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Year 2 LCRS Musculoskeletal > 1-3: Metabolic Bone diseases > Flashcards

1-3: Metabolic Bone diseases Flashcards

1
Q

What is the composistion of bone?

A
  1. 65% inorganic material
    • ​​calcium hydroxyapatite (Ca10(PO4)6(OH)2)
    • 99% of Calcium, 85% of the Phosphorus, 65% Sodium, Magnesium in body
  2. Organic
    • Bone cells
    • Matrix (Collagen)
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2
Q

What is the epiphysis, metaphysis and diaphysis of bone?

A
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3
Q

How can you devide bones anatomically?

A

Into

  • long
  • sesamoid
  • flat
  • short/cuboid
  • irregular

bones

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4
Q

How can you classify bone Macroscopically?

A

Can devide into

  1. trabecular/cancellous/spongy bone
  2. Cortical/compact bone
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5
Q

How can you classify bone on a microscopic level?

A
  1. Lamellar (mature) bone
  2. Woven (immature) bone
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6
Q

What is calcellous bone?

A

Trabercular Bone

  • 20% of human skeleton
  • axial (center of body)
  • highly metabolic active
  • large surface area
  • 15-20% calcified
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7
Q

What is cortical bone/skeleton?

What are its characteristics?

A

Long bones

  • appendicular
  • 80-90% calcified
  • mainly structural, mechanical, and protective
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8
Q

Explain the microanatomy of cortical bone

A
  1. Osteons (made up of several concentric lamellar) surrounding a central canal
  2. All surrounded by a Circumferential lamellae
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9
Q

Explain the microanatomy of cancellous bone

A

Trabecular bone

  • Made up of interconnected trabeculae
  • All arranged in lamellars (but without central canal)
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10
Q

What is the role of osteocytes?

How do they fulfill this function in the bone remodeling cycle?

A
  1. They are the “brain of the bone”, embedded in mature bone and sense damage
  2. If damage sensed: activation of immature osteoclasts via apoptosis + RANKL receptor
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11
Q

What is the role of osteoclasts?

What are their characteristics?

What is their function in the bone remoddling cycle?

A

Are multinuclear cells that resorb/remove bone

  • get activated via RANKL/RANK
  • Resorb damaged/old bone
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12
Q

What are osteoblasts?

What is their role in the bone-remodelinc cycle?

A

produce osteoid to form new bone

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13
Q

Identify the different bone cells

A
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14
Q

What are the riasons why you would perform a bone biopsy?

A
  1. Confirm the diagnosis of a bone disorder
  2. Find the cause of or evaluate ongoing bone pain or tenderness
  3. Resolve problems that can’t the solved by radiology alone
    • 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 performance
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15
Q

What are the different types of bone biopsy that can be performed?

A
  1. Closed
    • needle
    • for core biopsy
  2. Open
    • for inacessible/large areas
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16
Q

What is the most commonest site for bone biopsy?

Why?

A

A transiliac biopsy because all types of bone can be seen

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17
Q

Which stains are available for bone biopsys?

What are they used for respectively?

A
  1. H&E
  2. Masson - Goldner Trichrome
    1. mineralised vs unmineralised bone
  3. Tetracycline/Calcein labelling
    1. bone turnover (2 flourescent injection with a break ov several days –> dye is incorporated into bone –> measure thickness between 2 lines)
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18
Q

What is oeteoporosis (per definition)?

A

Defines as BMD (bone mieral density) of T-score -2.5 SDV (T-score= peak bone mass in 25 Yr old)

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19
Q

What is the difference between primary and secondary osteoporosis?

A
  1. Due to age+ menopause
  2. Due to drugs, systenic disease
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20
Q

What is the difference between high and low turnover osteoporosis?

A

Osteoporosis generally: more bone is resorbed than produced

High turnover= a lot is produced but even more resorbed

Low turnover= little production and a little more resorbtion

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21
Q

Which part of the bone is primarily affected by osteoporosis?

How?

A

Mainly the trabercular bone

–> fewer, thinner and free floatin trabercular bone sections

22
Q

What are the histological findings of osteoporotic bone?

A

Fever, thinner free floating trabercular bone

(Histopathology might be useful in determining high vs. low turnover disease but for diagnosis/ follow up biochemistry + imaging more useful)

23
Q

What are the radiological abnormalities you can observe in osteoporosis?

A
  1. Loss of cortical bone/thinning of cortex
  2. Loss of trabeculae
  3. Codfish vertebrae
  4. Insufficiency fractures
    • areas of increased uptake of a bone scan due to stress fracture
    • bone oedema
  5. Sclerosis: attempted healing of fractured bone
24
Q

What is a “cod fish vertebra”?

When can it be seen?

A

Biconcave deformity of vertebrae Seen in

  • Osteoporosis
  • Osteomalacia
25
Q

What is a looser zone?

A

Pseudo/insufficicnecy fractures at high tensile stress areas

  • Medial proximal femur
  • Lateral scapula
  • Pubic rami
  • Posterior proximal ulna  Ribs
26
Q

What is the difference between an insuficiency fracture and a looser zone?

A

Looser zone are a sub-type of insufficiency fractures (= normal force on abnormal bone causes fracture) that usually only traversing part way through a bone, usually at right angles to the involved cortex

Looser zones are associated with osteomalacia and rickets

27
Q

Which biochemical tests would you perform to investigate osteoposis?

Why?

A

Mainly to exclude other reasosn:

In primary osteoporosis all findings should be normal (there might be high uring Ca2+ levels) but exclude

  • Vit D: deficiency
  • any 2nd endocrine causes
    • Primary hyperparathyroitidsm (high PTH)
    • hyperthyroidism (high T3, supressed TSH)
    • Hypogonadism (low Testosterone)
  • Exclude multiple myeloma
28
Q

What is osteomalacia/rickets?

