Metabolic Bone Disease – Histopathology Flashcards

1
Q

What are the three main functions of bones?

A

Mechanical – support and site for muscle attachment
Protective
Metabolic – reserve of calcium

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2
Q

What are the two main components of bone and what are their relative proportions?

A

Inorganic (65%) – calcium hydroxyapatite (store of 99% of the body’s calcium, 85% of the phosphorous and 65% of Na and Mg)
Organic (35%) – bone cells and protein matrix

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3
Q

Describe the classification of bone as cortical and cancellous.

A
Cortical  
 Long bones 
 80% of skeleton 
 Appendicular skeleton 
80-90% calcified 
 Mainly mechanical and protective role 
Cancellous 
 Vertebrae and pelvis  
 20% of skeleton  
 Axial  
15-25% calcified  
 Mainly metabolic 
 Large surface
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4
Q

What are the indications for bone biopsy?

A
Evaluate bone pain or tenderness 
Investigate abnormality seen on X-ray  
For bone tumour diagnosis  
To determine the cause of unexplained infection  
To evaluate therapy
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5
Q

What are the two types of bone biopsy?

A

Closed – needle – core biopsy with Jamshidi needle

Open – for sclerotic or inaccessible lesions

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6
Q

What are the three types of bone cell?

A

Osteoblast – build bone by laying down osteoid
Osteoclast – multinucleate cells of the macrophage family that resorb bone
Osteocyte – osteoblast like cells

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7
Q

Where are osteocytes found?

A

Lacunae

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8
Q

What cytokine is important for stimulating the differentiation of osteoclast precursors into pre-osteoclasts?

A

M-CSF (this is produced by osteoblasts)

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9
Q

Which cells produce RANKL and what is its effect?

A

Pre-osteoblasts

It stimulates the maturation of osteoclasts

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10
Q

What do mature osteoblasts produce that blocks the RANK/RANKL binding?

A

Osteoprotegrin

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11
Q

How are bones classified anatomically?

A

Flat
Long
Cuboid

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12
Q

What type of ossification leads to the formation of:

a. Long Bones
b. Flat Bones

A

a. Long bones
Endochondral ossification
b. Flat bones
Intramembranous ossification

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13
Q

How else can bone be classified?

A

Trabecular (cancellous) or compact (cortical)

Woven (immature) or lamellar (mature)

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14
Q

What is metabolic bone disease?

A

Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc.)
Overall effect is reduced bone mass (osteopaenia) often resulting in fractures from little or no trauma

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15
Q

What are the three main categories of metabolic bone disease?

A

Related to endocrine abnormality (e.g. Vit D and PTH)
Non-endocrine (e.g. age-related osteoporosis)
Disuse osteopaenia

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16
Q

Describe the staining of calcified and uncalcified bone.

A

Calcified – green

Uncalcified – orange

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17
Q

What are the primary causes of osteoporosis?

A

Age

Post-menopause

18
Q

What are the secondary causes of osteoporosis?

A

Drugs

Systemic disease

19
Q

Describe the histology of osteoporotic bone.

A

Weak trabecular bridging

Holes and cysts

20
Q

What is osteomalacia and what can it be caused by?

A
Condition of defective bone mineralisation that can be caused by: 
Vitamin D deficiency  
Phosphate deficiency (usually related to chronic renal disease)
21
Q

What are the metabolic and endocrine consequences of vitamin D deficiency?

A

Secondary hyperparathyroidism –> increased bone resorption

Hypocalcaemia – neuronal excitability causing muscle twitching, spasms, tingling and numbness

22
Q

Describe the histology of osteomalacia.

A

No calcification of bone
More uncalcified osteoid
Bones are very bendy and cannot carry musculature very easily

23
Q

What are the clinical consequences of osteomalacia?

A

Bone pain/tenderness
Fracture (horizontal fractures at Looser’s zone at the neck of the femur are commonly seen)
Proximal weakness
Bone deformity

24
Q

What is used to investigate mineralisation?

A

Fluorescent tetracycline labelling

25
Q

What are the consequences of hyperparathyroidism?

A

Hypercalcaemia (increased Ca2+ reabsorption)
Hypophosphataemia (increased phosphate excretion in the urine)
Osteitis fibrosa cystica (due to increased osteoclast activity)

26
Q

List the four organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.

A

Parathyroid glands
Bones
Kidneys
Proximal small intestine

27
Q

State some causes of primary hyperparathyroidism.

A

Parathyroid adenoma

Chief cell hyperplasia

28
Q

State some causes of secondary hyperparathyroidism.

A

Chronic renal insufficiency

Vitamin D deficiency

29
Q

What are the symptoms of hyperparathyroidism?

A
Stones, Bones, Abdominal Groans and Psychic Moans 
Stones – calcium oxalate renal stones  
Bones – osteitis fibrosa cystica  
Abdominal Groans – acute pancreatitis  
Psychic Moans – psychosis and depression
30
Q

What is the most important investigation for hyperparathyroidism and what will it show in someone with hyperparathyroidism?

A

X-ray of the hand
Subperiosteal bone erosions
Brown cell tumours – small areas of resorption in the long bones of the fingers that are filled with osteoclasts

31
Q

What are the five features of renal osteodystrophy?

A
Increased bone resorption (osteitis fibrosa cystica)  
Osteomalacia  
Osteoporosis 
Osteosclerosis  
Growth retardation
32
Q

What are the consequences of renal osteodystrophy?

A
Hyperphosphataemia 
Hypocalcaemia as a result of a decrease in vitamin D metabolism 
Secondary hyperparathyroidism 
Metabolic acidosis  
Aluminium deposition
33
Q

What is Paget’s disease?

A

Disorder of bone turnover (there is a lack of proper communication between the cells)

34
Q

What are the three stages of Paget’s disease?

A

Osteolytic
Osteolytic-osteosclerotic
Quiescent osteosclerotic

35
Q

Describe the histology of Paget’s disease.

A

Prominent reversal lines

Masses of osteoclasts in the same site as osteoblasts

36
Q

In which ethnicities is Paget’s disease rare?

A

Asian

African

37
Q

Which sites does Paget’s disease most commonly affect?

A
Skull 
Sternum 
Spine 
Humerus 
Pelvis 
Femur  
Tibia
38
Q

List some clinical features of Paget’s disease.

A
Pain 
Microfractures  
Nerve compression  
Skull changes  
Deafness  
Haemodynamic changes  
Cardiac failure  
Hypercalcaemias 
Development of sarcoma in the area of involvement
39
Q

What is a Haversian canal?

A

Channel that blood vessels run in within bone

40
Q

What are Howship’s Lacunae?

A

Pits in the bone surface where osteoclasts are found (also called resorption bays)