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Endocrine > Calcium and bones > Flashcards

Calcium and bones Flashcards

1
Q

What is the minimum dietary requirement for calcium?

A

12.5mmol/24 hours - higher in growth, pregnancy and lactation

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2
Q

What is the role of an osteoclast?

A
  • mediate bone resorption - activity triggers osteoblast differentiation
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3
Q

What is the role of an osteoblast?

A
  • form new bone - control osteocytes - evolve into osteocytes
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4
Q

What does an osteocyte do?

A
  • sense bone strain or micro fractures - control amount of osteoclast resorption
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5
Q

What is bone tissue made up of?

A
  • osteoid - collagenous organic matrix - hydroxyapetite - osteocytes, osteoclasts, osteoblasts - haversian canals contain vessels, sympathetic and sensory nerves
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6
Q

What hormones control bone growth?

A
  • testosterone and GH stimulate periosteal bone - oestrogen maintains trabecular bone
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7
Q

In what forms does Ca exist in the blood?

A
  • bound to protein (albumin mainly + globulins) - complexed with citrate and phosphate - free ions - physiologically active form
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8
Q

How does alkalosis effect Ca?

A

hydrogen ions dissociate from albumin so Ca binding to albumin increases - fall in free ionised Ca - hypocalcaemia e.g. hyperventilation

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9
Q

How does acidosis effect Ca?

A

hydrogen ions bind to albumin, decreasing binding of Ca - increase in free ionised Ca - hypercalcaemia

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10
Q

What hormones regulate ECF calcium concentrations?

A

PTH and calcitriol (1,25-dihydroxycholecalciferol)

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11
Q

What is the role of PTH?

A
  1. mobilises Ca from bone by increasing osteoclastic reabsorption
  2. increases Ca reabsorption at the renal tubules and decreases phosphate reabsorption at the kidney
  3. increases hydroxylation of vit D to calcitriol, which increases reabsorption of Ca from the gut
  4. decreases bicarb reabsorption
    effect: increased plasma Ca, decreased plasma PO4, acidosis
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12
Q

How is vitamin D metabolised?

A
  1. a photosensitive reaction in the skin results in synthesis of cholecalciferol
  2. Cholecalciferol is hydroxylated in the liver to form 25-(OH)D

(25-hydroxylation) - this is NOT subject to feedback control

  1. PTH stimulated 1 alpha-hydroxylation in the kidney to form calcitriol - 1,25(OH)2D
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13
Q

What is the role of calcitriol?

A
  1. Stimulates caclium and phosphate reabsorption in the gut, increasing Ca and PO4 levels
  2. Promotes bone mineralisation

INCREASED VIT D -> INCREASED Ca and PO4

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14
Q

List the causes of hypercalcaemia (9)

A
  1. Primary hyperparathyroidism
  2. Malignancy
    - these account for 90% of cases
  3. Vit D excess syndromes
    - granulomatous disease: Sarcoid, lymphoma, TB
    - macrophages hydroxylate 25-hydroxycholecalciferol in granumolas (I thought that was interesting and cool)
  4. Immobilisation with high turnover states
    - bed rest, Paget’s disease adolescents
  5. Secondary hyperparathyroidism
  6. PTHrP tumours (acts like PTH but not detected on assay)
  7. Meds
  8. Familial Hypocalciuric hypercalcaemia
  9. Endocrine disorders
    - Hyperthyroidism
    - acute adrenal failure (Addison’s)
  10. Sampling error
    - Assay error, dehydration, tourniquet on
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15
Q

What is the prevalence of primary hyperparathyroidism?

A

1/1000

increases with age

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16
Q

What biochemical pattern is seen in primary hyperparathyroidism?

A

raised Ca

raised or inappropriately normal PTH

low or low/normal PO4 (unless renal failure also present)

ALP raised in the late stages only

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17
Q

What are some other causes of hyperparathyroidism?

A
  1. Parathyroid adenoma - most common
  2. 10% familial
    - MEN type 1: 100% pentrance by age 45-50
    - MEN type 2
    - Familial isolated hyperparathyroidism
    - Familial hypocalciuric hypercalcaemia
  3. Dfifuse hyperplasia of the gland

rarely due to parathyroid Ca

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18
Q

How do you diagnose a parathyroid adenoma?

A

Sestamibi scan +/- US

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19
Q

What is the treatment for primary hyperparathyroidism?

