Bone Abnormalities Flashcards
What are the functions of bone as a metabolic tissue?
- Acts as mineral buffer
- Needs to be able to repair damage and maintain integrity
- Quality of bone
- Coordination between bone cells
What are the protective and load-bearing functions of bone?
- Cortical versus trabecular bone = weight versus strength
2. Rigidity:resilience = hydroxyapatite:collagen
Why can fractures occur?
- Too much force
2. Problem with the bone
What is osteogenesis imperfecta?
Group of disorders characterised by defective production (processing) of type I collagen due to genetic mutations in collagen genes leading to loss of bone flexibility making bones brittle which is why it is called BRITTLE BONE DISEASE
What is Pagets disease?
When there is rapid turnover of overactive osteoclasts so there is poor quality woven bone
What blood tests can be done to assess bone structure?
Routine: ALP + albumin
Others: Ca2+, phosphate, vitamin D + PTH
What imaging can be done to assess bone structure?
- Plain X-ray
- Radionuclide scans: radioactive material e.g. technetium (Tc) is put into body to pick up an overactive cell type
- CT/MRI/US
How should we assess bone structure?
- Blood tests
- Imaging
- Bone biopsy (histology)
- Bone mineral density (BMD) via a Dual Energy X-ray Absorptiometry (DEXA) scan
What problems with the bone can cause fractures?
- Quantity of bone:
- Too little bone (osteoporosis)
- Too much bone (osteopetrosis) - Quality of bone:
- Defective/loss of mineralisation (rickets, osteomalacia or hyperparathyroidism)
- Change in structure (osteogenesis imperfecta, Paget’s disease or tumours)
What is osteoporosis?
A complex skeletal disease, most common in post-menopausal older women, characterised by low bone density and micro-architectural defects in bone tissue resulting in increased bone fragility and susceptibility to fracture esp. of the neck of femur, vertebral bodies and wrist
What does FOOSH stand for?
Fall On OutStretched Hand
Why do some older adults demonstrate a hunched-over appearance?
The natural lumbar kyphosis can become exaggerated as the intervertebral (IV) discs become compressed and smaller (can impinge nerves too)
What are the wider implications of osteoporosis?
Future fractures Pain QoL Loss of confidence Long-term admission Permanent disability Mortality
What are the risk factors for osteoporosis?
Old age Sex (females > males) Ethnicity Low BMI Family Hx Fragility fracture Post-menopausal Smoking Excessive alcohol use Long-term steroid use Immobility Vit D + Ca2+ deficiency Etc...
When are patients most commonly assessed for osteoporosis?
If an elderly patient has had a fall and a fracture
What is the pathophysiology of osteoporosis?
- Genetic factors, nutrition and physical activity make up an individuals peak bone mass
- During aging, there is:
- Decreased replicative activity of osteoprogenitor cells
- Decreased synthetic activity of osteoblasts
- Decreased biologic activity of matrix-bound GFs
- Reduced physical activity - During menopause there is:
- Decreased serum oestrogen
- Increased IL-1, IL-6 + TNF levels
- Increased expression of RANK + RANKL
- Increased osteoclast activity - Balance disruption between bone formation and resorption due to decreased osteoblast activity and increased osteoclast activity cause a net bone loss = osteoporosis
When does peak bone mass deteriorate?
Men: achieve a higher peak bone mass that plateaus and gradually declines at around 50 years old
Women: peak bone mass deteriorates rapidly post-menopausal
What can be done for fracture patients?
- Secondary prevention of injury e.g. home changes
- FRAX tool to evaluate fracture risk
- DEXA scan if indicated by the FRAX tool and other factors to diagnose osteoporosis clinically
How is osteoporosis diagnosed?
DEXA scan that outputs a T-score:
- Normal = hip BMD < 1 SD below young adult mean (T-score equal to/> -1)
- Osteopenia = hip BMD 1-2.5 SDs below young adult mean (T-score < -1 but > 2.5)
- Osteoporosis = hip BMD 2.5 SDs or > below young adult mean (T-score fragility fractures
How do you manage osteoporosis?
Diet Exercise Supplements Fall prevention Pharmacological treatment
What pharmacological treatments are used to treat osteoporosis?
- Oral/IV bisphosphonates (1st line): Alendronic acid (Alendronate), Risedronate + Zoledronic acid
- SERMs: Raloxifene
- PTH: recombinant fragment of PTH e.g. Teriparatide (Forteo) SC injection
- Denosumab: SC injection
How do bisphosphonates work?
Primarily:
1. Absorbed onto hydroxyapatite crystals and slow rate of bone remodelling as they are taken up by osteoclasts and interfere with their function by reducing their attachment to bone via their ruffled surface meaning that they do not release acids/enzymes to resorb bone
Some:
2. Inhibit mevalonate pathway or form toxic ATP analogues
3. Decrease osteoclast progenitor development/recruitment
4. Promote osteoclast apoptosis
Used orally most commonly (OD/OW) in osteoporosis, Pagets disease, hypercalcaemia or malignancy
Why are the side effects of bisphosphonates?
