Metabolic bone disease histopathology Flashcards

1
Q

Functions of bone

A
STRUCTURE
structure and shape to body
MECHANICAL
site for muscle attachment
PROTECTIVE
vital organs and bone marrow
METABOLIC
reserve of calcium
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2
Q

State the composition of bone

Outline what is contained in the metaphysis

A

Composition:

INORGANIC - 65%

  • calcium hydroxyapatite (10Ca 6PO4 OH2)
  • is storehouse for 99% of Ca in the body
  • 85% of the phosphorous, 65% Na & Mg

ORGANIC - 35%
-bone cells and protein matrix

Metaphysis:
The region joining the diaphysis to the epiphysis is known as the Metapyhsis and during growth this will contain the cartilage structure known as the growth plate during and is the region in long bones that contains the bulk of the trabecular or cancellous bone.

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3
Q

What type of proteins in bone

A

collagen (Type 1 mostly with some type V) 10-20% water and ~5% non-collagenous protein & carbohydrate.

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4
Q

What can cause bone marrow failure

A

Certain cations rg radium strontium and lead are ‘bone seeking’. They can be radioactive or toxic and cause bone marrow failure.

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5
Q

What are condyles and trochlea

A

Condyles are knuckle shaped and a trochlea is grooved like a pulley

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6
Q

What type of bone on the outside of the shaft and the medullary region

A

Outside: cortical
Inside: bone marrow and trabecular bone

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7
Q

When do bones show in X ray

A

Bone has to be 50% mineralised to be seen on X-ray

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8
Q

Image on slide 7

A

The image shows a lytic poorly circumscribed lesion in the diaphysis which has eroded cortex and caused a periosteal reaction.

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9
Q

Classify cortical vs. cancellous

  1. Where
  2. % of skeleton
  3. Appendicular/axial
  4. % calciied
  5. function

finish

A

..1. Cortical=long bones
Cancellous= vertebrae and pelvis

  1. Cortical= 80% of skeleton, cancellous=20%
  2. Cort.=appendicular cancell=axial
  3. cort=80-90% calcifified, cancell=15-25% calcified
  4. Cort=mainly structural, mechanical, and protective
    cancell=mainly metabolic and large SA
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10
Q

Classify types of anatomical bone

A

Flat (cranial/rib… protect organs), long (femur/tib… support weight and facilitate ovement), short/cupoid (carpals and tarsals, stabalise and facilitate movement), irregular (complex shape like the vertebrae or the pelvis. That allows them to protect a specific organ or set of organs), sesamoid (patella… protective function)

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11
Q

Mascroscopic classification of bone

A

Trabcular/cancellous/spongy

cortical/compact

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12
Q

Microscopic classification of bone

when do you get non-lamellar bone

A

Woven (immature)

Lamellar (mature)

Collagen fibres are laid down in a disorganized fashion: such as states of high bone turnover(Pagets disease of bone, certain stages of fluoride treatment, tumours) not so tightly packed, random bundles

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13
Q

Microanatomy of bone

How big are osteons

Outline the mechanosensory network in bone

A

Osteons=structured, circular layers of lamellar bone, centreed around harvesian canal containing blood vessels … 0.2mm diameter

Circumferential lamaellea near periosteum

Interstital lamellae in between the osteons

Trabecular lamellae not in circular layers, but still lamellar layers

Dendritic structures found in lacunae in the lamellae are bone cells called osteocytes and the processes from them are the osteocyte canalicular network that spans throughout the bone and is thought to form a mechanosensory network allowing the repair of damaged bone or remodeling of structure to respond to new stresses being place on a bone.

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14
Q

Differentiate lamallar vs woven bone.

When might one find woven bone

A

Not in layers, much weaker, collgen disorganised

Woven bone is most often found in the developing skeleton as the cartilage scaffold is first converted to bone, but can also be found in states of rapid grow, or high bone turnover.

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15
Q

Types of bone cell ….and what percentage of them are osteocytes

Which differentiate into what

A

Osteocytes= mechanosensory netweok embedded in mature bone… 90% of bone cells (t1/2=25 years!)

