Theme 5: Bone and New Markers Flashcards
1
Q
What is the purpose of bone?
A
- structural support
- protects vital organs
- bank for calcium, phosphate etc
- home for bone marrow
2
Q
What is cortical bone?
A
- the hard outer layer
- a.ka compact bone
- gives bone its smooth, white and solid appearance
- accounts for 80% of total bone mass in adult skeleton
3
Q
What is an osteon?
A
individual microscopic columns that together all make up cortical bone
functional unit of cortical bone
4
Q
What is one osteon made up of?
A
multiple layers of osetoblasts and osteocytes around a central canal called the haversian canal
5
Q
What connects individual osteons together?
A
Volkmann’s canals
6
Q
What is the outer surface of cortical bone covered by?
A
periosteum
7
Q
What is the inner surface of cortical bone covered by?
A
endosteum
8
Q
What is the endosteum?
A
the boundary between the cortical bone and the inner trabecular bone
9
Q
What is trabecular bone?
A
- spongy inner layer
- open cell porous network
- thin formations of osteoblasts covered in endosteum create an irregular network of spaces
- bone marrow and RBCs within these spaces
10
Q
Where is bone marrow found?
A
trabecular bone
11
Q
Which are the bone forming cells?
A
osteoblasts –> they create and repair new bone
12
Q
Which are bone resorbing cells?
A
osteoclasts
13
Q
Which are bone co ordinating cells?
A
osteocytes (which are trapped/buried osteoblasts)
14
Q
what is the organic matrix of bone made up of?
A
mainly collagen (osteoid) and ground substance
15
Q
What is the inorganic component of bone made up of?
A
hydroxyapatite (calcium and phosphate) and minerals (magnesium, sodium and potassium)
16
Q
What are the 5 functions of osteoblasts?
A
- Make osteoid
- Mineralise organic matrix
- Communicates with other bone cells
- Makes hormones
- Become osteocytes
17
Q
What do osteoclasts do?
A
- breakdown old bone
- produce enzymes such as TRAP to breakdown extracellular matrix
- Help enhance blood calcium levels
18
Q
Which hormones regulate osteoclasts?
A
PTH, calcitonin and IL-6
19
Q
What do osteocytes do?
A
- Give bone mechanosensory properties e.g how the bones know its being used
- Co-ordinate regulation of bone turnover - osteocytes tell the bones what to do and when to do it
20
Q
Explain the bone cycle/ remodelling
A
- normal bone is in constant state of turnover caused by resorption by osteoclasts and formation of osteoblasts
- Osteoclasts reabsorb and break down bone
- signals to osteoblasts
- The nutrients are reabsorbed, and osteoblasts lay down new osteoid
21
Q
What is the relationship between bone mass and age?
A
- bone mass increases with age until peak at 30 in females and 45 in males
- then bone mass decreases with age
- with increasing age, osteoblastic activity falls and osteoclastic activity increases
22
Q
Why do women loose bone mass more rapidly than men?
A
oestrogen helps maintain bone health so there is faster bone loss due to menopause
23
Q
Which biochemical markers can we measure when looking at bone formation (i.e production of active osteoblasts) ?
A
- alkaline phosphatase
- osteocalcin
- P1NP (procollagen type 1N propeptides)
24
Q
Which biochemical markers can we measure when looking at bone resorption (i.e what is released when bone is broken down) ?
A
- hydroxyproline
- pyridinium crosslinks
- cross linked telopeptides of type 1 collage (NTX, CTX)
25
Why is bone alkaline phosphatase useful to measure?
- released by osteoblasts
- release stimulated by increased bone remodelling/ when bone turnover changes
- can show fractures, hyperparathyroidism, pagets disease and pubertal growth spurts
26
What is P1NP and why do we measure it?
- precursor molecule of type 1 collagen
- synthesised by osteoblasts
- increased with osteoblast activity
- decreased by reduced osteoblast activity
27
Why do we measure collagen cross links? (NTX, CTX)
- Cross linking molecules which are released with bone resorption, correlate highly with bone resorption
- increased in periods of high bone turnover - hyperthyroidism, adolescents and menopause
28
What is DEXA imaging?
- measures bone mass (bone density X-ray)
| - measured in T-scores
29
What is a T-score?
number of standard deviations away from the mean compared to a young healthy person of the same sex on a DEXA scan
- 1 and above = normal bone density
- 1 and -2.5 = low bone mass --> osteopenia
- 2.5 and below --> osteoporosis
30
What is osteoporosis?
a systemic skeletal disease characterised by LOW bone mass and deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture
-decrease bone mass --> failure of structural integrity
31
What is a fragility fraction?
- fracture that occurs as a result of minimal trauma, such as falling from a standing height or less, or no identifiable trauma
- a fracture caused by injury that would be insufficient to fracture a healthy bone
32
What are the common sites for fracture?
- spine
- neck of femur
- wrist
33
What are the risk factors for fracture?
- age
- sex - F>M
- recent fragility fracture
- smoking
- alcohol
- falls
- drugs
- inflammatory conditions
- malabsorption
- T1 DM
- family history
- BMI
34
How can we predict the risk of a fracture for a patient with osteoporosis?
FRAX
35
What are the secondary causes of osteoporosis?