What are the commonest reasons?

A

Failure to mineralise immature (woven) bone–> normally due to

  1. Vit D deficiency
  2. PO4 deficiency
29
Q

What are the histopathological finding in osteomalacia?

A

Increased unmineralised/ woven bone

30
Q

What are the radiological finding in rickets?

A

Rickets= osteomalacia before growth plate closes

  1. Osteopenia, Looser’s zone, Codfish vertebrae, Bending deformities
  2. +
  3. Indistinct/frayed metaphyseal margin
  4. Widened growth plate without calcification
  5. Cupping/splaying metaphyses due to weight

bearing

  1. Enlargement of anterior ribs
31
Q

What are the radiological signs in osteomalacia?

A

Mature skeleton

  • Osteopenia
  • Looser’s zones
  • Codfish vertebrae
  • Bending deformities
32
Q

How would the biochemical findings look in Someone with rickets/ osteomalacia?

A
  1. Calcium N/low
  2. Phosphate N/low
  3. Alk phos High
  4. 25(OH)Vit D Low
  5. PTH High (secondarily to compensate)

•Urine

  • Phosphate High
33
Q

What are the signs and symptoms of a child with rickets?

A

Lack of play, often due to

  • Bone pain and tenderness (axial)
  • Muscle weakness (proximal)
  • Age dependent deformity
  • Myopathy
  • Hypotonia
  • Short stature
  • Tenderness on percussion
34
Q

What is the effect and role of FGF-23?

A

It is involved in regulating phosphate levels

  • produced by osteoclasts
  • trigger PO4 excretion
  • inhibit Vit D activation
35
Q

What are the biochemical findings of someone with primary hyperparathyroidism?

A
  1. High Ca2+
  2. High PTH
  3. Low Po4
  4. High Vit D
36
Q

What are the radiological finding in someone with Hyperparathyroidism?

A

Causes increased bone resorbtion leading to

  1. Subperiosteal
    • irregular bone borders
  2. Subchondral
    • dark areas below chondyles
  3. Intracrotical
  4. “Brown tumours”–> osteitis fibrosa cystica (replacement of bone matrix with connective tissue)
37
Q

What is renal osteodystrophy?

A

It is a combination of skeletal changes resulting from chronic renal disease

38
Q

Explain the effects and clinical features of renal osteodystrophy

A
  1. Increased bone resorption (osteitis fibrosa cystica)– Osteomalacia
  2. – Osteosclerosis
  3. – Growth retardation
  4. – Osteoporosis
39
Q

What are the radiological changes that can be seen in renal osteodystrophy?

A
  1. Osteomalacia and osteoporosis
  2. Secondary hyperparathyroidism
    • Subperiosteal erosions, brown tumours
    • Sclerosis – vertebral endplates giving a rugger jersey spine
    • Soft tissue calcification (vessels, cartilages)
40
Q

What would be the biochemical findings in Pagets disease?

A

Increased Alkaline phosphatase, otherwise normal (might have increased Ca2+) (+increased bone formation)

41
Q

What would be the radiological findings in Pagets disease?

A
  1. Cortical thickening
  2. Bone expansion
  3. Coarsening of trabeculae
  4. Osteolytic, osteoclerotic and mixed lesions
  5. Osteoporosis circumscripta
    • cranial loss of bones/cycts
42
Q

What are the different stages of Pagets disease?

A
  1. Osteolytic
  2. Osteolytic-osteosclerotic
  3. Quiescent osteosclerotic
43
Q

What are the histological finding in someone with pagets disease?

A

Dependant on the phase:

  1. thickened cortex
  2. high number of osteoclasts
  3. woven bone
44
Q

What are the clinical symptoms of someone with Pagets 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%
45
Q

What is the difference between pathology and a radiological signs?

A

A Pathology

  • A disease process that gives rise to symptoms, signs,biochemical disturbances and changes in imaging appearance.

Radiological sign

  • A change in imaging appearance, whether structural or functional, that may point towards a pathology
46
Q

Which test are run in a bone profile?

A
  1. Calcium
  2. Corrected calcium
  3. Phosphate
  4. Alkaline Phosphatase
47
Q

What is corrected calcium?

A

It takes into account the total calcium and the albumnin levels (–> if low albumin levels–> calcium will be higher for that patient)

48
Q

What is the role of Alkaline phosphatase?

A

There is a liver and a bone form

It is involved in:

  • essential for mineralisation
  • regulates concentrations of phosphocompounds

–> often high in conditions with high bone formation (Osteomalacia, Bone metastases, Hyperparathyroidism, Hyperthyroidism)

49
Q

Explain the effect of Calcium in the loop of Henle

A

Basically acts like a loop diuretic:

Inhibits the Cl+/NA+/K+ cotransporter for reabsorbtion of water and ions

–> Induces diuresis

50
Q

What is the Fanconi syndrome?

A

It is damage to the proximal tubule of the kidney resulting in

  1. causes phosphaturia
  2. stops 1α hydroxylation of Vit D

due to

  • multiple myeloma
  • heavy metal poisoning: lead, mercury
  • drugs: tenofovir, gentamycin
  • congenital disease: Wilsons, glycogen storage diseases
51
Q

Which biochemical marker of bone formation and resorbtion can be used in the monitoring of osteoporosis treatment?

Explain its origin

A

Formation

  • P1NP = Procollagen type 1 N-terminal Propeptide, measured in blood (terminal ends of collagen precursor –> not used anymore
  • but Mainly Alkaline Phosphatase

Resorbtion

  • serum CTX
  • urine NTX –> crossliks of collagen molecules that are released during bone break down

Year 2 LCRS Musculoskeletal (9 decks)

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