Week 11 - Bisphosphonates

Question 1

Bisphosphonates: indications

Answer 1

• Osteoporosis
• High fracture risk
• Hypercalcemia
• Matastatic bone disease
• Paget disease

Question 2

Bisphosphonates: MOA

Answer 2

Inhibit bone resorption by reducing osteoclast number and function (prevents bone breakdown)

Increases bone density

Question 3

Bisphosphonates: pharmacokinetics

Answer 3

• Poorly absorbed orally
• Long half-life (will need to take ‘drug holidays’)
• Renally excreted: not recommended in moderate to severe kidney disease

Question 4

Bisphosphonates: ADR

Answer 4

• Gastric irritation
• Atypical femur fractures
• Severe bone/joint/muscle pain
• Upper GI mucosa irritation (esophagitis, ulcers, dysphagia)
• Hypocalcemia
• Jaw osteonecrosis

Question 5

Bisphosphonates: patient education

Answer 5

• Best given on empty stomach w/ 8 oz water to enhance absorption and stay upright for at least 30 minutes
• D/c before dental work

Question 6

Bisphosphonates: contraindications

Answer 6

• ABSOLUTE contraindications
  
  • Uncorrected hypocalcemia
  • Delayed esophageal emptying (stricture, achalasia)
  • Inability to stand or sit upright for at least 30 minutes
  • Increased risk of aspiration
• Creatinine clearance <35 (renal impairment)
• UGI pathology (e.g. Barretts esophagus)

Question 7

Bisphosphonates: examples

Answer 7

• Risedronate (Actonel)
• Alendronate (Fosamax)
• Ibandronate (Boniva)
• Zoledronic acid (Reclast)

Question 8

Risedronate (Actonel): MOA

Answer 8

Inhibits bone resorption w/o inhibiting bone formation

Question 9

Alendronate (Fosamax): MOA

Answer 9

Highly selective inhibitor of bone resorption

Question 10

Ibandronate (Boniva): MOA

Answer 10

Lack of evidence for prevention of hip or non-vertebral fracture

Question 11

Zoledronic acid (Reclast): ADR

Answer 11

More risk of renal toxicity

Question 12

Zolecronic acid (Reclast): patient education

Answer 12

• Given IV
• Check creatinine before each dose
• Push fluids before and after each dose
• Acetaminophen after infusion may reduce acute phase reaction (influenza like)

Question 13

Bisphosphonates: duration of therapy

Answer 13

• If fracture risk remains high after initial 5 years, consider changing to alternative therapy or extending oral bisphosphonate for up to 10 years
• Consider drug holiday after initial 5 years of therapy if bone mineral density is stable
  
  • Optimal length of drug holiday is usually for up to 5 years

Question 14

Osteoporosis is diagnosed when bone density is ___

Answer 14

2.5 standard deviations below average

Question 15

Osteoporosis risk factors

Answer 15

• >70 years
• Slight build
• Fair complexion
• Low calcium and/or vitamin D diet
• Minimal sun exposure
• Weight <70 kg

Question 16

Osteoporosis: ethnic differences

Answer 16

Young African American women have higher bone density, but risk increases with age

Asian women at high risk

Hispanic women have similar risk as white women

Question 17

What effect does estrogen have on bones?

Answer 17

Estrogen prevents the bone resorption action of PTH

Question 18

True/False: Selective estrogen receptor modulators (SERM) have an estrogenic effect on bones

Answer 18

True - example Raloxifene (Evista)

Question 19

True/False: Starting bisphosphonates in osteopenia status is recommended for most patients

Answer 19

False - no longer considered good practice

Question 20

True/False: There is no evidence of optimal time of duration w/ bisphosphonate therapy

Answer 20

True - some molecules have a 10 year half-life

Question 21

Can estrogen be used to prevent osteoporosis?

Answer 21

Yes - low dose therapy maintains bone mineral density

Question 22

True/False: Taking vitamin D w/ calcium supplementation will decrease absorption

Answer 22

Vitamin D is required w/ calcium supplementation to enhance absorption

Question 23

What patient populations would need bisphosphonates as first line therapy for osteoporosis?

Answer 23

No longer used for preventative therapy

First line for postmenopausal women and men older than 70 years

Question 24

What is considered second line therapy for osteoporosis?

Answer 24

Selective estrogen receptor modulators (SERM)

• Example: Raloxifene (Evista)

Question 25

Osteoporosis: monitoring

Answer 25

Before treatment, r/o other disorders that may cause low bone density

• Hyperparathyroidism, vitamin D deficiency, hyperthyroidism, renal disease

Measure bone mineral density - 10% less = 2x fracture risk

Question 26

How soon after menopause will osteopenia begin?

Answer 26

2-5 years after menopause if no HRT or estrogen therapy is initiated

Question 27

Osteoporosis patient education

Answer 27

• Encourage diet modifications, caffeine, alcohol, and smoking cessation
• Identify role of other medications that contribute (e.g. thyroid hormones)
• Encourage calcium and vitamin D supplementation
  
  • Correct preexisting vitamin D deficiency or hypocalcemia prior to initiating therapy

Question 28

How should patients be instructed to take bisphosphonates?

Answer 28

• Must be upright afterwards (30 minutes)
• Must take ONLY with water
• Monitor for esophageal or gastric distress needed

Question 29

High risk patients who should receive bisphosphonate therapy

Answer 29

• White, Asian ethnicity
• History of eating disorders
• Long term steroid or thyroid medications