bone

Question 1

What is bone composed of? Describe each layer

Answer 1

• Cortical bone (hard, outer layer)
• Trabecular bone (spongy, inner layer)
• Cells (bone forming/resorbing cells)
• Extracellular (organic matrix- collagen, inorganic compounds)

Question 2

Describe osteoblasts

Answer 2

• Terminally differentiated
• Products of mesenchymal stem cells
• Make osteoid, hormones, matrix proteins, alkaline phosphotase
• Prerequisite for mineralisation

Question 3

Describe osteoclasts

Answer 3

• Large
• Multi nucleated
• Ruffled resorption border
• Break down bone
• Found in bone pits (resorption bays)
• Produce enzymes- tartrate resistant acid phosphatase & cathepsin K= breakdown ECM
• Help enhance blood Ca levels
• Regulated by hormones (PTH, Calcitonin, IL-6)
• Help with osteoclastic maturation & activity

Question 4

Describe osteocytes

Answer 4

• Star shaped
• Trapped/buried osteoblasts
• Communicate via cytoplasmic extensions
• Mechanosensory
• Involved in regulating bone matrix turnover

Question 5

How is normal bone formed?

Answer 5

• Resorption by osteoclasts

- Formation by osteoblasts

Question 6

What are the stages in bone formation?

Answer 6

• Resting
• Resorption
• Osteoid formation
• Mineralisation

Question 7

Give some examples of biochemical markers of bone turnover

Answer 7

• Formation: Alkaline phosphatase, procollagen type 1 propeptides
• Resorption: Crosslinked telopeptides of type 1 collagen
• Osteoclast enzymes: tartrate resistant acid phosphatase, cathepsin K

Question 8

What is bone alkaline phosphatase?

Answer 8

• Released by osteoblasts
• Involved in mineralisation
• Release stimulated by increased bone remodelling

Question 9

Describe P1NP

Answer 9

• Synthesised by osteoblasts
• Precursor molecule of type 1 collagen
• Increases with increased osteoblast activity
• Decreased by reduced osteoblast activity

Question 10

Why are bone markers used?

Answer 10

• Evaluation of bone turnover & bone loss
• Evaluation of treatment effect
• Compliance with mediation

Question 11

How is bone mass investigated?

Answer 11

DEXA

Question 12

What are T scores and what do certain values mean?

Answer 12

• Bone density
• -1+ normal bone density
• -2.5- -1 osteopenia
• -4- -2.5 osteoporosis

Question 13

Name some bone disorders

Answer 13

• Metastic disease
• Paget’s disease
• Osteoporosis
• Osteomalacia/rickets
• Hyperparathyroidism

Question 14

Describe osteoporosis

Answer 14

• Dec bone mass & deranged bone micro architecture= failure of structural integrity
• Loss of bone
• Propensity to fractures- spine & hip
• Diagnosis by DEXA/Xray

Question 15

What are common sites of fragility fractures?

Answer 15

• Spine
• Neck of femur
• Wrist

Question 16

What are secondary causes of osteoporosis?

Answer 16

• Endocrine: Early menopause, diabetes, Cushings,
• GI: Coeliac, IBD, chronic liver disease
• Haematological: myeloma, haemoglobinopathies
• Respiratory: COPD, CF
• Drugs: steroids, heparin, anti-convulsants, ciclosporin
• Rheumatological: RA
• Metabolic: homocysturia

Question 17

What investigations can be carried out for secondary causes of osteoporosis?

Answer 17

• Ca & bone profile
• TFTs
• FBC (U&Es- estimated GFR)
• Vit D
• PTH
• Coeliac screen
• Plasma viscosity

Question 18

What are the types of treatments for osteoporosis?

Answer 18

• Anabolic

- Antiresorptives: bisphosphonates

Question 19

What is the mechanism of action for bisphosphonates?

Answer 19

• Mimic pyrophosphate structure
• Taken up by skeleton
• Concentrated in newly mineralising bone under osteoclasts
• Local release during bone resorption
• Modulate signalling from osteoblasts to osteoclasts
• Ingested by osteoclasts
• Inhibit osteoclast formation, migration, activity, promote apoptosis

Question 20

What are problems with using bisphosphonates?

