Osteoporosis, osteomalacia and Paget's disease Flashcards
In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in osteoporosis?
All are at normal levels
- the matrix/mineral ratio is normal but the overall amount of bone is reduced
What is a T score?
Number of standard deviations from the mean BMD of a young (30) person of the same gender + ethnicity
- used more often than z score
What is a z score
Number of standard deviations from the mean BMD of a person of the same age, gender + ethnicity
What is a normal bone mineral density score? What score indicates osteopenia, and what indicates osteoporosis?
Normal: -1 –> +4
Osteopenia: -2.5 –> -1
Osteoporosis: = -2.5
What kind of bones are more susceptible to osteoporosis?
Bones with a high proportion of trabecular bone –> vertebral bodies, femoral neck
Explain the pathogenesis of osteoporosis.
- relative increase in bone resorption (not matched by formation)
- bone is mineralised as normal, there is just less bone
- bone loss is not evenly distributed
If a person is >75 and has a low trauma fracture, what action should be taken?
Give bisphosphonates, calcium and vit D
If a person is 50-75 and has a low trauma fracture, what action should be taken?
Refer for a DEXA scan
If a person is 65-75 and DEXA gives a T score < -2.5, what action should be taken?
Give bisphosphonates, calcium and vit D
If a person is 50-75 and DEXA gives a T score >-2.5, what action should be taken?
Give calcium and vit D
If a person is 50-65 and DEXA gives a T score < -3.2, what action should be taken?
Bisphosphonates, calcium and vitamin D
If a person is 50-65 and DEXA gives a T score -2.5 –> -3.2 + clinical risk factor(s), what action should be taken?
Bisphosphonates, calcium and vitamin D
Apart from Bisphosphonates, calcium and vitamin D, what other treatments can be given for osteoporosis?
- HRT (oestrogen replacement for post-menopausal; lasts ~5 years
- Raloixfene: selective oestrogen receptor modulator
- Teriparatide
- Denosumab
What is the MOA of bisphosphonates?
- Potent inhibitors of bone resorption - osteoclasts will not attach where bisphosphonates are present
- if osteoclasts do absorb bisphosphonates this will cause apoptosis
- increase OPG production + reduce RANKL production = reduce osteoclast differentiation
What complications are associated with bisphosphonates?
- giant osteoclasts
- osteonecrosis of the jaw (due to inhibition of osteoclasts)
- atypical fractures –> subtrochanteric + femoral shaft
- -> old osteocytes signal for remodelling but fewer good osteoclasts
What is the MOA of teriparatide?
- Intermittent exposure to PTH will activate osteoclasts, but exposure is not long enough to activate osteoclasts
- will not increase bone mass dramatically
What is the MOA of denosumab?
- subcutaneous injection every 6 months
- inhibits osteoclasts formation –> by binding to RANKL
In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in osteomalacia?
Ca2+: decreased PO4 3-: decreased Alkaline phosphatase: increased PTH: increased active vit D: decreased
Why does osteomalacia occur?
Usually a result of vitamin D deficiency
What is the main difference between osteomalacia in children and adults?
Children: more deformities as epiphyseal growth plate is open
Adult: less deformities epiphyseal growth plate is closed
What will imaging of osteomalacia?
pseudo fractures, areas of unmineralised bone
How can tetracycline used to diagnose osteomalacia?
give 2 pulses of tetracycline each for 3 days and each pulse is 10 days apart
Normal result: 2 distinct lines
Mild/moderate osteomalacia: diffuse or single labelling
Severe osteomalacia: no labelling –> no mineralisation taking place
What is the treatment for osteomalacia?
- vitamin D
- increase Ca2+ (dietary)
- sun or UV exposure
What are the 3 phases of Paget’s disease?
- Initiation phase:
- increased bone resorption
- large number of giant osteoclasts - compensatory/proliferation phased (mixed)
- increased bone formation
- accelerated deposition in disorganised manner - Burnt out phase
- bone hypercellularity may diminish = dense pagetic bone
- hypervascular bone marrow
- irregularly thickened trabeculae
- prominent cement lines
- bone marrow replaced by fibrovascular connective tissue
What bones are typically affected in Paget’s disease?
pelvis, femur, vertebrae, skull, tibia
What is a late complication of Paget’s that mostly occurs in young people?
Osteosarcoma –> rare (1%)
- among most malignant of cancers
What is used to treat Paget’s disease?
Bisphosphonates calcium + vit D pain management surgery calcitonin
What is Sclerostosis?
Also known as Van Buchem Syndrome
- caused by the absence/ reduced production of sclerostin
- autosomal recessive
- endosteal hyperostosis
- resistant to fracture
- excessive height
In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in Paget’s?
alkaline phosphatase is v high, everything else is normal
In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in renal failure?
Ca2+: reduced PO4 3-: increased Alkaline phosphatase: normal/high PTH: increased active vit D: decreased
In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in primary hyperthyroidism?
Ca2+: increased PO4 3-: reduced Alkaline phosphatase: normal/high PTH: increased active vit D: normal