- Asymptomatic hypocalcaemia
- Oesophageal reactions + general GI disturbance (patients need to take it in morning on empty stomach with a glass of water + sit up for a while = unpopular)
- Osteonecrosis of jaw
- Possible long-term effects e.g. atypical femur fracture
What considerations must be taken into account when prescribing bisphosphonates?
- Poorly absorbed and absorption decreased if taken with Ca2+
- Not metabolised but excreted unchanged in urine so must be given with caution in patients with CKD
- Patients dental hygiene if giving big doses e.g. Zoledronic acid as osteonecrosis of jaw can occur in rare cases
How do Selective Estrogen Receptor (ER) Modulators (SERMs) work?
Mixed antagonist/agonist function that is tissue specific: antagonist of uterine/breast tissue but agonist in bone so there is no cancer risk but treatment of osteoporosis - used commonly in postmenopausal osteoporosis if bisphosphonates not tolerated
How does Parathyroid Hormone (PTH) work?
Intermittent peaks (doses) promote production of trabecular bone (anabolic) by:
- Increasing osteoblast differentiation and activity
- Decreasing osteoblast apoptosis and secretion
But continuous PTH will cause bone loss so max duration of treatment is 24 months
What are the side effects of Parathyroid Hormone (PTH)?
Hypercalcaemia
Muscle cramp
N+V
How does Denosumab work?
Monoclonal Ab acts like OPG as a natural decoy for RANKL mopping it up decreasing formation, function, activation and survival of osteoclasts subsequently slowing down bone remodelling and resorption
What are the side effects of Denosumab?
Hypocalcaemia
Diarrhoea
Dyspnoea
Constipation
What are rickets and osteomalacia?
Disorders characterised by inadequate mineralisation of bone where bone remains as chrondrocytes instead of being mineralized to bone so they have the SAME pathological process, depending on whether or not growth plates are fused, but DIFFERENT manifestations - most common cause if vitamin D deficiency usually resulting low Ca2+ and phosphate levels
What is the difference between rickets and osteomalacia?
Rickets: defective mineralisation at the GROWTH PLATE so affects CHILDREN
Osteomalacia: defective mineralisation of OSTEOID so affects ADULTS as well as CHILDREN
What are the signs and symptoms of rickets?
Growth retardation
Bony deformities
Fractures
Widening/splaying of epiphyseal growth plate/metaphysis (as shown by imaging)
What are the signs and symptoms of osteomalacia?
May be asymptomatic
Muscle weakness (proximal)
Bone pain
Fractures
How should you test for rickets and osteomalacia? What is the treatment?
Blood test: vitamin D, Ca2+ and phosphate will be low whereas ALP will be high
Management: DEXA scan/X-ray by specialist but mostly education, diet advice and supplements
What types of bone cancers exist?
- Primary: arisen from bone tissue (rare)
- Secondary: metastasis from breast, lung or prostate cancers for example as bone has a good blood supply
Which can both be either benign or malignant
How can you tell what cancer might have metastasized to the bone?
Lytic lesions: bone will be less dense and more translucent on X-ray as bone has been broken down and replaced by tissue from cancer e.g. breast or lung - release of Ca2+ too (hypercalcaemia)
Sclerotic lesions: woven bone production is stimulated but this is unstructured so you get dense bone appearing more opaque and bright on X-ray e.g. prostate cancer
What is Paget’s disease of the bone?
Disease characterised by increased bone turnover as osteoclasts are overactive due to genetic/environmental factors so osteoblasts start to react by laying down more weak woven (immature) bone resulting in overgrowth, bowing, pain, fractures, deformity and even visual/hearing disturbances if skull is affected (focal or multifocal lytic AND sclerotic lesions) - occurs in 1-3% of > 55 year olds
How do you investigate Paget’s disease?
- Bloods: serum Ca2+, PTH and ALP - ALP will be only high result
- X-rays
- Radionuclide bone scans to look for overactive osteoclasts
- Bone biopsy if malignant change is suspected as patients are more susceptible to mutations due to high bone turnover so need to be reviewed regularly - rapid growth and erythema can indicate malignancy
How do you treat Paget’s disease?
- Walkers, sticks and orthotics
- Analgesia if required
- Supplements
- Bisphosphonates: decrease OC recruitment and cause OC apoptosis decreasing depth of resorption site which in turn calms down osteoblasts
- Surgery
What are the symptoms of osteogenesis imperfecta?
Systemic disease:
- Brittle bones -> multiple fractures
- Hearing loss
- Sclera may have a blue, purple or grey tint (collagen so thin vascular underneath can be seen)
- Teeth problems i.e. brownish teeth
- Growth retardation
What are the different types of osteogenesis imperfecta?
Type 1: mildest form where patients can live their life but more susceptible to fractures
Type II: more severe where bones are so brittle they fracture during labour giving babies severe kyphosis that can restrict respiration so they only live for a few weeks after birth if they survive birth
What can osteogenesis imperfecta often get confused for?
Child abuse as the child may have multiple fractures in many limbs all at different stages of repair
What is the treatment for osteogenesis imperfecta?
No cure but it can be helped with:
- Braces
- Orthotics
- Surgery
- Bisphosphonates to stabilise bone remodelling process