A

If Ca < 3

  • high fluid intake (avoid renal stones)
  • monitor for osteoporosis and development of renal impairment

Surgery indicated if:

  • Ca > 3
  • marked hypercalciuria
  • complications - nephrolithiasis, osteroporosis, renal imp
  • age < 50
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20
Q

What is the pathophysiology behing Familial hypocalciuric hypocalcaemia?

A
  • mutation in the CaSR gene which encodes a calcium sensing receptor in the parathyroid and kidneys
  • there is a perceived hyponatraemia with resultant raised PTH
  • the raised PTH results in hypercalcaemia and hypophosphataemia (sometimes)
  • autosomal dominant
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21
Q

How do you diagnose Familial hypocalciuric hypocalcaemia?

A
  1. FH of mild hypercalcaemia
  2. urine calcium:creatinine ratio of <0.01
  3. urine calcium level of <200mg/24hours (do a 24h urine)
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22
Q

What malignancies release PTHrP?

A

NSCLC, breast, renal, bladder, ovary, head/neck

  • PTHrP has similar activity as PTH but is not detected on the PTH assay
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23
Q

Name some drugs that can cause hypercalcaemia?

A

Vit D excess

Thiazides - mild increase

Lithium - serum Ca normalises on stopping

Antacids - usually chronic high doses w assoc renal impairment “milk alkali syndrome”

Vit A

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24
Q

List the causes of hypocalcaemia

A
  1. Artefact - low albumin (can adjust to a certain extent)
  2. Vit D deficiency/malabsorption
  3. Hypoparathyroidism
  4. CRF (assoc. with high PO4)
  5. Meds: antiepileptics, bisphosphonates
  6. Hypomagnesaemia - impairs PTH secretion & action
  7. Hungry bone syndrome - recent parathyroid surgery
  8. Pancreatitis
  9. Inherited causes: e.g. pseudohypoparathyroidism (tissue PTH resistance)
25
Q

What are the causes of Vit D deficiency?

A
  1. dietry deficiency
  2. malabsorption
  3. inadequate exposure to UV light
26
Q

What are th causes of disordered Vit D metabolism?

A
  1. Renal failure
  2. Anticonvulsant treatment
  3. 1 alpha-hydroxylase deficiency
27
Q

What pattern of PTH, Ca and PO4 do you see in pseudohypoparathyroidism?

A

low calcium

appropriately high PTH (as Ca low)

high phosphate

low calcitriol

The problem is that the PTH receptors are defective so Ca will not increase despite the parathyroids responding appropriately by releasing more PTH

28
Q

What is the pathogenesis behing pseudohypoparathyroidism?

A

Receptor abnormalities of the G protein (inparticular, the Gs alpha subunit) - GNAS1

29
Q

What are the three types of pseudohypoparathyroidism?

A
  • Type 1a: Albright’s hereditary osteodystrophy
    • maternal transmission
    • typical phenotype, developmental delay
  • Type 1b: renal effects only
    • does not have same phenotype
    • maternally transmitted
  • Type 2: genetic defect further down signalling pathway
30
Q

What the hell is pseudopseudohypoparathyroidim then?

A

Where someone looks like they have pseudohypoparathyroidism type 1a (Albright’s heridtary osteodystrophy) but calcium homeostasis is normal

  • paternally transmitted
  • involves the dame GNAS gene
31
Q

What is the difference between osteoporosis and osteomalacia?

A
  • Osteoporosis: there is appropriate mineralisation of osteoid for the degree of bone turnover but the amount of bone tissue is reduced
  • Osteomalacia: there is reduced mineralisation of osetoid and the amount of bone tissue is normal or increased
32
Q

List the causes of osteoporosis

A
33
Q

What are the types and grades of vertebral fractures?

A
34
Q

How do you investigate osteoporosis?

A
35
Q

What is DEXA definition of osteoporosis?

A

T-score less than -2.5

36
Q

Risk factors for osteoporosis

A

Previous fracture

1st degree relative with osteoporosis

Post menomausal female

dementia

Smoking

Low body weight

chronic inflammatory disease

recurrent falls

medications

37
Q

When to consider secondary causes of bone loss?

