoledronic acid

Should not be d/c’d in women who remain at high risk of fx

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19
Q

RANKL Inhibitor

A

Denosumab: monoclonal antibody; targets receptor activator of nuclear factor kappa-B ligand (RANKL); binding prevents activation of RANK receptors on osteoclasts - reduces osteoclast formation and bone resorption

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20
Q

Who is Denosumab approved for?

A
  • Postmenopausal women at high risk of fx
  • Alternative first-line tx
  • Osteoporosis in men
  • Glucocorticoid-induced osteoporosis
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21
Q

Administration of Denosumab

A

SubQ every 6 mo

If d/c’d - should start an alternative agent, such as bisphosphanate to prevent rebound increase in bone resorption.

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22
Q

Adverse effects of Denosumab

A
  • GI upset
  • Bone pain
  • Increased risk of infections
  • Dermatologic reactions
  • Hypocalcemia

Rare:
* ONJ
* Atypical fx

23
Q

Parathyroid agents

A

Teriparatide: recombinant form of human parathyroid hormone

Abaloparatide: analog pf parathyroid hormone-related peptide

Act as agonists at the parathyroid hormone receptor. Stimulates osteoblastic activity and increased bone formation and bone strength.

24
Q

Administration of parathyroid agents

A

SubQ daily

Should he used for no more than 2 years than switch to another antiresorptive agent to maintain

25
Q

Who gets parathryoid agents?

A

Reserved for pts with high-risk of fx and those who have failed or unable to tolerate other therapies.

26
Q

Adverse effects of parathyroid agents.

A
  • Injection site reactions
  • Hypercalcemia
  • Orthostatic hypotension

Hyperuricemia may occur with abaloparatide.

Associated with increased risk of osteosarcoma in rats - contraindicated in pts at risk for osteosarcoma

27
Q

Sclerostin Inhibitor

A

Romosozumab: monoclonal antibody and an inhibitor of sclerostin

Sclerostin is an important regulatory factor in bone remodeling - inhibits bone formation

MOA: romosozumab binds to sclerostin and inhibits its action - thereby promotes osteoblast activity and bone formation

Secondary MOA: decrease in bone resorption

28
Q

Who gets Romosozumab?

A

Postmenopausal osteoporosis with high risk of fx

29
Q

Administration of Romosozumab

A

2 SubQ inj 1x/mo for 1 yr

After 1 yr, begin different antiresorptive agent.

30
Q

Adverse effects of Romosozumab

A
  • Arthralgias
  • HA
  • Injection site reactions

Avoid in pts with hx of MI or stroke

31
Q

Selective Estrogen Receptor Modulators

A

Estrogen therapy effective for prevention of postmenopausal bone loss. Lower estrogen after menopause promotes proliferation of osteoclasts (bone mass can rapidly decline)

Raloxifene: has estrogen-like effects on bone and estrogen antagonist effects on breast and endometrial tissue
* Increases bone density without increased risk of endometrial cancer
* Decreases risk of invasive breast cancer
* Used as an alternative tx - has not been shown to reduce nonvertegral or hip fx

Bazedoxifene

32
Q

Why is estrogen therapy not used regularly anymore?

A

Estrogen may increase the risk of endometrial cancer (when used without a progestin in women with uterus), breast cancer, stroke, VTE, and coronary events.

May be used with severe symptoms of menopause and contraindications to other therapies.

33
Q

Adverse effects of Raloxifene

A
  • Hot flashes
  • Leg cramps
  • Increased risk of VTE
  • Should be avoided in pts with hx of DVTs, PEs
34
Q

Calcitonin

A

Peptide that secreted by the thyroid gland, binds to osteoclasts and inhibits their resorptive activity

Drug is salmon calcitonin (greater potency and duration thatn human calcitonin)

35
Q

Who gets Calcitonin?

A

Used more for management of hypercalcemia

Women who are at least 5 years postmenopausal

36
Q

Adverse effects of Calcitonin

A
  • Increased risk of new malignancy with long-term administration
  • Rhinitis
  • Injection site reactions
37
Q

Unique property of Calcitonin

A

Relief of pain associted with osteoporotic fx - may be given short-term with recent, painful fc

38
Q

Administration of Calcitonin

A
  • Intranasal
  • SubQ
  • IM

Only used if other osteoporosis agents are not tolerated

39
Q

A 52-year-old woman has a hx of rheumatoid arthritis, diabetes, HTN, and heartburn. Her medications include methotrexate, prednisone, metformin, hydrochlorothiazide, lisinopril, and calcium carbonate. She is worried about the risk of osteoporosis as she approaches menopause. Which of her medications is most likely to contribute to the risk of developing osteoporosis?
a. Calcium carbonate
b. Hydrochlorothiazide
c. Lisinopril
d. Prednisone

A

d. Prednisone

Glucocorticoids (for example, prednisone at a dose of >/= 5 mg/dayfor greater than 3 months) are a significant risk factor for osteoporosis.

