Metabolic Bone Conditions and Ageing Flashcards
What can be seen in the serum blood results in osteomalacia? Calcium Phosphate Alkaline phosphatase PTH 1,25 (OH)2 vitamin D
Decreased Decreased Increased Increased Decreased
What can be seen in the serum blood results in Paget's? Calcium Phosphate Alkaline phosphatase PTH 1,25 (OH)2 vitamin D
All normal apart from alkaline phosphatase which is VERY high.
What can be seen in the serum blood results in renal failure? Calcium Phosphate Alkaline phosphatase PTH 1,25 (OH)2 vitamin D
Decreased Increased Normal to high Increased Decreased
What can be seen in the serum blood results in primary hyperparathyroidism? Calcium Phosphate Alkaline phosphatase PTH 1,25 (OH)2 vitamin D
Ca increased PO4 decreased Normal to increased PTH Increased Normal
What can be seen in the serum blood results in osteoporosis? Calcium Phosphate Alkaline phosphatase PTH 1,25 (OH)2 vitamin D
All normal
Where is alkaline phosphatase produced? (2)
Bone (osteoblasts)
Liver
Compare the matrix to mineral ratio in osteoporosis and osteomalacia.
Normal in osteoporosis but the whole box is smaller, but in osteomalacia there is more matrix so it is almost 50-50.
Both men and women lose bone mass from age of 40 onwards - at what rate?
0.7% a year
In women bone loss speeds up after menopause from 0.7% a year to…?
2-9% a year
Why are women more prone to osteoporosis?
Men start with more bone to begin with
Menopause speeds bone loss up
How is bone mineral density expressed?
T or Z score
What is the T-score?
Number of standard deviations from the young (30 yr) same sex and ethnicity mean
What is the Z-score?
Number of standard deviations from aged, sex and ethnicity matched mean
At what age do we have peak bone mass?
About 40
What does a T-score of greater than -1 mean?
Normal
What does a T-score of less than or equal to -2.5 mean?
Osteoporosis
What does a T-score of less than -1 and greater than -2.5 mean?
Osteopenia
What bones are more susceptible to osteoporotic bone loss? Give two examples.
Bones that have high proportion of trabecular bone
Vertebral bodies and femoral neck
What is the prevalence of osteoporosis at 50 years?
2%
What is the prevalence of osteoporosis at 80 years?
Greater than 25%
How is osteoporosis diagnosed? (2)
A fracture from low force (this is a red flag) DEXA scan (dual energy X-ray absorptiometry)
Why is trabecular bone particularly at risk? (2)
Greater surface area (10x more)
In locations that has to respond to new stresses
Fundamentally, what is osteoporosis?
Relative increase in resorption not matched by formation. The bone is normally mineralised, but there is simply less bone.
Describe the cortices and trabeculae in osteoporosis in osteoporosis. What about the osteoid?
Cortices and trabeculae thinned
Osteoid seems normal (approx 20% un-mineralised osteoid)
What is the lifetime risk of vertebral fracture in women over 50?
1:3
What is the lifetime risk of a neck of femur fracture in women over 50?
1 in 5
How many post-menopausal women are there in England and Wales?
2 million
How many fractures a year in post-menopausal women?
Name the three most common places.
180,000
Hip, wrist, then vertebral
In the osteoporosis treatment path, what is the non-pharmacological treatment? (3)
1500mg calcium supplements a day
800 IU vitamin D a day
Physical activity 3x a week for at least 30 mins
What else can be given for osteopororis? (6)
Alendronate Resedronate Raloxifene Calcitonin Etidronate HRT
What is excluded if there are vasomotor symptoms (and no fragility fractures)?
Etidronate
Who is HRT given to? How long for?
Oestrogen replacement 1st choice in peri-menopausal women. Treatment for at least 5 years.
What is raloxifene?
Selective oestrogen receptor modulator
What is denosumab? How is it given? How does it work?
Monoclonal antibody (binds to RANKL)
Subcutaneous injection every 6 months
Inhibits osteoclasts formation, activity and survival by binding to the RANKL
What is teriparatide? Why does this help with osteoporosis treatment?
Recombinant form of PTH
Intermittent exposure to PTH will activate osteoblasts more than osteoclasts (but chronically it will cause osteoclast proliferation).
What are bisphosphonates?
How many % do they reduce fracture risk by?
Potent inhibitors of bone resorption
Approx 50%
How do bisphosphonates work?