A

When Z score is less than -2

38
Q

Causes of secondary bone loss

A

Hypogonadism

vitamin D deficiency

Hyperthyroidism

Coeliac disease

Hyperparathyroidism

Multiple myeloma

Medications

Chronic diseases

39
Q

What are bone formation markers

A

Bone specific ALP

osteocalcin

propeptide pf type 1 collagen

40
Q

Markers of bone resorption

A

N-telopeptide

C-telopeptide

urinary free deoxypyridinoline

41
Q

Who to treat for osteoporosis

A

Age over 50 with existing fragility fracture or verterbral fracture

Age over 70 with T score less than -2.5

T score between -1 and 2.5 and FRAX score indicating 20% risk of fracture or 3% risk of hip fracture

Glucocorticoids for greater than 3 months and T score less than -2

Aromatase inhibitors and T score less than -2.5

42
Q

How do glucocorticoids cause osteoporosis

A

Inhibit osteoblasts

Stimular bone resorption

Impair absorption of calcium at gut

Increases urinary calcium loss

Induces secondary hyperparathyroidism

Decreases ovarian and testicular secretion of oestrogens

43
Q

What is controversy about calcium replacement

A

Increased risk of MI

Seems to be safe in doses of 500mg per day

Dietary inake is usually adequate

Only consider if housebound, on steroids, poor dietary intake

44
Q

Dose of vitamin D supplementation

A

Aim for level of 75

Higher levels are not better

best evidence is to give daily supplement of 1000units

45
Q

How do bisphosphonates work?

A

Block enzyme farnesyl pyrophosphate transferase which leads to osteoclast apoptosis, impaired function and decrease in number of osteoclasts

46
Q

Efficacy of different bisphosphonates

A

Alendronate - decrease verterbral and hip # by 50%

Zolendronate - decreased verterbral # by 70% and hip # by 40%

risedronate and etidronate - not as effective

47
Q

How does denosumab work

A

Monoconal ab against rank ligand

Inhibits binding of rank-L to rank, therefore inhibiting ability to form mature osteoclasts

Efficacy - decrease hip and verterbral # by 70%

48
Q

What is teriparitide and how does it work?

A

PTH analogue

Intermittent exposure of PTH to receptors stimulates osteoblastic activity and recruitment, and favours bone formation

Only treatment that increases bone mass

49
Q

Efficacy and use of teriparitide

A

Decreases verterbral # by 65% and non verterbral by 45%

Use for maximum of 2 years (otherwise starts to have osteoclastic effects due to chronic exposure)

Indicated in BMD less than -3, 2 previous fractures and intolerance to bisphosphonates

50
Q

Risk factors for ONJ

A

More common in cancer patients who recieve high doses of anti-resorptive therapies

Age over 65

Periodonitis

Anti-resorptive use greater than 2 years

smoking

Denture wearing

Diabetes

Dental procedures/tooth extractions

51
Q

What are atypical femoral fractures?

A

Stress fractures at mid femur region

Associated with long duration of bisphosphonate use

on XR - medial spike, diffuse cortical thickening, beaking at lateral cortex

Prodromal thigh pain

Commonly bilateral (30%)

52
Q

Features of osteomalacia

A

Insidious onset of aches and pains in lumbar spine, thighs, arms and ribs

Fractures

Myopathy with waddling gait, proximal

low ca, low PO4, high ALP, high PTH

low Vit D

53
Q

Phases of Pagets disease

A

Osteolytic - bone resorption and hypervascularisation

Active bone formation replacing lamellar bone with woven bone

Burnt out - bone resorption declines, leads to hard dense mosaic bone

54
Q

What cell type is prominent in Pagets disease

A

Osteoclast

High concentration

Abnormal number of nuclei

Hyperresponsive to vit D, rank-L, IL6

55
Q

Features of Pagets disease

A

Bone pain

Bowing of tibia/fibula

Vascular steal syndrome - hypervascular bone draws blood away from required sites

Headaches, frontal bossing, cranial nerve palsies, hearing loss from cochlear nerve compression

Fractures

Increased risk of osteosarcomas

High output heart failure due to extensive involvement of skeleton causing AV shunting (rare)

56
Q

Tests in Pagets disease

A

XR - enlargement and expansion of ares of bone with lytic and sclerotic changes

Raised ALP

Elevated bone resorption maerks

Ca/PO4 normal usually

57
Q

Treatment of Pagets

A

Bisphosphonates - zolendronic acid first choice

Second line is calcitonin (suppresses osteoclast activity)

58
Q
A

Endocrine (6 decks)

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