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Endocrine Pathology > CP51 - Diseases of Bone and Application > Flashcards

CP51 - Diseases of Bone and Application Flashcards

1
Q

What are the bone composition?

A

Cortical bone, trabecular bone, cells, extracellular matrix

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2
Q

what is cortical bone

A

hard & outer layer

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3
Q

what is trabecular bone

A

spongy & inner layer

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4
Q

what cells are present in the bone

A

osteoblast, osteoclast

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5
Q

what is in the extracellular matrix

A

organic matrix (mainly collagen), inorganic component ( hydroxyapatite & minerals)

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6
Q

is bone in a constant dynamic state?

A

yes - constant renewal of bones - in adult renew every 10 years

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7
Q

what is osteoblast

A

bone forming cells which is terminally differentiated products of mesenchymal stem cells

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8
Q

what does osteoblast do?

A

make osteoid (non-mineralised organic matrix, consist of mainly type 1 collagen), make hormones eg osteocalcin, alkaline phosphate, prerequisite for mineralisation of osteoid

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9
Q

what are osteoblast which are being buried within the matrix called?

A

osteocytes

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10
Q

what is osteoclasts?

A

large multi-nucleated cells which breaks down bone

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11
Q

what enzyme does OC make?

A

tartrate resistant acid phosphate (TRAP) & cathepsin K

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12
Q

what do TRAp & cathepsin k do?

A

break down extracellular matrix

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13
Q

what is the function of osteoclast?

A

help enhance blood Ca level (regulated by PTH, calcitonin & IL-6)

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14
Q

what helps with osteoclastic maturation & activity?

A

RANK ligand & osteoprotegrin

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15
Q

what is osteocytes

A

osteoblast buried in the matrix & involved in regulating bone matrix turnover

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16
Q

what is the process of bone formation/reabsorption?

A

osteoclast precursor attach to bone - activation of osteoclast - resorption of bone - take place - osteoblast precursor bound - bone formation by osteoblast - mineralisation of the bone - repeat

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17
Q

does bone density decrease with age?

A

yes - rapid growth during puberty, peak at 20s-30s, plateau for 10-20 years, decrease from then on

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18
Q

what is the effect oestrogen on bone density?

A

ostrogen used to maintain bone health and so menopause will cause bone loss

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19
Q

what can be used to investigate bone diseases?

A

X-ray, DEXA (bone mass), biochemistry (cellular function/turnover), Biopsy & qCT (microstructure & cellular function)

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20
Q

what are the most common biochemical marker for bone formation?

A

Pocollagen Type 1 N Propeptides (P1NP)

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21
Q

what is the most common biochemical marker used to test for bone resoption?

A

Crosslinked telopeptides of type 1 collagen - NTX, CTX

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22
Q

what are the specific osteoclast enzyme test?

A

TRAP & cathepsin K

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23
Q

when should specific isoenzyme for alk phos be used?

A

to determine where is alk phos come from as 50 in liver, 50 in bone

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24
Q

what is the function of bone alk phos?

A

phosphate involved in mineralisation of bone

25
Q

what release alk phos?

A

osteoblast

26
Q

what stimulate the release of bone alk phos?

A

childhood growth, fractures, hyperparathyroidism, paget’s disease of the bone

27
Q

what is P1NP precursor of?

A

type 1 collagen

28
Q

why is P1NP good for detection?

A

low diurnal & intra-individual variation

29
Q

why is CTx or NTx difficult test to use?

A

high diurnal and affected by nutrition effects so fasting required before test can be performed

30
Q

what is the normal range for T-scores for DEXA scan?

A

-1 and above is normal, -1 to -2.5 = osteopenia, -2 or below = osteoporosis

31
Q

What are the risk factors for osteoporosis?

A

¬ Smoker, Age, Early menopause – lack of oestrogen, Excess alcohol – if more than 20 units per week

32
Q

what is the definition of osteoporosis?

A

systemic skeletal disease characterised by low bone mass and microachitecturarl deterioration of bone tissue wth consequent increase in bone fragility and susceptibility to fracture (decreased bone mass + deranged bone microarchitecture = failure of structural integrity)

33
Q

how is osteoporosis diagnosed?

