Ageing and Metabolic Bone Conditions Flashcards
what does osteoporosis serum results look like
- calcium
- phosphate
- alkaline phosphatase
- PTH
- 1,25(OH)2 Vitamin D
- calcium = normal
- phosphate = normal
- alkaline phosphatase= normal
- PTH = normal
- 1,25(OH)2 Vitamin D = normal
What does osteomalacia serum results look like
- calcium
- phosphate
- alkaline phosphatase
- PTH
- 1,25(OH)2 Vitamin D
- calcium = decrease
- phosphate = decrease
- alkaline phosphatase = increase
- PTH = increase
- 1,25(OH)2 Vitamin D = decrease
What does paget’s serum results look like
- calcium
- phosphate
- alkaline phosphatase
- PTH
- 1,25(OH)2 Vitamin D
- calcium = normal
- phosphate = normal
- alkaline phosphatase = double increase
- PTH = normal
- 1,25(OH)2 Vitamin D = normal
What does renal failure results look like
- calcium
- phosphate
- alkaline phosphatase
- PTH
- 1,25(OH)2 Vitamin D
- calcium = decrease
- phosphate = increase
- alkaline phosphatase = normal and increase
- PTH = increase
- 1,25(OH)2 Vitamin D = decrease
What does primary hyperparathyroidism look like
- calcium
- phosphate
- alkaline phosphatase
- PTH
- 1,25(OH)2 Vitamin D
- calcium = increase
- phosphate = decrease
- alkaline phosphatase = normal and increase
- PTH = increase
- 1,25(OH)2 Vitamin D = normal
what produces alkaline phosphatase
= produced by osteoblasts and liver
decrease what happens to the bone in osteoporosis
- the ratio between unmineralised and mineralised bone remains the same
- more bone is reabsorbed and less bone is made therefore there is less bone
describe what happens to the bone in osteomalacia
- increase in the amount of unmineralised matrix
describe what happens to the bone in a mixture of osteoporosis and osteomalacia
- have less overall amount of bone and more unmineralised bone
- common to have a co-mordbity of them
who is osteoporosis more prevalent in
women
what age do both men and women lose bone mass from
- both lose bone mass from age 40 onwards
- 0.7% a year
when does women bone loss speeds up
In women bone loss speeds up after menopause
2-9% a year
how do you measure bone mineral density
T or Z score from the DEXA scan
What is the T score
number of standard deviations from the mean young (30 yr) same gender and ethnicity
What is the Z score
number of standard deviations from mean aged, same gender and ethnicity
why do women get osteoporosis after menopause
- loose oestrogen which is protective
- oestrogen inhibits osteoclasts and increases the amount of calcium that is absorbed across the gut
what does DEXA scan stand for
dual energy X ray absorptiometry
- results show as a T and Z score
What are DEXA scans used for
- to look a bone mineral density
- when you have a fracture from a low force
what are the T scores of osteopenia between
1 and -2.4
what are the T scores for osteoporosis
Osteoporosis T scores below -2.5
what is the prevalence of osteoporosis in 50 and 80 years old
2% at 50 years
Greater than 25% at 80 years
what does osteoporotic bone looks like
- Bones with a high proportion of trabecular bone more susceptible to osteoporotic bone loss
- bigger gaps between
What two bones are commonly affected by osteoporosis
- vertebral bodies
- femoral neck
what is a compression fracture
- this is when there is a completely collapsed vertebrae body
- due to the weight of the body causing the thin network of fine trabecular to collapse and break
what is the underlying cause of osteoporosis
Relative increase in resorption not matched by formation
In osteoporosis what bone is particularly at risk to loss
Trabecular bone
- greater surface area (10x more surface area)
- this type of bone is in locations that has to respond to new stresses
- once you have thin trabecular you haven’t got the osteoblasts lined up to replace the damaged bone
What does osteoporotic bone look like
- Cortices and trabecular is thinned
- Osteoid seams are normal (approximately 20% of unmineralised osteoid)
what part of the vertebrae is particularly affected by compression fractures
cervical
how many people does compression fractures of the vertebrae affect
2 million postmenopausal women in England and Wales
180,000 fractures a year
describe the osteoporosis treatment pathway
- if they are over 75 and have a low trauma fracture then start the patient on bisphosphonate, calcium and vitamin d
- if they are between the age of 50-75 and have had a low trauma fracture refer for a dexa scan
Dexa scan results
- aged 50-65, and the T score is less than -3.2 then start on bisphosphonate, calcium and vitamin D
- if aged 50-65 and the T score is between -2.5 and -3.2 and there is a clinical risk factor then start on bisphosphonate, calcium and vitamin d
- if aged 50-75, and the T score is greater than -2.5, start on calcium and vitamin D
- if age 65-75, and T score is less than -2.5 then start on bisphosphonate, calcium and vitamin D
list some treatments that you can use to treat osteoporosis
- calcium supplements in order to reduce negative calcium balance
- vitamin D
- HRT - oestrogen replacement in perimenopausal women - lasts for 5 years
- selective oestrogen receptor modulator (raloxifene)
- Bisphophonates