They are released locally during bone resorption and so are concentrated under the osteoclasts. They inhibit osteoclast activity and promote osteoclast apoptosis. They also may modulate signalling from osteoblasts to osteoclasts, causing increased OPG production and decreased RANKL expression.
What are the complications of bisphosphonates? (3)
Giant osteoclasts
Osteonecrosis of the jaw
Atypical fractures
Give two examples of atypical fractures.
Why does this occur with bisphosphonate treatment?
Subtrochanteric and femoral shaft
Old osteocytes signal for remodelling but fewer good osteoclasts.
What is the current osteoporosis treatment paradigm?
- Inhibitors of bone resorption (to slow the loss of bone mass, 3-6 years)
- Bone anabolic substances (to increased bone mass, but can’t recover lost microarchitecture, up to 2 years)
What is the future osteoporosis treatment paradigm?
- Bone anabolic substances (1 year)
2. Inhibitors of bone resorption (up to 6 years or even longer)
What is osteomalacia also known as?
Rickets
What is osteomalacia usually the result of?
Vitamin D deficiency either in diet or production
Is rickets more deforming in children or adults? Why?
Children
The epiphyseal growth plate is still open
What happens as a consequence of rickets?
Insufficient calcium and phosphate to mineralise new bone osteoid. Bones become softer and more liable to bend or fracture.
What are the lab results like for osteomalacia?
Calcium, Phosphorus and Alkaline phosphatase
Low serum calcium and phosphorus
High alkaline phosphatase
What type of fracture is common in osteomalacia? What can this progress to?
Pseudofractures (areas of unmineralised bone)
Can progress to insufficiency fractures
Where do pseudofractures form?
Areas of higher bone turnover
How many % is normal bone unmineralised osteoid?
How does this differ in osteomalacia?
<20%
There are wide seams of unmineralised osteoid. In severe cases up to 100% of bone covered by unmineralised osteoid.
With tetracycline labelling, what can be seen in rickets? (3)
Diffuse label (suggestive of altered mineralisation)
Single label
No label
Osteoid thickness must be greater than…?
14μm
What is the treatment for osteomalacia? (3)
Vitamin D supplements – may need to take for rest of life
Increase dietary calcium (milk, bread, beans, pulses, dried fruit, green leafy veg)
Sun/UV exposure (15 mins on hands and face 2-3x a week)
The liver converts cholecalciferol to…?
25-dihydroxyvitamin D3
The kidney converts 25-dihydroxyvitamin D3 to…?
1,25-dihydroxyvitamin D3
What is Paget’s disease also known as?
Osteitis deformans
What is the prevalence of Paget’s in population <40?
>50?
>80?
Rare
3%
10%
What are the 3 phases of Paget’s disease?
Initial phase
Compensatory/proliferative phase (mixed)
Burnt out/sclerotic phase
What is seen in the initial phase? (2)
Increased rate of bone resorption
Large number of giant osteoclasts
What is seen in the compensatory phase? (2)
Increased bone formation
Accelerated deposition in disorganised manner
What is seen in the burnt out phase? (5)
Bone hyper-cellularity may diminish leaving dense, “Pagetic bone”
Hyper-vascular bone marrow
Irregular thickened trabeculae
Prominent cement lines
Bone marrow replaced by fibrovascular connective tissue
What bones are commonly affected in Paget’s? (5)
pelvis femur vertebrae skull tibia
What is a rare complication of Paget’s disease?
Osteosarcoma
Where do osteosarcomas usually occur?
In long bones, often near the knee
Osteosarcoma is among the most malignant of cancers and it can spread rapidly, usually to lungs. To prevent spread, what can be done?
Removal of part of the affected bone, or limb amputation.
How is Paget’s treated? (5)
Bisphosphonates (work directly on osteoclasts to slow bone resorption) - oral 2-6 months, single to 3 IV infusion(s)
Calcium and vitamin D supplements
Pain management
Surgery
Calcitonin (used less than bisphosphonates)
Sclerostosis is also known as…?
How is it inherited?
Van Buchem syndrome
Autosomal recessive
What is Van Buchem syndrome associated with?
Associated with absence or reduced production of sclerostin
What cells secrete sclerostin? What does it do?
Osteocytes
Inhibits osteoblasts so stops bone formation
What happens in Van Buchem syndrome? (3)
Endosteal hyperostosis
Resistance to fracture
Excessive height
What is romosozumab?
By how much does it increase bone mass density and how does this compare to aldrenronate and teriparatide?
Sclerostin antibody
11.3% (compared to 4% and 7%)
