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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
what release alk phos?
osteoblast
26
what stimulate the release of bone alk phos?
childhood growth, fractures, hyperparathyroidism, paget's disease of the bone
27
what is P1NP precursor of?
type 1 collagen
28
why is P1NP good for detection?
low diurnal & intra-individual variation
29
why is CTx or NTx difficult test to use?
high diurnal and affected by nutrition effects so fasting required before test can be performed
30
what is the normal range for T-scores for DEXA scan?
-1 and above is normal, -1 to -2.5 = osteopenia, -2 or below = osteoporosis
31
What are the risk factors for osteoporosis?
¬ Smoker, Age, Early menopause – lack of oestrogen, Excess alcohol – if more than 20 units per week
32
what is the definition of osteoporosis?
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
how is osteoporosis diagnosed?
DEXA/Xray
34
fragility fracture
a fracture caused by injury that would be insufficient to fracture a normal bone
35
Is myeloma a cause for osteoporosis?
Yes - secondary cause of osteoporosis
36
what are the secondary cause of osteoporosis?
Endocrine - oestrogen related, hypogonadism, hormone ablation for breast/prostate cancer, hyperthyroidism, GI - malnutrition
37
Treatment for osteoporosis?
antiresorptive - bisphosphates, (alendronic acid/zoledronic acid), anabolic - terparatide, synthetic PTH, strontium (mineral good for stimulation of bone formation and slow bone resorption)
38
How does Bisphophonates work?
mimic pyrophosphate structure and taken up by skeleton (which can deposit in bone for years), only come into effect when ingested by osteoclast
39
what is the side-effect of bisphosphonates?
can cause oesophageal/upper GI problems, can cause osteonecrosis of the jaw, atypical femur fractures
40
what are the different types of bone metastases?
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
what are the symptoms of bone metastases?
pain (gradual increase then become constant), broken bones (pathological fractures, common in femurs, humerus), numbness, paralysis etc
42
what cells secrete PTH
chief cells of parathyroid gland
43
cuases of hypercalcaemia?
PTH medicated - sporadic primary hyperparathyroidism & familial, non-PTh mediated - Maglinancy (major cause), Vit D deficiency
44
what is 1o hyperparathyroidism
Ca usually high, PTH inappropriately high, low PO4 & high alk phos
45
what is 2o hyperparathyroidism
Ca normal/high, PTH appropriately high, PO4 high if due to chronic kidney disease, causes - CKD or Vit D deficiency (normal situation)
46
what is 3o hyperparathyroidism
Ca usually high, PTH inappropriately high, PO4 can be high/low ,causes - after prolonged 2o HPT usually in CKD
47
what is a definitive indicative for hyperparathyroidism?
inappropriately elevated PTH in the presence of high Ca
48
Possible causes for 1o hyperparathyroidism?
adenomas (account for 85%), parathyroid carcinoma, glandular hyperplasia (sporadically/genetic syndrome - MEN1, MEN2A or familial hyperparathyroidism), Ectopic adenomas
49
what imaging radioactive isotopes can be used to detect 1o hyperparathyroidism?
Tc 99 Sestamibi
50
what is the function of Calcimimetics (Cinacalcet)?
activate CaSR i nthe parathyroid glands - reduce PTH secretion, normalise Ca in symptomatic patients
51
What is Paget's Disease of the bone?
rapid bone turnover and formation - lead to abnormal bone remodelling
52
what can indicate Paget's Disease of Bone
elevated alkaline phosphatase - increased bone turnover
53
clinical features of Paget's Disease of the bone?
Bone Pain, bone deformity, fractures, arthritis, cranial nerve defects if skull affected, most common affect pelvis, femur and lower lumbar vertebrae.
54
What is osteomalacia
lack of mineralisation of bone due to Vit D deficiency/lack of Ca and/or phosphate
55
what can osteomalacia lead to in child?
Rickets - widened epiphyses & poor skeletal health
56
cause of osteomalacia
insufficient Ca absorption from intestine (dietary deficiency of Ca or Vit D), excessive renal PO4 excretion - rare genetic forms
57
clinical features of osteomalacia
diffuse bone pains, muscle weakness, bone weakness, high alk phos, low Vit D, poss low Ca and high PTH (2o hyperparathyroidism)
58
who is at risk of osteomalacia
nursing home residents, malabsorption, asian pop ( hijab etc)

Endocrine Pathology (5 decks)

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