Bone Abnormalities Flashcards
What are the terms to describe too little or too much bone?
Osteoporosis
Osteopetrosis
Name 3 causes of defective bone mineralisation?
- Rickets
- Osteomalacia
- Hyperparathyroidism
Name 3 causes of a change in bone structure
- Osteogenesis imperfecta (collagen defect: loss of flexibility = brittle)
- Paget’s disease (rapid turnover due to overactive osteoclases = poor quality woven bone)
- tumours
How is bone structure assessed?
Blood tests
- calcium, phosphate, vitamin D, parathyroid hormone
- alkaline phosphatase, albumin
Imaging
- Plain X-ray
- Radionuclide scans (technetium, Tc)
- CT / MRI / ultrasound
Bone biopsy - histology
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Bone density
• DEXA (Dual Energy X-Ray Absorptiometry)
What is osteoporosis?
A complex skeletal disease characterised by low bone density and micro-archeitectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture.
Name some wider implications of osteoporosis
Future fractures
Pain
Quality of life
Long term admission
Mortality
Name risk factors for osteoporosis
- Old age
- Sex
- Ethnicity
- Low BMI
- Family hx
- Fragility fracture
- Post-menopausal
- Smoking
- Excessive alcohol use
- Steroids
- Immobility
- Vit D & Ca deficiency
Describe the pathophysiology of osteoporosis
- Loss of balance between bone formation & bone resorption during remodelling
- Osteoclasts make deeper holes
- Osteoblasts not as efficient
How is osteoporosis diagnosed by DEXA scan?
Normal: hip BMD greater than the lower limit of normal - 1 SD below the young adult reference mean- (T score ≥-1).
Low bone mass (osteopenia): hip BMD between 1 and 2.5 SD below the young adult reference mean(Z score). (T score less than -1 but above -2.5).
Osteoporosis: hip BMD 2.5 SD or more below the young adult reference mean (Z score) (T score ≤-2.5).
Severe osteoporosis: hip BMD 2.5 SD or more below the young adult reference mean in the presence of one or more fragility fractures (T score ≤-2.5 PLUS fracture).
Describe the management of osteoporosis
Diet
Exercise
Supplements
Fall prevention
Pharmacological treatment
- Oral/(IV) bisphosphonates
- SERMs
- PTH
- Denosumab
What is the first line treatment for osteoporosis?
Bisphosphonates
First line treatment: Alendronic acid (Alendronate), Risedronate, Zoledronic acid.
How do bisphosphonates work?
Slows the rate of bone remodelling
Absorbed onto the hydroxyapatite crystals (analogues of pyrophosphate) and slow down rate of bone remodelling (long half life). Taken up by osteoclasts and interfere with their function / attachment to bone. Inhibit mevalonate pathway or form toxic ATP analogues.
What are bisphosphonates used for
what are their side effects
Uses: Osteoporosis, Paget’s disease, hypercalcaemia of malignancy
Side effects: asymptomatic hypocalcaemia, general GI disturbance, oesophageal reactions, osteonecrosis, possible long term effects.
What are SERMs and how do they work
Selective estrogen receptor (ER) modulator: Raloxifene
Action: mixed antagonist/agonist function – tissue specific
Use: Osteoporosis
Does not stimulate uterine or breast tissue
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Usually prescribed for postmenopausal osteoporosis if bisphosphonates not tolerated
Describe PTH and its use in treating osteoporosis
Parathyroid hormone
Action: promotes bone production
Administration: SC injection
Side effects: hypercalcaemia, muscle cramp, nausea and vomiting
•Continuous PTH causes bone loss
•Intermittent peaks promote production trabecular bone (anabolic)
• Increase osteoblast differentiation and activity.
•¯ Decreaste osteoblast apoptosis and sclerostin
What is Denosumab and describe its use in the treatment of osteoporosis
Monoclonal antibody
Action: inhibits osteoclast formation, function and survival
Administration: SC injection
Side effects: hypocalcaemia, diarrhoea, dyspnoea, constipation