Answer 20

• Poor absorption
• Cause oesophageal/ upper GI problems
• Flu-like side effects
• Osteonecrosis of jaw
• Atypical femur fractures

Question 21

What types of bone metastases are there?

Answer 21

• Lytic: breast, lung, destruction of normal bone (osteoclasts)
• Sclerotic/osteoblastic: deposition of new bone, prostate, lymphoma

Question 22

What is the clinical presentation of bone metastasis?

Answer 22

• Pain: worse at night, better with movement, constant
• Broken bones: femur, humerus, vertebral, pathological
• Numbness/paralysis/trouble urinating: spinal cord compression
• Loss of appetite/nausea/thirst/fatigue/confusion: symptoms of hypercalcaemia
• Anaemia: disruption of bone marrow

Question 23

What are the symptom of hypercalcaemia?

Answer 23

• Severe: abdo pain, vomiting, coma, pancreatitis, dehydration, arrhythmias
• Mild: nausea, fatigue, constipation, anorexia, mood changes, polyuria/dipsia

Question 24

Which cells secrete PTH?

Answer 24

Chief cells of parathyroid gland

Question 25

What are the roles of PTH?

Answer 25

- Inc decomposition of bone releasing Ca - Inc absorption of Ca from food by intestines - Inc reabsorption of Ca from urine by kidneys - All lead to inc levels of blood Ca

Question 26

What are the causes and signs of primary hyperparathyroidism?

Answer 26

- Sporadic or familial - Ca high - PTH high - Low phosphate - High alkaline phosphatase - Adenomas: encapsulated & consist of chief cells - Parathyroid carcinoma: aggressive, severe hypercalcaemia - Glandular hyperplasia: all 4 glands enlarged, sporadic or genetic MEN1, MEN2A - Ectopic adenomas: in mediastinum/thymus gland, migrate during embryogenesis

Question 27

What are the causes and signs of secondary hyperparathyroidism?

Answer 27

- CKD, vit D deficiency - Normal/low Ca - PTH high - High phosphate if due to kidney problems

Question 28

What are the causes and signs of tertiary hyperparathyroidism?

Answer 28

- prolonged secondary hyperparathyroidism, CKD - High Ca - High PTH - High or low phosphate

Question 29

What are the classical symptoms of primary hyperparathyroidism?

Answer 29

- Hypercalcaemic symptoms - Renal disease/ CKD/ nephrolithiasis - Bone disease/ osteoporosis/osteitis/fibrosa cystica - Proximal muscle wasting

Question 30

What are Calcimimetics used for and how do they work?

Answer 30

- Normalise Ca in sympotmatic patients/not fit for surgery | - Activates CaSR in PT gland leading to reduced PTH secretion

Question 31

Describe Paget's disease of the bone

Answer 31

- Rapid bone turnover & formation - Abnormal bone remodelling - 50+ - Polyostotic or monostotic - Elevated alkaline phosphatase reflecting inc bone turnover

Question 32

What are clinical features of Page's disease?

Answer 32

- Bone pain - Bone deformity - Fractures - Arthritis - Cranial nerve defects if skull affected (hearing/vision loss) - Risk of osteosarcoma

Question 33

Which bones are most commonly affected by Paget's disease?

Answer 33

- Pelvis - Femur - Lower lumbar vertebrae

Question 34

What is osteomalacia?

Answer 34

- Lack of mineralisation of bone due to it D deficiency/lack of Ca/phosphate - Widened osteoid seams - Childhood rickets: widened epiphyses & poor skeletal growth

Question 35

What are the main causes of osteomalacia?

Answer 35

- Insufficient Ca absorption from intestines (diet or resistance) - Excessive renal phosphate excretion (genetic)

Question 36

What are clinical features of osteomalacia?

Answer 36

- Muscle & bone weakness - Diffuse bone pains (symmetrical) - High alkaline phosphatase & PTH - Low vit D & Ca - Secondary hyperparathyroidism