Bone abnormalities Flashcards
Recap:
Major functions of bone
Types of bone
Cells involved in bone remodelling
Osteoid composition
What else do osteoblasts secrete?
How is bone remodelling regulated?
- Function of bone à support, movement, Ca2+ and phosphate homeostasis, protection
- Types of bone –> first woven, then lamellar bone (mature bone), two types of lamellar bone –> cortical and trabecular
- Cells involved in bone remodelling –> osteoblasts and osteoclasts
- Osteoid –> Type 1 collagen, proteoglycans, glycoproteins
- Osteoblasts secrete –> alkaline phosphatase, RANK ligand, Osteoprotegrin, osteocalcin (Binds Ca2+)
Regulation –> balance of OPG to RANKL, hormones PTH and oestrogen, interleukins, cytokines and age.
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Bone structure and function:
Describe main functions of bone as a metabolic tissue
Describe main functions of bone as a protective load bearing tissue
Metabolic tissue:
- Acts as a mineral buffer, largest stores of Ca2+
- Needs to be able to repair microfractures that occur throughout life to maintain quality of bone
- Coordination of bone cells (osteoclasts vs blasts) vital
Protective, load bearing:
- Cortical vs trabecular (weight vs strength)
- Rigidity and resilience (hydroxyapatite: Collagen)
What pathological changes can there be to bone?
- Change in the quantity of bone:
- too little –> osteoporosis, common
- too much –> osteopetrosis, uncommon, very bright on an xray
- Change in quality of bone:
- defective/ loss of mineralisation –> rickets/ osteomalacia/ hyperparathyroidism
- Change in the structure of bone:
- osteogenesis imperfecta --> collagen defect, loss of flexibility bones v brittle
- Paget’s disease –> rapid turnover due to osteoclasts, poor quality woven bone
- Tumours
What clinical tests are there to assess bone structure?
- Blood tests:
- PTH, Ca2+, Vitamin D
- Routine –> Alkaline phosphatase, albumin (nutritional status links to bone density)
- Imaging:
- plain X-ray
- Radionuclide scans –> inject radioactive substance which targets overactive cell (osteoblast/clasts)
- MRI/ CT/ Ultrasound
- Bone biopsy –> tumour
- Bone density –> DEXA scan (dual energy X-ray Absorptiometry)
What is osteoporosis?
What bones are most commonly fractured?
Osteoporosis = complex skeletal disease characterised by low bone density and microarchitectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture.
Common, affects 3,000,000 people in the UK, european and asian populations
Risk of fracture increases with Age, 1/2 for women, 1/5 for men, most common in post menopausal women
Bones most commonly fractured = neck of femur, vertebra and wrist
What damage can occur to the vertebral column with osteoporosis?
- Crush fracture e.g. left picture L4 is crushed
- Natural kyphosis of the thoracic vertebrae, with osteoporosis these vertebrae can become crushed, exaggerating the kyphosis giving a hunched over appearance
- Intervertebral foramina get smaller too, can lead to nerve impingement
What is the pathology shown?
- Left: Radial fracture and loss of ulnar styloid process, due to fall on outstretched hand
- Right: Left intracapsular femur neck fracture, risk of cut off blood supply and avascular necrosis
What are the wider implications of osteoporosis?
- Osteoporosis often picked up due to a fall and subsequent fracture
- Leads to a loss of confidence –> less exercise, lower bone density, slower reflexes and poor balance
- –> increased risk falls and fractures
- Pain
- Decreased QOL, permanent disability, lost independence
- Long term admission –> catch secondary infection/ AKI from surgery
- High mortality
What are some of the risk factors for osteoporosis?
Unmodifiable:
- Age/ postmenopausal woman
- Sex
- Ethnicity (european or asian)
- Family Hx
Modifiable:
- Immobility (wolffs law)
- smoking/ alcohol
- steroids
- vitamin D/ Ca2+ deficiency
- Low BMI
Describe the pathophysiology of osteoporosis
- After skeletal maturity we reach peak bone mass, which plateaus until older age, at which point skeletal bone density declines
- Declines faster in post menopausal women (rate of 2% per yr after menopause)
- Osteoporosis due to loss of balance of bone formation and bone resorption during remodelling
- Decline in number of osteoprogenitors and osteoblasts, decline in osteoblast efficiency
- Increase in RANKL and increase in osteoclast bone resorption
- Balance pushed towards bone loss, increased depth of holes created by osteoclasts
- Loss bone density, increased fragility and risk of fracture
What are the main screening tools used in osteoporosis?
What is secondary prevention?
- FRAX = evaluates the fracture risk of patients by taking into account their risk factors and past fractures which gives you a score
- Score may indicate a DEXA scan or may DEXA as a screen
- Secondary prevention may be indicated –> prevent further falls with mobiloty aids, supported living situation
What is DEXA?
What are possible DEXA scores?