Osteoclasts=multinuclear cells that resorb bone.!! Haematopoietic lineage

Osteoblasts- produce osteoid to form new bone

OSTEOBLAST (produce osteoid around then, which becomes mineralised and then they form)–> OSTEOCYTE

OSTEOCLAST is of haematopoietic lineage

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16
Q

Outline the bone remodelling cycle

PHYSIOLOGICALLY, THEN when some bone is a bit damaged THEN during bone disease

A

PHYSIOLOGICA:
BALANCED osteoclastic bone resorption and osteoblastic bone formation…. these processes are also COUPLED through interactions: osteoblasts mediate osteoclast formation and activity by producing RANKL, M-CSF (MACROPHAGE colony stimulating factor, as osteoclast is a macrophage) and RANKL decoy receptor OPG.

Remodelling occurs when osteocytes sense damage, and also produce RANKL as they apoptose, actvating osteoclasts. These then resorb the old bone, and then die away once they have resorbed to the required depth. Then the reversal phase: osteoblasts are recruited to the site and form new bone with some being trapped to become new osteocytes.

Bone disease then occurs if the balance between osteoclastic resorbtion and osteoblastic bone formation is lost.

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17
Q

What do osteoclasts and osteoblasts look like on sldie 18

A

Osteolast is multinucleated , big

Osteoblasts cuboidal, more flat and on surface

Osteocyte sort of on their own, separate

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18
Q

Indications for bone biopsy

A

Evaluate bone pain or tenderness
Investigate an abnormality seen on X-ray
For bone tumour diagnosis (benign vs malignant)
To determine the cause of an unexplained infection
To evaluate therapy

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19
Q

Types of bone bopsy

Where is typical location for bone biopsy

A

CLOSED - needle, core bopsy (jamshidi needle)

OPEN- for sclerotic/inaccessible lesion (surgery)

Bone biopsy may be performed at any site of interest, but if the reason is general and not bone specific then the typical location would be a transilliac biopsy allowing a core sample with plenty of cortical and trabecular bone to study as shown here.

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20
Q

Types of histological stains

A

H&E (decalcified samples)

Masson-Goldner Trichrome (labels mineralised and unmineralised one)

Tetracycline/calcein leblling (for rate of bone turnover)

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21
Q

What is green on masson-goldner trichrome

How would this differ on osteomalacia

A

Green-mineralised bone

Orange-unmeralied osteoid recently produced by osteoblasts ….

In osteomalacia there would be more orange due to Ca2+ deficiency

22
Q

Explain tetracycline labelling.

A

Green!

Admiistered, incorporated into mineralising front of osteoid currently being mineralised.
Administering it a second time allows us to determine much about the dynamic formation of bone in a patient.

1 line= was only forming bone at the time of 1 injection

2 lines= was forming bone at time of both injections

Distance b/w bone shows how much mineral accrued b/w the 2 injections= MINERAL APPOSITION RATE

Look at mineral apposition rate and quantity of bone surface labelled, to tell you BONE FORMATION RATE (how much bone formed in total in the sample)…

useful for determining if bone turnover is fast, or slow, or if there is a defect in mineralisation

23
Q

What is metabolic bone disease

A

Conditions causing reduced bone mass and strength

Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc)

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

24
Q

Give 3 main categories of metabolic bone disease

as well as

common metabolic bone diseases

A

MAIN TYPES

  1. Related to endocrine abnormality (Vit D; Parathyroid hormone)
  2. Non-endocrine (e.g. age related osteoporosis)
  3. Disuse osteopaenia

COMMON:
Osteoporosis

Osteomalacia/Rickets

Primary hyperparathyroidism

Renal osteodystrophy

Paget’s disease

25
Q

Define osteoporosis

finish

A

BMD T score of -2.5 or lower (through DXA)

means that the patient has a BMD more than 2.5 standard deviations below the population mean BMD at peak bone mass