The other medications have not been shown to increase the risk of osteoporosis.

Calcium carbonate and hydrochlorothiazise (diuretic that increases calcium retention) may be benefical for pts at risk of osteoporosis.

40
Q

Which of the folloiwng is correct regarding the pharmacokinetics of bisphosphantes?
a. Bisphosphonates are well absorbed after PO adm
b. Foor or other mediciations greatly impair absorption of bisphosphonates.
c. Bisphosphonates are mainly metabolized via the cytochrome P450 system
d. Elimination half-life of bisphosphantes ranges from 4 to 6 hours

A

b. Foor or other mediciations greatly impair absorption of bisphosphonates.

Food and other medications decrease absorption of bisphosphonates, which are already poorly absorbed (<1%) after PO adm.

Bisphosphonates are cleared from the plasma by binding to bone and being cleared from the kidney (not metabolized by the CYP450 system).

The elimination half-life may be years.

41
Q

A 56-year-old woman who has been diagnosed with postmenopausal osteoporosis has no hx of fx and no other pertinent medical conditions. Which of the following is most appropriate management of her osteoposis?
a. Alendronate
b. Calcitonin
c. Romosozumab
d. Raloxifene

A

a. Alendronate

Bisphosphonates are first-line therapy for osteoporosis in postmenopausal women without contrainidcations.

Raloxifene is an alternative therpay that may be less efficacious (espeiclaly for nonvertebral and hip fx) and should only be used in women unable to take bisphosphonates or denosumab.

Calcitonin is not recommended.

Romosozumab is best used for pts at high risk of fx.

42
Q

A patient has been taking alendronate for postmenopausal osteoporosis for 5 years with a sligth incrase in bone mineral density and no occurrence of fx. Risk of which adverse effect mgith warrant consideration of a drug holiday from alendronate in this patient?
a. Atypical femur fx
b. Hypercalcemia
c. Osteosarcoma
d. Rhinitis

A

a. Atypical femur fx

Atypical femur fx are associated with long-term use of bisphosphonates (greater than 5 years). Therefore a drug holiday might be considered since the pt has had no fx.

Hypercalcemia and osteosarcoma are associated with the parathyroid hormone analogs.

Rhinitis is associated with intranasal calcitonin.

43
Q

Which of the following best describes the medhanicms of action of denosumab in the treatment of osteoporosis?
a. Parathyroid hormone analog
b. RANKL inhibitor
c. Selective estrogen receptor modulator
d. Sclerostin inhibitor

A

b. RANKL inhibitor

Denosumab is a monoclonal antibody that targets receptor avtivator of nuclear factor kappa-B ligand (RANKL) and ihibits osteoclast formation and function.

Teriparatide and abaloparatide are parathyroid agents.

Raloxifene is a SERM.

Romosozumab is a sclerostin inhibitor.

44
Q

Use of which agent for osteoporosis should be limited to no more than 2 years?
a. Calcitonin
b. Denosumab
c. Teriparatide
d. Zoledronic acid

A

c. Teriparatide

Use of the recombinant parathryoid hormone, teriparatide, should be limited to 2 years. Use beyond 2 years has not been studied and is not recommended.

The other agents do not have such limitations.

45
Q

Which of the following characteristics would make a patient the most appropriate candidate for abaloparatide treatment for postmenopausal osteoporosis?
a. Fear of needles
b. Desire for once-monthly therapy
c. History of multiple vertebral fx
d. T-score of -2.0 and no hx of fx

A

c. History of multiple vertebral fx

Abaloparatide, an analog of parathyroid hormone-related peptide, is best used in patietns with a high risk of fx, such as those with a hx of multiple vertebral fx. Abaloparatide is administered via daily SubQ.

Pts with a T-score indicating osteopenia and no hx of fx may or may not require pharmacotherapy depending on the risk of future fx.

46
Q

A 55-yr-old man is dx with Paget disease. He has no other significant medical hx. Which agent would be most appropriate for tx of Paget disease in this pt?
a. Abaloparatide
b. Denosumab
c. Raloxifene
d. Zoledronic acid

A

d. Zoledronic acid

Zoledronic acid is the preferred agent for tx of Paget disease because of its efficacy and once-yearly adm.

The other agents do not have an indication for Paget disease.