- early menopause
- hyperthyroidism
- cushings
- any cause of malabsorption
- RA
- COPD
- cystic fibrosis
- glucocorticoids
- immobility
- CKD
36
What are the different ways of investigating the secondary causes of osteoporosis?
- calcium and bone profile
- U&Es
- TFTs
- FBC
- VitD
- PTH
- coeliac screen
- FSH, LH, oestradiol, prolactin
37
What is antiresorptive treatment?
- for prevention of osteoporotic fractures
- stops bone breakdown by acting on osteoclasts
- commenest drugs are bisphosphonates
38
What is anabolic treatment?
works on osteoblasts in preventing osteoporotic fractures
39
What is the mechanism of action of bisphosphonates?
- inhibit osteoclast formation, migration and osteolytic activity, promote apoptosis
- modulate signalling from osteoclasts to osteoblasts
- concentrated in newly mineralising bone and under osteoclasts
40
What is denosumab?
- a RANK ligant inhibitor (as RANK ligand causes osteoclasts to mature and develop)
- highly effective injection
- inhibits osteoclast formation, function and survival
- increase in spine bone density
41
Where can osteolytic bone mets occur?
- breast/lung
- kidney/thyroid
- destroys normal bone (osteoclasts) --> can lead to hypercalcaemia
42
Where can sclerotic/osteoblastic bone mets occur?
- prostate
- lymphoma
- breat/lung
43
Where are the usual sites of spread of bone metastases?
```
spine
pelvis
femur
humerus
skull
```
44
What are the presenting features of bone mets?
* Pain – often worse at nights and initially gets better with movement, usually becomes constant
* Broken bones
* Numbness, paralysis, trouble urinating – spinal cord compression from bone metastases
* Loss of appetite, nausea, thirst, confusion, fatigue – symptoms of hypercalcaemia
* Anaemia – disruption of bone marrow
45
What are the symptoms of mild and severe hypercalcaemia
Mild:
- polyuria, polydypsia
- mood disturbance
- anorexia
- nausea, fatigue
- constipation
Severe:
- abdo pain
- vomiting
- coma
- pancreatitis
- dehydration
- cardiac arrhythmias
46
What is the next blood test you could do in anyone with a high calcium level?
parathyroid hormone - the predominant control for calcium levels
47
How does PTH control calcium levels?
• When blood calcium becomes low, the calcium sensing receptors on parathyroid gland detect this and release parathyroid hormone
• This leads to restoration of calcium levels
• Once calcium has gone back to normal we have negative feedback mechanisms to reduce PTH levels
-Mg and VitD also affect PTH
48
What are the non-PTH mediated causes of hypercalcaemia? (so PTH will be low)
- malignancy
- vitD intoxication
- medications
- immobilisation
- endocrine disorders - hyperthyroidism, acromegaly, phaeochromocytoma
49
What are the PTH mediated causes of hypercalcaemia? (so PTH will be high\)
primary hyperparathyroidism
50
What is primary hyperparathyroidism?
- parathyroid glands malfunction and make too much PTH and don't sense calcium properly so calcium raises as well
- also will have low phosphate and high alk phos
51
What is secondary hyperparathyroidism?
- parathyroid working fine
- low calcium is detected so we raise PTH
- this is not a problem
- causes are usually CKD or VitD deficiency
52
What is the association between adenomas and PHPT?
1. adenoma
- single adenoma accounts for 85% of cases of PHPT
2. Glandular hyperplasia
- all 4 glands enlarged
3. Ectopic adenomas
4. Parathyroid carcinoma
53
How would we treat patients with symptomatic hypercalcaemia?
surgery - removing parathyroid - is best option
54
Which drugs can we use to treat PHPT?
Calcimimetics:
- activate CaSR in the parathyroid gland
- therefore leads to reduced PTH secretion
55
What is Paget's disease of bone?
- rapid bone turnover and formation
- leading to abnormal bone remodelling
- mainly 50+ yo , M>F
- polyostotic (affecting many bones) or monostotic (affecting one bone)
- elevated alkaline phosphatase reflecting increased bone turnover
- FH in 10-15% of cases
56
What are the clinical features of Paget's disease?
- bone pain
- bone deformation
- fractures
- arthritis
- cranial nerve defects if skull affected - hearing and vision loss
- risk of osteosarcoma
- most commonly affects pelvis, femur and lower lumbar vertebrae
57
What investigations of Pagets can we perform?
lab assessment
plain x-RAYS
Nuclear medicine bone scan
58
What is the best treatment for Pagets?
bisphosphates - give bisphosphates to slow down bone turnover - same treatment as osteoporosis
59
What is osteomalacia?
- adult rickets
| - lack of mineralisation of bone - not enough calcium, phosphate
60
What is the difference between childhood rickets and osteomalacia in adults?
adult form - widened osteoid seams with lack of mineralisation
rickets - widened epiphyses and poor skeletal growth
61
What are the causes of osteomalacia?
1. Insufficient calcium absorption from intestine - due to lack of dietary calcium or vitD deficiency/resistance
2. Excessive renal phosphate excretion
62
What are the clinical features of osteomalacia?
- diffuse bone pain - usually symmetrical
- muscle weakness
- bone weakness
- high alk phos, low vitD, possibly low calcium and high PTH (secondary hyperparathyroidism)
- malabsorption