NOT compared to age, compared to average peak bone mass

26
Q

Primary vs secondary osteoporosis

A

1º - age, post-menopause

2º - nutritional deficits, certain drugs, genetic conditions, and of course endocrine or metabolic disorders

27
Q

2 types of osteoporosis

A

due to imbalance in bone remodelling meaning more resorption than formation:

High turnover- high osteoblastic formation but higher osteoclastic reabsorption

Low turnover- low osteoclast resorption, but lower osteblast bone formation

28
Q

Where is most obvious impact of osteoporosis

A

TRABECULAR BONE

trabeculae tend to be thinner and less interconnected. This weakens the bone and as the osteoporosis progresses there will be a further loss of trabecular bone, the cortical bone will thin and you will see compression fractures in the spine, and low impact fragility fractures in the long bones.

29
Q

Histology of osteoporotic bone

How could you determine if the osteoporosis is high turnover or low turnvoer

A

Masson- Goldner

the trabeculae are thinner and there are fewer than you would expect in normal bone and they will often be ‘free floating’ disconnected from any other bone.

Could then use tetracycline to determine if it is high or low turnover bone.

high turnover osteoporosis as you can see there are large areas of unmineralised osteoid in orange

(presumably unmineralised because bone also formed at a greater rate than it can be mineralised… but the resorption is still greater)
slide 35

30
Q

What is osteomalacia

A

Defective mineralisation of newly synthesised bone

BOTH CALCIUMA ND PHOSPHATE comprise the bone mineral

31
Q

2 types of osteomalacia

A
  1. Deficiency of vitamin D (causing hypocalcaemia)

2 Deficiency of PO4 (phosphate wasting)

32
Q

What will histo look like in osteomalacia

A

Hardly any green… lots of unmineralised osteoid (orange)

As cannot mineralise the osteoid due to calcium deficiency

33
Q

Why does vitamin D lead to osteomalacia

Symptoms of hypocalcaemia

A

We get vitamin D from sunlight exposure and in our diets. Activated Vitamin D acts to increase Calcium absorbtion in the intestine and re-absorbtion in the kidneys so increasing serum calcium levels.

Vit D deficiency from whatever cause results in increased parathyroid hormone (PTH) release and subsequent increased bone resorption.

Hypocalcaemia: muscle twitching, spasms, tingling and numbness…. most common cause it vit D defic.

34
Q

Imaging on osteomalacia

Consequences of osteomalacia

X-ray of rickets

What are looser’s zone fractures

A

Insufficient calcium or phosphate to form the hydroxyapatite crystals necessary to mineralise bone. be observed histologically as the osteoid produced by the osteoblasts remains unmineralised and so orange on this Masson-Trichrome stain.

CONSEQUENCES: 
bone pain/tenderness
fracture
proximal weakness
bone deformity

X-ray: widening of growth plate and bowing of long bones in leg

Looser’s zone: are pseudo-fractures at locations of high tensile stress, normally at right angles to the cortex and extending only part way through the bone

35
Q

What happens in hyperparathyroidism

T/f there is reduced urinary excretion of calcium in primary HPT

What is osteitis fibrosa cystica

A

Excess PTH

F: increased Ca and PO4 excretion in urine

hypercalcaemia

hypophosphataemia

skeletal changes of osteitis fibrosa cystica (Resorption of bone and replacement with fibrous tissue and the formation of cysts like ‘brown tumours)

36
Q

Which organs are affected by PTH

Differentiate calcitriol and PTH in terms of type effect on phosphate and calcium

What happens to ca2+ and phopshate in primary hyperpara.

A

Parathyroid glands
Bones
Kidneys
Proximal small intestine

PTH increases Ca2+ absorption and PO4 excretion

Calcitriol increases absorption of bot Ca2+ and Po4

Normally the serum calcium acts to reduce PTH, but when this feedback mechanism is lost in primary HPT the result is hypercalcemia and hypophosphatemia.

