Bone Disorders Flashcards
What disease is characterised by a low bone mass causing skeletal fragility and susceptibility to fracture?
Osteoporosis
At what distinct sites does bone undergo remodelling?
bone remodelling units
What percentage of the adult skeleton is remodelled each year?
~10%
Briefly describe the bone remodelling cycle
- osteoclasts appear on a previously inactive surface
- resorb the bone
- replaced by osteoblasts in the cavity
- they put down osteoid that is mineralised to form new bone
Describe the ratio of osteoclasts to osteoblasts in osteoporosis
Osteoclasts>osteoblasts
=> more bone breakdown than formation
Describe the differences in micro-architecture between normal and osteoporotic bone
Osteoporotic:
- clear loss of bone
- large spaces and breaks
- breaks lead to weakened bones and fractures
Normal bone:
- thick, dense network
- small spaces
=> increased bone strength
At what age do humans achieve their peak bone density?
Late 20s
Menopause causes slower age related bone loss. TRUE/FALSE?
FALSE
Menopause causes a period of accelerated bone loss
What are the most common fracture sites in osteoporosis?
Neck of femur
Vertebral body
Distal radius
Humeral neck
An older lady with osteoporosis falling onto an outstrectched hand is most likely to sustain what type of fracture?
Colles fracture
Wedge fractures of the spine can result in what curvature forming?
Thoracic Kyphosis
What scan is used to measure bone density?
DEXA scan
What bones are measured in a DEXA scan to assess bone density and why?
Hip
L1-L4
- as these are most prone to fracture -
Describe the difference between a T score and a Z score on the DEXA scan
T score = bone density compared to young adult population average
Z score = compared to population average of the same age as the patient
In what situation would only a Z score be considered ni a DEXA scan?
If the patient was <20 years old
How are DEXA results interpreted?
Normal if less than 1 standard deviation (SD) below the young adult average
Osteopenia if between 1 and 2.5 standard deviations below the young adult average
Osteoporosis if 2.5 or more standard deviations below
What does 1 standard deviation of seperation in a DEXA scan indicate in terms of fracture risk?
Lowering by 1 SD doubles fracture risk
What type of patients should be referred for a DEXA scan?
> 50 with low trauma fracture
If at increased risk:
e.g. > 10% risk of fracture over 10 years
What calculators are used to measure fracture risk in osteoporosis?
FRAX or Qfracture
The new SIGN guideline is no longer based on treating patients in terms of their mineral bone density. What is it more concerned about?
Fracture Risk
Give an example of a risk factor for a fragility fracture that is non-modifiable
- Age
- Gender
- Ethnicity
- Previous #
- FHx
- Menopause ≤ 45 years
What risk factors for fragility fractures are modifiable?
- BMD
- Alcohol
- Weight/Physical inactivity
- Smoking
- Drugs (e.g. steroids)
What biochemical investigations should be considered in a patient who you are suspecting has osteoporosis
U+Es
LFTs
FBC and Plasma Viscosity
TSH
Consider:
- Coeliac antibodies
- 25OH Vitamin D
- Parathyroid hormone
What endocrine conditions are secondary causes of osteoporosis?
hyperthyroidism
hyperparathyroidism
Cushing’s disease
What GI conditions cause secondary osteoporosis?
coeliac disease
IBD
chronic liver disease
chronic pancreatitis
What respiratory conditions are linked to the development of secondary osteoporosis?
CF
COPD
What lifestyle advice is used in management of osteoporosis?
- High intensity strength training
- Low-impact weight-bearing exercise
- Avoidance of excess alcohol/smoking
- Fall prevention
How much calcium should post-menopausal women aim to eat per day in order to reduce their fracture risk?
1000 mg calcium (3-4 portion calcium rich foods)
What non-dairy foods are considered sources of calcium?
Non-dairy sources include
- bread and cereals (fortified)
- fish with bones, nuts,
- green vegetables, beans
What drug treatments are often given in osteoporosis?
- Calcium & Vit D supplements
- Bisphosphonates
- Denosumab (monoclonal antibody)
- Teriparatide (Parathyroid hormone anabolic agent)
- HRT
- SERMS (Selective Estrogen Receptor Modulators)
- Testosterone
How far apart should patients be taking their oral bisphosphonates and their calcium supplements?
Calcium supplements should not be taken within 2 hours of oral bisphosphonates
Give examples of Bisphosphonates
alendronate
risedronate
How do bisphosphonates work?
They are ingested by osteoclasts
cause cell death
=> restoring Osteoclast:osteoblast ratio
How long should patients remain on bisphosphonates?
benefit for 5 years (10 y if vertebral fracture)
Patients may also benefit from a period of no bisphosphonates
What complications may present if patients remain on Bisphosphonates long term?
osteonecrosis of the jaw
oesophageal Ca
atypical fractures
How is Zoledronic Acid administered?
- Once yearly IV infusion for 3 years
- 5 mg in 100 ml NaCl over 15 mins
- *can cause acute phase reaction on first infusion**
How does Denosumab work?
Monoclonal Antibody
inhibits development and activty of osteoclasts
=> prevents bone resorption
How is Denosumab administered?
Subcutaneous injection 6 monthly
What are the adverse effects of Denosumab?
Hypocalcaemia
eczema
cellulitis
Teriparatide mainly aims to stimulate bone growth rather than reduce bone loss. TRUE/FALSE?
TRUE
Describe the direct and indirect effects of corticosteroids on bone
DIRECT:
- Reduce osteoblast activity and lifespan
- Suppress replication of osteoblast precursors
- Reduce Ca absorption
INDIRECT:
- Inhibit gonadal and adrenal steroid production
What areas of the body do glucocorticoids act upon?
Bone
Kidney
Gut
Pituitary
Describe the activity of both osteoclasts and osteoblasts in Paget’s disease
Abnormal osteoclastic activity
increased osteoblastic activity
Describe the structure of bone developed in Paget’s disease
Abnormal bone structure with reduced strength and increased fracture risk
Can Paget’s disease present in more than one site?
Yes
- single site (monostotic)
- multiple sites (polyostotic)
What areas of bone are most affected by Paget’s disease?
long bones
pelvis
lumbar spine
skull
How does Paget’s disease usually present?
bone pain
deformity
deafness
compression neuropathies
What condition is a rare complication of Paget’s disease?
Osteosarcoma
What scan can be used to show the distribution of Paget’s disease?
isotope bone scan
If the pain in Paget’s disease does not respond to analgesia, what medication can be used?
Bisphosphonates
What complications can patient’s develop in Paget’s disease?
Bowing of femur/tibia
Deaf if skull involvement
curved spine
What genes are associated with the development of Paget’s disease and what do the encode?
mutations of type 1 collagen genes
COL1A1
COL1A2
How is Paget’s disease inherited?
Autosomal Dominant Inheritance
What other clinical signs are noted in severe forms of Osteogensis Imperfecta?
blue sclerae
dentinogenesis imperfecta
Describe the difference in age of presentation of mild to severs osteogenesis imperfecta
Mild - May not present until adulthood
Severe - usually present in childhood due to fractures having already occurred
What treatments are used in Osteogenesis Imperfecta?
- fracture fixation
- surgery to correct deformities
- bisphosphonates
What differential diagnosis should always be considered in a child presenting with a fracture that you think may be OI?
Non-accidental Injury