47
Q

A 67 yo woman c/o severe back pain and is found to have multiple vertebral fx related to osteoporosis. The pt has a PMH of HTN, CKD, and MI 6 mo ago. Which of the following would exclude the use of romosozumab in this pt?
a. CKD
b. HTN
c. MI
d. Vertebral fx

A

c. MI

Romosozumab should be avoided in pts with a hx of MI (especially recent MI), as a small, but significant increase in MI and stroke occured in clinical studies.

Multiple vertebral fx is a reason to consider (not exclude) therapy with romosozumab.

HTN and renal dysfunction are not contradinications for use of this agent.

48
Q

A 55 yo woman with postmenopausal osteoporosis has a past medical hx of ETOH use disorder, alcoholic liver disease, erosive esophagitis, and hypothyroidism. Which is the primary reason oral bisphosphonates should be used with caution in this pt?
a. Age
b. Errosive esophagitis
c. Liver disease
d. Thyroid disease

A

b. Errosive esophagitis

Bisphosphonates are known to cause esophageal irritation and should be used with caution in a pt with a hx of erosive esophagitis.

Age is not a factor for consideration in bisphosphate use.

Liver disease is not a contrainidcation to bidphosphonate use, since bisphosphonates are mainly cleared via the kidney.

Thyroid disease is not a contraindication to bisphosphonate use, although overaggressive replacement of thyroid may contribute to osteoporosis.

49
Q

Which of the following bone mineral density (BMD) scores (as compared to the mean in young women) indicates a potetnail need for pharmacolgoical intervention?
a. BMD - 2.5 SDs (below) mean and T-score </+ 2.5
b. BMD +2.5 SD (above) normal and a pt who has already expereienced at least 1 fx
c. BMD +/- 1 SD of t and a T-score of >/+ 1
d. BMD -1.25 SD and T-score between -1 and -2.5

A

a. BMD - 2.5 SDs (below) mean and T-score </+ 2.5

The lower your score, the weaker your bones are:
T-score of -1.0 or above = normal bone density
T-score between -1.0 and -2.5 = low bone density, or osteopenia
T-score of -2.5 or lower = osteoporosis

When the bone density is 2.5 SDs below the mean average, treatment is recommended by guidelines from multiple professional and expert organizations.

50
Q

A 70 yo woman suffering from osteoporosis and HTN and a breast cancer survivor, has been treated for the last 3 years with raloxifene and calcium carbonate (1.5 g daily) for osteoporosis and with hydrochlorothiazide for HTN. In spite of the therapy, a recent bone mineral density showed a significant decrease in bone mass. Which of the following would be an appropriate change in the tx plan of this pt?
a. Add calcitonin to the present regimen
b. Increase the daily dose of calcium carbonate
c. Substitute ethinyl-estrogen for the raloxifene
d. Substitute propranolol for the hydrochlorothizide
e. Add alendronate to the present regimen
f. Add prednisone to the present regimen

A

e. Add alendronate to the present regimen

Raloxifene was not a good choice for bone health, but it was a good choice for her estrogen-sensitive breast cancer

51
Q

A 55 yo woman complained to her physician of a persistent back pain of 3 days duration. A dual-energy x-ray absorptiometry showed diffuse osteoporosis of the spine and hips. The physician ordered calcium and vit D supplementation and alendronate, 10 mg daily. Which of the following actions most likley mediated the therapeutic effect of alendronate in this patient?
a. Stimulation of osteoblast activity
b. Stimulation of intestinal calcium absorption
c. Inhibition of renal synthesis of calcitrol
d. Inhibition of osteoclast activity

A

b. Stimulation of intestinal calcium absorption

Recall that vit D influences calcium absorption in the GI tract and that calcium is needed to enhance bisphosphonate actions.

52
Q

A 56 yo woman complained to her physician of frequent heartburn and pan in the substernal region. The woman, recently diagnosed with postmenopausal osteoporosis, started an appropriate therapy two weeks previously. Which of the following drugs most likley caused the pateint’s symptoms?
a. Raloxifene
b. Calcitonin
c. Prednisone
d. Teriparatide
e. Ibandronate

A

e. Ibandronate

Ibandronate: bisphosphonate
Raloxifene: SERM
Teriparatide: Parathryoid agent
Prednisone: glucocorticoid
Calcitonin: peptide secreted by thyroid gland

53
Q

Which of the following ADRs is most concerning when the patient is prescribed a bisphosphonate?
a. Drug-drug ineractions through CYP2C19 metabolizing enzymes
b. N/V
c. Overtreatment with joint dysfunction
d. Necrosis of the jaw

A

d. Necrosis of the jaw

ONJ is rare ADR
Increased risk with:
* Higher dose and longer duration of therapy
* IV adm
* Dental extractions or implants
* Use of glucocorticoids
* Diabetes
* Smoking

Advanced Pharm (17 decks)

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