IC 14: Drugs for Osteoporosis Flashcards

1
Q

What are some lifestyle and diet modications that can be done for osteoporosis?

A
  • Exercise
  • Calcium supplements
  • Vitamin D supplements
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2
Q

What are some antiresorptive agents that can be used?

A
  • Bisphosphonates
  • RANK ligand inhibitors (e.g. Denosumab)
  • Oestrogen agonists or antagonists
  • Calcitonins
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3
Q

What is the MOA of bisphosphonates for osteoporosis?

A

Slow bone loss by increasing osteoclast (breakdown bone) cell death

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4
Q

What are some drugs that are bisphosphonates?

A
  • Risedronate
  • Alendronate
  • Zoledronic acid
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5
Q

What are some things to note when administering bisphosphonates?

A

Take oral bisphosphonate on empty stomach with at least 240ml of plain water and wait before taking food (at least 30 mins for risedronate and alendronate)

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6
Q

What are the adverse effect associated with taking bisphosphonates?

A
  • Atypical femoral fractures
  • Severe bone, joint or muscle pain
  • Upper GI mucosa irritation
  • Ocular effects
  • Hypocalcaemia
  • Osteonecrosis of the jaw and external auditory canal
  • Nausea
  • Abdominal pain
  • Heartburn-like symptoms
  • IV: flu-like symptoms
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7
Q

What are the contraindications and precautions of bisphosphonates use?

A

Contraindication
* Hypocalcaemia
* Abnormalities of the oesophagus which may delay emptying
* Severe renal impairment (CrCl < 30)
* Pregnancy and lactation

Precautions
* Active upper GI disease
* Risk factors for developing osteonecrosis of the jaw or external auditory canal

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8
Q

What is the MOA of denosumab?

A

Prevent development of osteoclasts

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9
Q

What is the dosage form of denosumab?

A

Subq Injection every 6 months as it is a human monoclonal antibody

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10
Q

What is denosumab administered with?

A
  • 1000mg calcium daily
  • > = 400 IU vitamin D daily
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11
Q

What are the adverse effects of denosumab?

A
  • Muscle, back, bone or joint pain
  • Nausea or vomiting
  • Constipation or diarrhea
  • Slight tiredness
  • Increased cholesterol levels
  • Rarely: osteonecrosis of the jaw, atypical femur fractures
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12
Q

What are the contraindications of denosumab?

A
  • Hypocalcaemia
  • Pregnancy
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13
Q

What is MOA of oestrogen?

A
  • Maintain bone density
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14
Q

In what patients is estrogen typically used in?

A
  • Bone health in younger women
  • Women whose other menopausal symptoms also require treatment
  • Can increase risk of breast cancer and blood clots, which can cause strokes
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15
Q

What is the properties of raloxifene?

A
  • Selective oestrogen receptor modulator
  • Mixed ostrogen receptor agonism and antagonism
  • Reduces rather than increase risk of some types of breast cancer
  • Still increases risk of blood clots and can cause hot flashes
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16
Q

What is the MOA of calcitonin?

A
  • Inhibits osteoclastic bone resorption
  • Reduce blood calcium
17
Q

What is the dosage form of calcitonin?

A
  • Injection (IV, SC or IM)
  • Nasal spray
18
Q

What is the adverse effect of calcitonin?

A
  • Red streaks on skin
  • Injection site reaction
  • Feeling of warmth
  • Redness of face, neck, arms and occasionally upper chest
19
Q

What are the contraindications of calcitonin?

A
  • Hypersensitivity
  • Hypocalcaemia
20
Q

What are some anabolic agents for osteoporosis?

A
  • Sclerostin inhibitors (e.g. Romosozumab)
  • Parathyroid hormone therapies
21
Q

What is the MOA of romosozumab?

A
  • Removes sclerostin inhibition of the canonical Wnt signalling pathway that regulates bone growth
  • Increases bone formation and decreases bone resorption
22
Q

What is the place in therapy for romosozumab?

A
  • For women at high risk of fracture or who have failed or are intolerant to other osteoporosis therapies
23
Q

What is the dosage form of romosozumab?

A

Subq injection once monthly for 12 months

24
Q

What are the adverse effects of romosozumab?

A
  • MI
  • Increased risk of CV death
  • Stroke
  • Transient hypocalcaemia
  • Hypersensitivity reactions
  • Rarely: osteonecrosis of jaw and atypical femur fractures
25
Q

What are the contraindications for romosozumab therapy?

A
  • Hypersensitivity
  • Uncorrected hypocalcaemia
  • History of MI or stroke
26
Q

What is the MOA of parathyroid hormone therapies?

A

Stimulate new bone formation and increase bone strength

27
Q

What is the dosage form of parathyroid hormone therapies?

A

Once daily SC injection

28
Q

What is the maximum duration of parathyroid hormone therapies in a lifetime?

A

24 months due to risk of osteosarcomas

29
Q

What are adverse effects of parathyroid hormone therapy?

A
  • Serious calciphylaxis
  • Worsening of previous stable cutaneous calcification
  • Transient orthostatic hypotension
  • Transient and minimal elevations of serum Ca or hypercalcemia
30
Q

What are the contraindications to parathyroid hormone therapy?

A
  • Hypersensitivity
  • Pre-existing hypercalcemia
  • Skeletal malignancies or bone metastases
  • Other metabolic bone disease like paget’s disease or hyperparathyroidism
  • Unexplained elevations of alkaline phosphatase
  • Previous implant or external beam radiation therapy to the skeleton
  • Hereditary disorders predisposing to osteosarcoma
  • Severe renal impairment
  • Pregnancy
31
Q

How does vitamin D influence calcium balance and osteoporosis?

A
  • With low levels of vitamin D, calcium absorption decreases and low calcium causes increases in PTH secretion. The calcium reservoir of bone is depleted to correct for low calcium absorption in the gut
32
Q

What are factors that encourage the treatment of osteoporosis?

A
  • High fracture risk
  • Past fracture present
  • Bone mineral density lower
  • Age older
  • Risk for falls/bone loss high
33
Q

What is the calculator to check for fracture risk?

A
  • WHO fracture risk assessment tool
34
Q

Why is oral bisphosphonates the first line treatment for osteoporosis (if required)?

A
  • Convenient route of administration
  • Cheap as generics available
  • Adequate efficacy for most patients
  • No significantly more severe adverse effects than other options
35
Q

Which of the drugs for osteoporosis are contraindicated for renal impairment?

A
  • Oral bisphosphonate
  • IV bisphosphonate
  • SC teriparatide
  • SC romosozumab (all <30)
  • Use with caution in SC denosumab (contraindicated if <10)
36
Q

What is administration frequency for the various drugs for osteoporosis?

Hint: there is oral and iv bisphosphonate, SC denosumab, SC teriparatide, SC romosozumab

A
  • Oral bisphosphonate: once a week or once a month
  • IV bisphosphonate: once a year
  • SC denosumab: once every 6 months
  • SC teriparatide: once a day
  • SC romosozumab: once a month
37
Q

Which drug is avoided if patient has reflux oesophagitis?

A

Oral bisphosphonate

38
Q

Should bisphosphonate treatment be continued beyond 5 years?

A
  • Weight risk vs benefits of routine treatment with alendronate or other bisphosphonates beyond 5 years
  • It will have to be individualised to the patient’s risk vs harm of atypical fracture
  • If ten year total risk of fracture still over 20% or if there is a previous vertebra fracture, it will be appropriate to continue treatment
39
Q

Which drug has no hip fracture reduction?

A

SC teriparatide