- DEXA (Dual energy Xray absorptiometry)
- 2 xray beams are pointed at the patient with different levels of energy, soft tissue is subtracted away and it determines the bone density
- Gives two Scores Z score and T score (focus on T score)
- T scores relate to the mean bone density of a young adult and are given as standard deviations:
- BMD of less than 1 SD from young adult mean (T score ≥-1) = Normal
- BMD 1-2.5 SD below young adult mean (T score less than -1 but above -2.5) = osteopenia (may occur after fracture and immobility in healthy adult).
- BMD more than 2.5 SD below the young adult mean (T score less than -2.5) indicates osteoporosis.
- Note on scan below darker regions indicate low BMD, especially around femur neck.
How would you manage osteoporosis?
- Diet
- exercise
- supplements - vitamin D and calcium
- Fall prevention
- Pharmacy:
- oral bisphosphates
- SERMs
- PTH
- Denosumab
What pharmacological treatments can be used to treat osteoporosis?
- Bisphosphates –> alendronic acid/ Alendronate, risendronate, Zolendronic acid (1 /yr injection)
- SERM –> selective oestrogen receptor modulator –> Raloxifiene
- PTH
- Denosumab –> bind RANKL
Name 3 Bisphosphates and their administration
What is their mechanism of action
What diseases are they useful in treating?
What are their side effects
- Alendronic acid/ Alendronate, Risedronate (one day / week), Zoledronic acid (1/ yr injection).
- Must be on empty stomach, 1 glass water, remain upright for half an hour –> patients may resist but important to prevent erosion of oesophagus
- MOA:
- Absorbed onto the hydroxyapatite crystals which slows down rate of bone remodelling
- Taken up by osteoclasts interferes with ruffled border attachment to bone
- Osteoclasts unable to attach to bone, less enzymes released and less bone resorption
- Slows rate of bone remodelling
- Uses: Osteoporosis and Pagets disease, Hypercalcaemia of malignancy
- Side effects:
- asymptomatic hypocalcaemia
- general GI disturbance
- oesophageal reactions
- osteonecrosis of the jaw–> rare but be aware of dentition before treatment, in larger doses or zolendronic acid.
- possible long term effects –> atypical femoral fractures
Absorption and elimination:
- Poorly absorbed; absorption ¯ if taken with Ca2+
- Not metabolised, excreted unchanged in urine (caution in CKD)
What antibody treatment can be used in osteoporosis?
What is its MOA
Administration
SE’s
- Denosumab = monoclonal antibody directed against RANKL
- Mimics the natural decoy receptor osteoprotegerin and binds to RANKL, inhibiting RANKL stimulation of osteoclasts prevent bone resorption
- Administration : SC injection
- SE’s: hypocalcaemia, diarrhoea, dysponea and constipation
What are three key pathological features with rickets?
- Growth retardation
- bony deformities
- imaging shows widening/ splaying of the epiphyseal growth plate/ metaphysis
What different types of bone cancer can be seen?
- Primary vs secondary bone cancers:
- primary bone cancer is when the cancer has arisen from within bone tissue
- this is very rare
- secondary cancer is more common and is where another cancer has metastasised to the bone
- often prostate, breast and lung cancers
- Benign vs malignant:
- benign bone cancer –> osteoma or chondroma
- malignant bone cancer –> osteosarcoma or chondrosarcoma
- Lytic vs sclerotic:
- When bone is invaded by metastatic cells it often causes two types of lesions depending on the primary cancer
- In breast and lung –> often see lytic lesions, where bone is broken down and replaced with cancer tissue, often see hypercalcaemia
- In prostate cancer –> tends to stimulate bone growth that is unstructured woven bone. This becomes mineralised and forms a sclerotic lesion.
- Often affects surrounding tissues.
What is Paget’s disease?
what is the pathophysiology and what type of lesions can be seen?
What bones may it affect?
What is its occurence?
- Pagets disease is characterised by increased bone turnover with overactive osteoclasts which resorb bone very quickly –> lytic lesions
- Osteoblasts react by laying down unstructured poor quality woven bone that does not get remodelled –> sclerotic lesions
- woven bone is weak
- results in overgrowth, bowing, pain, fractures and deformity
- May be focal or multifocal
- It can affect the skull and its foramina, may present with cranial nerve palsy, e.g. visual disturbance or hearing loss
- Estimated to occur in 1-3% of people over 55 yrs
Note the changes in the following xray and bone scan, describe them
Distal humerus has lost its structure v susceptible to fracture
Radionuclide scan showing high activity in L femur
What is osteogenesis imperfecta?
- Osteogenesis imperfecta = group of disorders charactersied by defective production and processing of type 1 collagen due to genetic mutation in collagen genes
- Two forms type 1 osteogenesis imperfecta mildest form, may have multiple fractures but no deformity
- Type 2 is a severe form with very brittle bones that may fracture during labour and during breathing, kyphoscoliosis which restricts breathing.
- It is a systemic disease:
- brittle bones
- 50% may have hearing loss
- Sclera may appear blue, purple or grey (thin collagen allowing you to see vasculature underneath).
- Often problems with teeth (brown tint)
- Growth retardation