- Teriparatide - rPTH
- denosumab - monoclonal antibody binds to RANKL
How does raloxifene work
- Selective oestrogen receptor modulator that has estrogenic actions on bones and anti-estrogenic actions on the uterus and breast
- prevents osteoporosis in post menopausal women
- not recommended as a primary treatment to prevent OP
How does bisphophonates work
- inhibit bone reabsorption
- they inhibit osteoclast activity and promote osteoclast apoptosis
- increases OPG production
- decreased RANKL expression
By how much does bisphophonates reduce fracture risk by
- reduces fracture risk by 50%
What are the complications of bisphosphonates
- Giant osteoclasts
- osteonecrosis of the jaw - dead bone is not removed and replaced with new bone
Atypical fractures
- subtrochanteric and femoral shaft
- old osteocytes signal for remodelling but fewer good osteoclasts
how does teriparatide work
Intermittent exposure to PTH will activate osteoblasts more than osteoclasts therefore causing more bone production then reabsorption
How does denosumab work
FDA approval June 2010, NICE October 2010
Subcutaneous injection every 6 months
binds to RANKL and inhibits it therefore Inhibits formation of osteoclasts
What is osteomalacia due to
Usually result of vitamin D deficiency either in diet or production
what happens in osteomalacia
- insufficient calcium and phosphate to mineralise new bone osteoid
who is osteomalacia more deforming in and why
In children the epiphyseal growth plate still open
= more deforming
In adults epiphyseal growth plate closed
= less deforming
what are the lab results for osteomalacia
Low serum calcium and phosphorus
High alkaline phosphatase
what is osteomalacia called in childhood
rickets
what is a sign of rickets and why does this occur
- bowed legs
- children have open epiphyseal growth plates, these widen and spread out
what are pseudo fractures
- these look like fractures but they are not
- they can progress to insufficiency fractures
- areas of unmineralised bone
- form at areas of higher bone turnover
what is the percentage of normal unmineralised osteoid
Normal bone unmineralised osteoid is around <20%
describe what osteomalacia looks like
- wide seems of unmineralised osteoid
- in severe cases up to 100% of bone is covered by unmineralised osteoid
- active osteoclasts increased
describe unmineralised osteoid
Must be greater than 80% of the total bone surface covered by osteoid
Osteoid thickness must be greater than 14μm
What happens in osteomalacia
- low bone turnover state
What does tetracycline look like in osteomalacia
Some areas have no tetracycline labelling
Some areas diffuse labelling suggestive of the altered mineralization
Some have a single line
What are the treatments of osteomalacia
- Vitamin D supplements - may need to take these for the rest of your life if you have liver or kidney failure
- increase calcium
- sun and UV exposure
what foods have calcium in them
Milk bread beans and pulses dried fruit green leafy vegetables!
how much sun or UV exposure should you have
15 mins of sun on hands and face 2-3 times a week in spring and summer is sufficient
What is the prevalence of Paget’s disease
Rare <40 years
3% of population >50 years
10% of population >80 years
How many phases of Paget’s disease are there
3
What are the three phases of Paget’s disease
phase 1
- initial increase rate of bone reabsorption and there is a large number of giant osteoclasts
- they remove a lot of bone this leads to osteoblast becoming more active
phase 2
- compensatory phase/proliferative
- increase bone formation
- acclearated deposition in disorganised manner
- lots of woven bone being laid down
phase 3
- burnout phase/sclerotic
- bone hypercellularity may diminish leaving paretic bone
- hypervascular bone marrow
what does Paget’s disease look like
Irregular thickened trabeculae
Prominent cement lines
Bone marrow replaced by fibrovascular connective tissue
trabecular is filled in so looks like cement
what does Paget’s disease look like physically
- bells palsy
- causes hearing problems
what are bones are commonly affected in Paget’s disease
pelvis femur vertebrae skull tibia
what is a rare complication of Paget’s disease
Osteosarcoma - 1% of cases
who does osteosarcoma usually occur in
the young
describe osteosarcoma
- among the most malignant of cancers
- usually in the long bone and often near the knee
- spread rapidly to the lungs
How do you prevent spread of osteosarcoma
- removal of part of the affected bone
- limb amputation
How do you treat Paget’s disease
bisphosphonates
- works directly on osteoclasts to slow bone reabsorption
- oral 2-6 months
- IV single infusion to 3 infusions
- calcium and vitamin D supplements
- pain surgery
- surgery
- calcitonin used less than bisphopshonates
what is scerltosis (van buchen syndrome)
Associated with absence or reduced production of sclerostin
what does sclerotin do
Secreted by healthy osteocytes
Normally inhibits osteoblasts to prevent excessive bone formation
Describe what sclerostosis do
Autosomal recessive
Endosteal hyperostosis
Resistance to fracture
Excessive height
what could blocking sclerotin do
used for osteoporosis