Osteoporosis

Question 1

What are the impt counselling points for Oral Bisphosphonates?

Answer 1

1) Take on an empty stomach w/ at least 240ml of plain water.
2) Wait at least 30 min before taking food. (alen- and risedronate)

Question 2

Adverse effects of Bisphosphonates are:

Answer 2

• Atypical Femoral Fracture
• Osteonecrosis of the jaw / external auditory canal
• Severe bone, joint or muscle pain
• Ocular effects -> iritis, uveitis
• Hypo-Ca
• Gastrointestinal mucosa irritation

[Oral] N, abdo pain, heartburn
[IV] Flu-like Sx

Question 3

Contraindications for Bisphosphonates are:

Answer 3

1) GI abnormalities (eg. uncontrolled GORD, bariatric surgery)
2) Unable to sit / stand for 30 min.
3) Aspiration risk
4) Hypo-Ca
5) Hypersensitivity

Special Pop.:
CrCL < 30 ml/min
Pregnancy and Lactation

Question 4

What is the MoA of Denosumab?

Answer 4

Inhibits RANK Ligand (which is released by osteoblast to activate osteoclast).
Osteoclast is prevented from developing.

Question 5

Adverse effects of Denosumab are:

Answer 5

Muscle, back, bone, joint pain
N/V/C/D
Slight tiredness
Raised cholesterol

Risk of multiple vertebral fracture on sudden discontinuation.

Question 6

Contraindications for Denosumab are:

Answer 6

• Hypo-Ca
• Pregnancy

Question 7

What is the MoA of Raloxifene?

Answer 7

1) Oestrogen receptor agonism +
2) Oestrogen receptor antagonism

-> not used in menopause

Question 8

What are the benefits of Raloxifene (SERM) over Oestrogen?

Answer 8

Still has same effect on bone density.
Still has increased risk of thrombosis.
Still can cause hot flashes.

But reduces instead of increasing risk of breast cancer.

Question 9

What is the MoA of Calcitonin?

Answer 9

Secreted by parafollicular cells of the thyroid gland.
- reduces blood Ca
- Inhibits osteoclastic bone resorption.

Question 10

What is the possible routes of administration of Calcitonin?

Answer 10

IV, SC, IM or nasal spray

Question 11

Adverse effects of Calcitonin are:

Answer 11

Red streaks on skin
Injection site rxn
Feeling of warmth
Redness of the face, neck, arms, and (occasionally) upper chest

Question 12

Contraindications for Calcitonin are:

Answer 12

• Hypo-Ca
• Hypersensitivity

Question 13

What is the MoA of Romosozumab?

Answer 13

Humanized mouse mAb against Sclerostin.
- removes sclerostin inhibition of the canonical Wnt signalling that regulates bone growth.
- Increase bone formation and decrease bone resorption.

Question 14

Place in therapy for Romosozumab:

Answer 14

Women at high risk of fracture, OR
Failed, OR
are intolerant to other osteoporosis therapies.

Question 15

Adverse Effects / Contraindications for Romosozumab are:

Answer 15

Contraindications:
- Hypersensitivity
- Uncorrected hypo-Ca (because of potential hypo-Ca)
- Hx of MI or stroke (increased risk)

Other side effects:
- AFF
- ONJ

Question 16

What is the MoA of Parathyroid Hormone therapies given at intermittent, high doses?

Answer 16

• Stimulates new bone formation
• Increase bone strength

Question 17

What is the maximum treatment duration for PTH?

Answer 17

24 months in lifetime.
- potentially increased risk of osteosarcomas.

Question 18

Adverse Effects of PTH therapies are:

Answer 18

Serious calciphylaxis
Worsening of previous stable cutaneous calcification
Hyper-Ca
Transient orthostatic hypotension

Question 19

Contraindications of PTH therapies are:

Answer 19

• Hypersensitivity
• Pre-existing hyper-Ca
• Skeletal malignancies or bone metastases
• Metabolic bone diseases (eg. Paget’s disease, hyperparathyroidism)
• Unexplained elevations of ALP
• Had Skeletal implant / external beam radiation therapy to the skeleton
• Genetic predisposition to osteosarcoma.
• Severe RENAL impairment
• Pregnancy

Question 20

Target Serum Vitamin D levels for Osteoporotic patients are:

Answer 20

20-30 ng/ml (50-75 nmol/L)
but less than 50-100 ng/ml (125-250 nmol/L)

Question 21

What Non-Pharmacological advice is appropriate for an Osteoporotic patient?

Answer 21

• Exercise: 30 min daily weight-bearing, muscle-strengthening & balance (2-3 x weekly)
• Stop / reduce:
  1) Smoking
  2) Caffeine and alcohol (<= 2 cups/units per day)
• Reduce risk of falls
  1) Patient education
  2) interventions for impaired vision / cataract
  3) Footwear
  4) Home modifications
• Ca intake
  1) Supplement if dietary intake < 700mg / d
  2) Decreased Ca absorption w/: PPI, fibre.
  3) Decreased absorption of: Iron, tetracyclines, FQs, bisphosphonates, thyroid supplement.
• Vit D intake
  1) 800 IU / d
  2) Decreased Vit D levels: rifampin, anticonvulsants, cholestyramine, orlistat, Al-containing products.

Question 22

Monitoring parameters for osteoporotic treatment are:

Answer 22

• SCr
• Serum Calcium
• Serum 24(OH) Vitamin D

Question 23

What other lab tests can help to exclude secondary causes of bone loss?

Answer 23

• Erythrocyte sedimentation rate (ESR)
• ALP
• Serum phosphate
• Urine Ca/Cr ratio
• Serum total testosterone

Question 24

When should a patient be treated for Osteoporosis?

Answer 24

1) Presents w/ fragility #
2) No fragility #, but DXA BMD T-score <= 2.5
3) Osteopaenic and no fragility fracture, but w/ high # risk (FRAX >3% hip # risk or >= 20% major osteoporotic #)