Bone and new markers Flashcards
1
Q
Composition of bone
A
- Cortical bone - hard outer layer makes up 80%
- Trabecular/cancellous bone = Spongy inner layer 20%
- Extracellular = organic matrix (collagen) + Inorganic components (calcium eg)
2
Q
Osteoblasts
A
- Create and repair new bone
- Make osteoid - consisting of type 1 collagen
- Make hormone - osteocalcin
3
Q
Osteoclasts
A
- Breakdown old bone
- Releases calcium into the bloodstream
- Found in bone pits
- Produce enzymes such as TRAP and cathepsin K to dissolve bone
- Responsive to hormones eg IL-6
4
Q
Osteocytes
A
- Buried osteoblasts
- Communicate via cytoplasmic extensions
- Mechanosensory properties
- Co-ordinate regulation of bone turnover - osteocytes signal osteoclast where bone needs to be broke
5
Q
Is Bone a a dynamic tissue?
A
Yes - Constant remodelling, highly vascular tissue, metabolically active.
6
Q
Bone cycle
A
- Resting bones with lining cells
- Osteocytes signal that bone needs to be broke
- Osteoclasts reabsorb area of bone and signal osteoblasts
- Osteoblasts from osteoid to form hard bone
7
Q
What affects the bone cycle
A
- Loss of oestrogen = more loss of bone mass
- With increasing age, the rate of bone resorption exceeds the rate
of bone formation, hence there is a gradual decrease in bone mass
8
Q
What is DEXA scanning
A
- Bone mass (calcium) investigation - shine a little bit of radiation through bone for densitometry result.
9
Q
Alkaline phosphate
A
- Biochemical marker of bone formation
- Elevated ALP from liver or bone problems
- Bone specific ALP = involved in mineralisation, released by osteoblasts
- Release stimulated by increased bone remodelling - due to puberty, hyperparathyroidism, Paget’s
10
Q
P1NP - procollagen type 1N propeptides
A
- Biochemical marker of bone formation
- Synthesised by osteoblasts – pecursor molecule of type 1 collagen
- Increased with increased osteoblast activity, decreased by reduced osteoblast activity
11
Q
Collagen cross-links (NTX, CTX)
A
- Biochemical marker for bone resorption
- Cross-linking molecules released in bone resorption
- Increased in periods of high bone turnover
- sensitive to nutrition so needs to be done fasted in the morning
12
Q
Osteoporosis
A
- low bone mass and microarchitectural deterioration of bone tissue, increase in bone fragility and susceptibility to fracture.
- diagnosis relies of DEXA/X-ray (less than -2.5)
- Increased Kyphosis - changed centre of balance
13
Q
What is a fragility fracture
A
- A fracture that should not occur = suggestive of low bone mass
- Common sites - Lumbar spine, wrist, neck of femur
- FRAX calculation tool
14
Q
Secondary causes of osteoporosis
A
- Diabetes
- Cushing’s
- Prostate cancer
- Hormone ablation from breast
- Hyperparathyroidism
15
Q
Treatment of osteoporosis
A
- Antiresorptive treatments = work on osteoclasts (Raloxifene, denosumab)
- Anabolic treatment on osteoblasts
- First line is bisphosphonates - taken up by skeleton , ingested by osteoclasts and bisphosphonate kills osteoclast so potently antiresorptive.
16
Q
Bone metastases
A
2 types:
- Lytic = breast/lung, kidney/ thyroid
- Sclerotic/osteoblastic = deposition of new bone
17
Q
Presenting symptoms of bone metastases
A
- Bone pain, broken bone
- Numbness due to spinal cord compression
- Hypercalcaemia (especially lytic)
18
Q
Hypercalcaemia symptoms
A
- Mild = polyuria, anorexia, nausea, constipation
- Severe = abdominal pain, vomiting, pancreatitis, cardiac arrhythmias, kidney stone
19
Q
Causes of hypercalcaemia
A
- check PTH hormone (would expect it to be suppressed)
- Malignancy – PTH low – 95% of hypercalcaemia case
- Vitamin D intoxication
- Sporadic primary hyperparathyroidism – PTH high – no negative feedback
20
Q
Parathyroid hormone
A
- PTH secreted by chief cells
- Low calcium detected by calcium sensing receptor which tells parathyroid gland to make X amount of PTH which then acts on bone, bowel and kidneys to restore blood calcium – negative feedback
21
Q
Primary hyperparathyroidism
A
- Inappropriately elevated PTH in the presence of high calcium suggests PHPT
- Symptoms of hypercalcaemia
22
Q
Causes of PHPT
A
- Benign – single adenoma accounts for 85% of PHPT
- Glandular hyperplasia – all 4 glands enlarged; 6-10%
- Ectopic adenoma
- Parathyroid carcinoma
23
Q
Treatment of PHPT
A
- Surgery for symptomatic hypercalcaemia
- Calcimimetics - Cinacalcet suppresses calcium by reducing PTH secretions
24
Q
Paget’s disease
A
- Cotton wool appearance in trabecular bone – thickened deformed cortical bone
- increased bone breakdown (lytic areas)
- Abnormal bone remodelling
- Elevated ALP reflecting increased bone turnover
25
Q
Clinical features of Paget’s disease
A
- Bone pain
- Bone deformity
- Fractures
- Most commonly affects pelvis, femur and lower lumbar vertebrae
26
Q
Management of Paget’s
A
- Investigations – X-rays (appearance), nuclear medicine bone scan (activity and extent of disease)
- Treatment – bisphosphonates – reduce osteoclast function; monitor disease using TAP, BAP or P1NP
27
Q
Osteomalacia
A
- Lack of mineralisation in bone
- Adult form – widened osteoid seams with lack of mineralisation
- Classic childhood rickets – widened epiphyses and poor skeletal growth
28
Q
Causes of Osteomalacia
A
- Insufficient calcium absorption from intestines - due to lack of dietary calcium or vitamin D deficiency/ resistance
- Excessive renal phosphate excretion – rare genetic forms e.g. hereditary hypophosphataemic rickets
29
Q
Clinical features of Osteomalacia
A
- possibly low calcium and high PTH (secondary hyperparathyroidism)
- Diffuse bone pains – symmetrical, muscle weakness, bone weakness
- High ALP, low Vit D