37
Q

Types of hyperparathyroidism

A

1º -
parathyroid adenoma (85-90%)
chief cell hyperplasia

2º -
chronic renal deficiency
vit D deficiency

(i.e. just increases as there’s low vitamin D…)

38
Q

Symptoms of hyperparathyroidism

A

Stones (Ca oxalate renal stones)

Bones (osteitis fibrosa cystica, bone resorption)

Abdominal groans (acute pancreatitis)

Psychic moans (psychosis & depression)

39
Q

Bone lesions in hyperparathyroidism

A

Earliest: Sub periosteal erosions

Tunnel erosions (osteoclasts penetrate the middle of the trabeculae and resorb a central channel)

40
Q

What are brown cell tumours

A

extensive resorption causes lytic bone lesions with reparative tissue called giant cell reparative granuloma. Because the giant cells are often associated with extravasated red blood cells and their brown hemosiderin breakdown products, these tumors have been known as brown tumors

ZONAL pattern distinguishes this lesion from other giant cell containing neoplasms. In addition, giant cell reparative granulomas are not localized to the ends of long bones as are conventional giant cell tumors of bone.

41
Q

A

….

42
Q

What is renal osteodystrophy

A

Comprises all the skeletal changes of chronic renal disease:-

  1. Increased bone resorption (osteitis fibrosa cystica.. due to vit D def. due to chronic renal disease causing secondary HPT)
  2. Osteomalacia (due to hypocalcaemia due to insufficient vit D)
  3. Osteosclerosis
  4. Growth retardation
  5. Osteoporosis
43
Q

Cuases of renal osteosydrophy

A

Consequences of chronic renal disease:-

PO4 retention – hyperphosphataemia

Hypocalcaemia as a result of ↓vit D

2o hyperparathyroidism

Metabolic acidosis

Aluminium deposition

44
Q

3 stages of paget’s disease and how can this disease be described

A

FOCAL disorder of BONE TURNOVER

  1. Osteolytic
  2. Osteolytic-osteosclerotic
  3. Quiescent osteosclerotic
45
Q

Onset, proportion of mono-ostotic vs polyostotic

A
Onset > 40y (affects 3% Caucasians > 55y)
M=F
Rare in Asians and Africans
Mono-ostotic 15%
Remainder polyostotic
46
Q

Cause of paget’s

A

Aetiology is unknown

Familial cases show autosomal pattern of inheritance with incomplete penetrance (mutations in SQSTM1 or RANK)

Parvomyxovirus type particles have been seen on EM in Pagetic bone (doubt.. probably not.. was probs contamination)

Overuse of previous bone injury

47
Q

Symptoms of paget’s disease

A

pain

microfractures

nerve compression (incl. Spinal N and cord)

skull changes
may put medulla at risk

deafness
+/-

haemodynamic changes,

cardiac failure

hypercalcaemia

Development of sarcoma in area of involvement 1%

48
Q

Histology of paget’s

A

Here we see images of a patient diagnosed with Paget’s disease. (A) AP radiograph of the left proximal femur shows increased width of the femoral shaft, markedly thickened cortices, coarse but disorganized trabeculae, and small lytic areas within the medullary canal. (B) The photomicrograph illustrates the active phase of Paget’s disease with numerous trabeculae undergoing resorption by osteoclasts (arrows) and a thin layer of surface-related osteoblasts (arrowheads). Subsequent osteoblastic activity results in cement lines and the “mosaic” pattern apparent in sclerotic phases (Stain, hematoxylin and eosin; original magnification, ×10).

49
Q

Where is pagets most likely to occur

A

Tib, femur, pelvis, humerus, vertebrae, skull

50
Q

What is OPG exactly

A

OPG is a receptor. It competes with RANK for RANKL binding. When it is bound to RANKL, RANK cannot bind to it, so osteocytes cannot mature and thus there is reduced bone resorbsorption

OPG is synthesised in response to oestrogen…. this is lost in the menopause so more RANKL binds RANK and more osteoclasts are activated and more resorption

There is up-regulation of RANK ligand that may occur in response to many stimuli (e.g. infection, trauma etc.).