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YR2: Musculoskeletal > Metabolic Bone Disease – Histopathology > Flashcards

Metabolic Bone Disease – Histopathology Flashcards

1
Q

What are the 4 main functions of bones?

A

Structure: give structure + shape to the body

Mechanical: site for muscle attachment

Protective: vital organs + bone marrow

Metabolic: reserve of calcium + other minerals

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2
Q

What are the 2 main components of bone and what are their relative proportions?

A

Inorganic (65%): calcium hydroxyapatite (store of 99% of the body’s Ca, 85% of phosphorous)

Organic (35%): bone cells + protein matrix

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3
Q

Describe the classification of bone as cortical

A

Long bones

80% of skeleton

Appendicular skeleton

80-90% calcified

Mainly structural, mechanical + protective role

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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 cause of unexplained infection

To evaluate therapy

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5
Q

What are the 2 types of bone biopsy?

A

Closed: (Jamshidi) needle inserted into biopsy site

Open: for sclerotic or inaccessible lesions

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6
Q

What are the 3 types of bone cell?

A

Osteoblasts: mononuclear cells, produce osteoid to form new bone

Osteoclasts: multinucleate cells, resorb bone

Osteocyte: mechanosensory network embedded in mature bone

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7
Q

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

A

M-CSF (produced by osteoblasts)

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8
Q

Which cells produce RANKL and what is its effect?

A

Pre-osteoblasts

It stimulates the maturation of osteoclasts

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9
Q

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

A

Osteoprotegrin (decoy receptor for RANKL)

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10
Q

How are bones classified anatomically?

A

Flat: Skull

Long: Femur

Short: Carpals

Irregular: Pelvis

Sesamoid: Patella

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11
Q

What type of ossification leads to the formation of: a. Long Bones b. Flat Bones

A

Long bones = Endochondral ossification

Flat bones = Intramembranous ossification

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12
Q

How else can bone be classified?

A

Macroscopically: Trabecular (cancellous/spongey) or compact (cortical)

Microscopically: Woven (immature) or lamellar (mature)

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13
Q

What is metabolic bone disease?

A

Reduced bone mass + strength due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc.)

Causes altered bone cell activity, rate of mineralisation or changes in bone structure

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14
Q

What are the 3 main categories of metabolic bone disease?

A

Related to endocrine abnormality (e.g. Vit D + PTH)

Non-endocrine (e.g. age-related osteoporosis)

Disuse osteopaenia

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15
Q

Describe the staining of mineralised and unmineralised bone

A

Mineralised: green

Unmineralised: orange

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16
Q

What are the primary and secondary causes of osteoporosis?

A

Primary: Age, Post-menopause

Secondary: Drugs, Systemic disease

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17
Q

What is osteoporosis?

A

BMD T-score of -2.5 or lower SDs different from mean peak BMD

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18
Q

Describe the histology of osteoporotic bone.

A

Thinner, less interconnected trabeculae

Some trabeculae are free floating

Holes + cysts

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19
Q

What is osteomalacia and what can it be caused by?

A

Defective bone mineralisation of normally synthesised bone matrix

Can be caused by:

Vitamin D deficiency

Phosphate deficiency (usually related to CKD)

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20
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 + numbness

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21
Q

Describe the histology of osteomalacia.

A

No mineralisation of bone

More unmineralised osteoid

Bones are very bendy + cannot carry musculature easily

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22
Q

What are the clinical consequences of osteomalacia?

A

Bone pain/tenderness

Fracture (horizontal fractures at Looser’s zone at neck of femur are common)

Proximal weakness

Bone deformity

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23
Q

What is used to investigate mineralisation?

A

Masson-Goldner Trichrome staining

24
Q

What are the consequences of hyperparathyroidism?

A

Increased Ca2+ + PO4 excretion in urine

Hypercalcaemia (increased Ca2+ reabsorption)

Hypophosphataemia (increased phosphate excretion in urine)

Osteitis fibrosa cystica (due to increased osteoclast activity)

25
Q

List the 4 organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.