A

DEXA/Xray

34
Q

fragility fracture

A

a fracture caused by injury that would be insufficient to fracture a normal bone

35
Q

Is myeloma a cause for osteoporosis?

A

Yes - secondary cause of osteoporosis

36
Q

what are the secondary cause of osteoporosis?

A

Endocrine - oestrogen related, hypogonadism, hormone ablation for breast/prostate cancer, hyperthyroidism, GI - malnutrition

37
Q

Treatment for osteoporosis?

A

antiresorptive - bisphosphates, (alendronic acid/zoledronic acid), anabolic - terparatide, synthetic PTH, strontium (mineral good for stimulation of bone formation and slow bone resorption)

38
Q

How does Bisphophonates work?

A

mimic pyrophosphate structure and taken up by skeleton (which can deposit in bone for years), only come into effect when ingested by osteoclast

39
Q

what is the side-effect of bisphosphonates?

A

can cause oesophageal/upper GI problems, can cause osteonecrosis of the jaw, atypical femur fractures

40
Q

what are the different types of bone metastases?

A

1) lytic - destruction of normal bone especially common in breast/lung, kidney/thyroid 2) sclerotic/osteoblastic - deposition of new bone especially in prostate, lymphoma, breast/lung

41
Q

what are the symptoms of bone metastases?

A

pain (gradual increase then become constant), broken bones (pathological fractures, common in femurs, humerus), numbness, paralysis etc

42
Q

what cells secrete PTH

A

chief cells of parathyroid gland

43
Q

cuases of hypercalcaemia?

A

PTH medicated - sporadic primary hyperparathyroidism & familial, non-PTh mediated - Maglinancy (major cause), Vit D deficiency

44
Q

what is 1o hyperparathyroidism

A

Ca usually high, PTH inappropriately high, low PO4 & high alk phos

45
Q

what is 2o hyperparathyroidism

A

Ca normal/high, PTH appropriately high, PO4 high if due to chronic kidney disease, causes - CKD or Vit D deficiency (normal situation)

46
Q

what is 3o hyperparathyroidism

A

Ca usually high, PTH inappropriately high, PO4 can be high/low ,causes - after prolonged 2o HPT usually in CKD

47
Q

what is a definitive indicative for hyperparathyroidism?

A

inappropriately elevated PTH in the presence of high Ca

48
Q

Possible causes for 1o hyperparathyroidism?

A

adenomas (account for 85%), parathyroid carcinoma, glandular hyperplasia (sporadically/genetic syndrome - MEN1, MEN2A or familial hyperparathyroidism), Ectopic adenomas

49
Q

what imaging radioactive isotopes can be used to detect 1o hyperparathyroidism?

A

Tc 99 Sestamibi

50
Q

what is the function of Calcimimetics (Cinacalcet)?

A

activate CaSR i nthe parathyroid glands - reduce PTH secretion, normalise Ca in symptomatic patients

51
Q

What is Paget’s Disease of the bone?

A

rapid bone turnover and formation - lead to abnormal bone remodelling

52
Q

what can indicate Paget’s Disease of Bone

A

elevated alkaline phosphatase - increased bone turnover

53
Q

clinical features of Paget’s Disease of the bone?

A

Bone Pain, bone deformity, fractures, arthritis, cranial nerve defects if skull affected, most common affect pelvis, femur and lower lumbar vertebrae.

54
Q

What is osteomalacia

A

lack of mineralisation of bone due to Vit D deficiency/lack of Ca and/or phosphate

55
Q

what can osteomalacia lead to in child?

A

Rickets - widened epiphyses & poor skeletal health

56
Q

cause of osteomalacia

A

insufficient Ca absorption from intestine (dietary deficiency of Ca or Vit D), excessive renal PO4 excretion - rare genetic forms

57
Q

clinical features of osteomalacia

A

diffuse bone pains, muscle weakness, bone weakness, high alk phos, low Vit D, poss low Ca and high PTH (2o hyperparathyroidism)

58
Q

who is at risk of osteomalacia

A

nursing home residents, malabsorption, asian pop ( hijab etc)

Endocrine Pathology (5 decks)

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