Pathology - Fractures Flashcards
Mechanism of Action of Bisphosphonates?
Increases osteoclast cell death
Examples of Bisphosphonates?
Risedronate or alendronate (oral); Zoledronic acid (IV)
ADME of bisphosphonates?
Oral bisphosphonates on empty stomach with at least 240ml of water; wait before taking food (30min)
Adverse effects of bisphosphonates?
Significant: Atypical femoral fractures (prolonged use), severe bone, joint or muscle pain; Upper GI mucosa irritation; ocular effects (iritis, uveitis), hypocalcemia; osteonecrosis of jaw & external auditory canal
Oral: Nausea, Abdominal Pain, Heart-burn like symptoms
IV: Flu-like symptoms
Contraindications of bisphosphonates?
Hypocalcemia; abnormalities of esophagus; renal impairment; pregnancy & lactation
Precautions in bisphosphonates?
Active Upper GI, Risk Factors for Osteonecrosis of Jaw & External Auditory Canal
Mech of Action Denosumab?
Human Monoclonal Antibody vs RANKL = Less development of osteoclasts
Administration of Denosumab?
- SubCU injection every 6 m
- Co-administer 1000mg calcium + 400 IU vitamin D daily
Adverse Effects of Denosumab?
- Muscle, Back, Bone or Joint Pain
- GI effects - nausea, vomitting, diarrhoae
- Fatigue
- Increased cholesterol
- Osteonecrosis of Jaw (rare)
- Atypical Femur Fractures (rare)
Contraindications for Denosumab?
Hypocalcemia, Pregnancy
Precautions for denosumab?
Do not discontinue as may cause risk of spinal column fractures
Oestrogen therapy mechanism of action?
Maintain bone density
Uses of oestrogen therapy?
i) bone health in younger women
ii) women whose other menopausal symptoms also require treatment
Mechanism of Action of Raloxifene?
Selective oestrogen receptor modulator: mixed oestrogen receptor agonism and antagonism, mimicking effects of oestrogen on bone density in post menopausal women
Adverse Effects of Raloxifene?
Increase risk of blood clots, cause hot flashes
Advantage of Raloxifene?
Reduces risk of some types of breast cancer
Calcitonin mechanism of action?
Secreted by parafollicular cells of thyroid gland, reduces blood calcium, inhibiting osteoclastic bone resorption (opposed action of PTH)
Administration of calcitonin?
injection (IV, SC, IM) or nasal spray
Adverse Effects of calcitonin?
Red streaks on skin
Injection site reaction
Feeling warmth
Redness of face, neck, arms and upper chest
Contraindications of Calcitonin?
Hypersensitivity, hypocalcemia
Mechanism of Action of Romosozumab?
Humanized mouse monoclonal antibody against sclerostin; removes sclerostin inhibition of the canonical Wnt signaling pathway that regulates bone growth = increasing bone formation and decreases bone resorption
Uses of Romosozumab?
For women at high risk of fracture or who have failed or are intolerant to other osteoporosis therapies
Administration of Romosozumab?
Subcu injection once monthly for 12m
Adverse Effects of Romosozumab?
Significant: MI, Increase risk of CV death, stroke; transient hypocalcemia, hypersensitivity reactions (angioderma, erythema multiforme, urticaria, dermatitis, rash)
Rare: Osteonecrosis of Jaw, Atypical femur fractures
Contraindications of Romosozumab?
Hypersensitivity, uncorrected hypocalcemia, history of MI or stroke
Mechanism of Action of PTH therapy (parathyroid hormone similars - e.g. teriparatide)
PTH action, stimulates new bone formation and increases bone strength
Administration of Teriparatide?
Once daily SC injection
Precautions of Teriparatide?
Maximum treatment duration 24m in life time (increases risk of osteosarcomas)
Adverse Effects of Teriparatide?
- Serious calciphylaxis
- Worsening of previously stable cutaneous calcification
- Transient Orthostatic Hypotension
- Hypercalcemia
Contraindications of Teriparatide?
- Hypersensitivity
- Pre-existing hypercalcemia
- skeletal malignancies or bone metastases
- other metabolic bone diseases (Paget’s, Hyperparathyroidism), 5. unexplained elevations of alkaline phosphatase
- previous implant or external beam radiation to the skeleton
- hereditary disorders predisposing to osteosarcoma
- severe renal impairment
- pregnancy