A

Parathyroid glands

Bones

Kidneys

Proximal small intestine

26
Q

State 2 causes of primary hyperparathyroidism.

A

Parathyroid adenoma

Chief cell hyperplasia

27
Q

State 2 causes of secondary hyperparathyroidism.

A

Chronic renal deficiency

Vitamin D deficiency

28
Q

List 4 symptoms of hyperparathyroidism?

A

Stones: calcium oxalate renal stones

Bones: osteitis fibrosa cystica

Abdominal Groans: acute pancreatitis

Psychic Moans: psychosis + depression

29
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

30
Q

What are the 5 features of renal osteodystrophy?

A

Increased bone resorption (osteitis fibrosa cystica)

Osteomalacia

Osteoporosis

Osteosclerosis

Growth retardation

31
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

32
Q

What is Paget’s disease?

A

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

33
Q

What are the 3 stages of Paget’s disease?

A

Osteolytic (focal bone loss)

Osteolytic-osteosclerotic (osteoblasts respond to increased resorption)

Quiescent osteosclerotic (results in disorganised lamellae in mosaic pattern)

34
Q

Describe the histology of Paget’s disease.

A

Prominent reversal lines

Masses of osteoclasts in the same site as osteoblasts

Coarse, disorganised trabeculae

Thickened cortices

35
Q

Describe epidemiology of Paget’s disease

A

Onset >40

M > F

Rare in Asian/ African

Majority polyostic

36
Q

Which sites does Paget’s disease most commonly affect?

A

Skull

Sternum

Spine

Humerus

Pelvis

Femur

Tibia

37
Q

List 9 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

38
Q

What is a Haversian canal?

A

Channel that blood vessels run in within bone

39
Q

What are Howship’s Lacunae?

A

Pits in the bone surface where osteoclasts are found (AKA. resorption bays)

40
Q

Describe the classification of bone as cancellous.

A

Vertebrae + pelvis

20% of skeleton

Axial

15-25% calcified

Mainly metabolic

Large SA

41
Q

What is the function of the osteocyte canalicular network formed by dendritic process between osteocytes?

A

Mechanosensory function

Allows bone to signal location that requires repairing or removing

42
Q

Describe the micro anatomy of cortical bone

A

Organised in parallel columns composed of lamellae (concentric rings of bone surrounding a central channel).

Lamellae form when osteocytes lay bone matrix + entrap themselves in lacunae spaces

43
Q

What is the circumferential lamellae surrounding the whole bone shaft?

A

Periosteum

44
Q

Describe the micro anatomy of cancellous bone

A

Anastomosing strips of slender bone (trabeculae) enclose marrow + blood vessels.

45
Q

Where would you find immature bone?

A

Developing skeleton

Sites of rapid growth

Sites of pathological bone turnover

46
Q

Describe the bone remodelling cycle

A

Osteocytes apoptose, releasing RANKL which signals for osteoclasts to form at that site

Osteoclasts resorb old/ damaged bone

Osteoclasts die away

Osteoblasts produce osteoid to replace the bone that’s been removed

47
Q

How could you differentiate between the bone cells histologically?

A

Osteoblasts= mononuclear, cuboidal, flat, on surface

Osteoclasts= multinucleate

Osteocytes= embedded in lacunae

48
Q

What is used to investigate dynamic rate of bone turnover? How?

A

Tetracycline/ Calcein labelling

Inject on 2 separate occasions, measure distance between 2 lines formed

49
Q

What are the 3 different types of osteoporosis?

A

High turnover: increased resorption (more so than formation)

Low turnover: decreased formation (more decreased than resorption)

Increased resorption + decreased formation

50
Q

Label the diagram

A

Cortical bone

51
Q

Label the diagram

A

Cartilage

52
Q

Label the diagram

A

Cancellous bone

53
Q

Label the diagram

A

Epiphyseal line

54
Q

Label the diagram

A

Medullary cavity

55
Q

Label the diagram

A

Marrow

YR2: Musculoskeletal (10 decks)

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