Endocrine and metabolic bone disorders

Question 1

Differentiate between primary, secondary and tertiary hyperparathyroidism

Answer 1

Primary = PT gland adenoma secreting lots of PTH
Secondary = normal physiological response to low Ca++, start of renal failure
Tertiary = due to chronic low Ca++, PT glands hypertrophy and then become autonomic

Question 2

What form of vitamin D is found in the diet?

Answer 2

Ergocalciferol

Question 3

What foods contain vitamin D?

Answer 3

Oily fish and eggs

Question 4

Where is vitamin D hydroxylated

Answer 4

1. Liver

2. Kidney

Question 5

What enzyme is responsible for the second hydroxylation of vitamin D?

Answer 5

1-alpha-hydroxylase

Question 6

Recall the sequential conversions that lead to vitamin D production from sunlight

Answer 6

7-dehydrocholesterol + UVB –> cholecalciferol –> 25-OH-D3 (liver) –> calcitriol (kidney)

Question 7

Describe the serum calcium, phosphate and PTH and the plasma 25-OH-D3 in primary hyperparathyroidism

Answer 7

Calcium: high
Phosphate: low
PTH: high
25OHD3: low

Question 8

Describe the serum calcium, phosphate and PTH and the plasma 25-OH-D3 in secondary hyperparathyroidism

Answer 8

Calcium: low
Phosphate: high
PTH: high
25OHD3: low

Question 9

Describe the serum calcium, phosphate and PTH and the plasma 25-OH-D3 in tertiary hyperparathyroidism

Answer 9

Calcium: high
Phosphate: high
PTH: high
25OHD3: low

Question 10

What conditions are associated with low vit D?

Answer 10

Children: Rickets
Adults: osteomalacia

Question 11

Differentiate between osteomalacia and osteoperosis

Answer 11

Osteomalacia = vit D deficiency in adults
Osteoperosis = low bone mineral density

Question 12

How are rickets and osteomalacia different?

Answer 12

Rickets = before epiphysial closure therefore growth retardation + skeletal abnormality as well as pain and proximal myopathy
Osteomalacia = after epiphysial closure so no skeletal abnormality but still pain and proximal myopathy

Question 13

What are the 2 main effects of renal failure that affect calcium level?

Answer 13

1. Low calcitrol –> low Ca++ absorption –> hypocalcaemia

2. Low phosphate excretion –> high serum phosphate –> hypocalcaemia

Question 14

How does hypocalcaemia effect bone and what disease state can chronic hypocalcaemia lead to?

Answer 14

Decreases bone mineral density, can lead to (RARE) osteitis fibrosis cystica

Question 15

Recall 4 treatments for OFC

Answer 15

1. Low phosphate diet
2. phosphate-binding drugs
3. ACTIVE d3 analogue
4. parathyroidectomy

Question 16

What drugs are given to replace vitamin D in patients with normal renal function?

Answer 16

Ergocalciferol, cholecalciferol (= inactive D3)

Question 17

What drugs are given to replace vitamin D in patients with renal dysfunction?

Answer 17

1-alpha-hydroxycalciferol (alfacalcidol)

Question 18

What parameter is used to assess osteoperosis and how is this measured?

Answer 18

Bone mineral density T-score

Measured using DEXA scan (Dual Energy X-ray Absorptiometry)

Question 19

Why are post-menopausal women particularly at risk of osteoperosis?

Answer 19

Oestrogen deficiency leads to loss of bone matrix

Question 20

Recall 4 possible endocrine causes of osteoperosis, other than menopause

Answer 20

1. Hypogonadism
2. Cushing’s
3. Hyperthyroidism
4. Primary hyperparathyroidism

Question 21

Recall 2 Iatrogenic causes of osteoperosis

Answer 21

1. Prolonged glucocorticoid use

2. heparin use

Question 22

Recall the 5 possible lines of treeatment for osteoperosis

Answer 22

1. Oestrogen
2. Selective oestrogen receptor modulators
3. Bisphosphonates
4. Denosumab
5. Teriparatide

Question 23

Why is oestrogen used to treat osteoperosis?

Answer 23

Reduces bone resorption

Question 24

What is given in conjunction with oestrogen treatment for osteoperosis, and why?

Answer 24

Progestogen - to prevent endometrial hyperplasia/ cancer

Question 25

Recall 2 concerns with oestrogen treatment of osteoperosis

Answer 25

1. Increased breast cancer risk | 2. Increased risk of thromboembolism

Question 26

What are the 2 types of selective oestrogen receptor moderator drugs? Give an example for each

Answer 26

1. Selective ER antagonist eg tamoxifen | 2. Selective ER agonist eg raloxifene

Question 27

Describe the mechanism of action of bisphosphonates in osteoperosis treatment

Answer 27

1. BP avidly binds to hydroxyapatite 2. Osteoclasts injest hydroxypatite, and BP along with it 3. BP promote osteoclast apoptosis 4. Net reduced bone turnover

Question 28

Recall 3 problems with bisphosphonate treatment

Answer 28

1. Not absorbed well in the gut 2. Often cause oesophagitis 3. Can cause osteonecrosis of jaw

Question 29

What is denosumab?

Answer 29

Human monoclonal Ab

Question 30

What is the mechanism of action of denosumab?

Answer 30

Binds RANK ligands --> prevents osteoclast activity

Question 31

What is teriparatide?

Answer 31

recombinant PTH fragment

Question 32

How is teriparatide administered?

Answer 32

Daily subcut. injection

Question 33

What is Paget's disease of the bone?

Answer 33

Accelerated, localised but disorganised bone remodelling

Question 34

Describe the pathophysiology of paget's disease of the bone

Answer 34

Osteoclastic overactivity --> compensatory increase in dinovosynthesis of bone = structurally disorganised bone with poor tensile strength

Question 35

Recall the clinical features of Paget's disease of the bone

Answer 35

``` Obvious: Arthritis Fracture Pain Deformity Less obvious: Increased vasculatory --> warmth Deafness Radiculopathy (due to bone involvement) ```

Question 36

What is the hallmark biochemical finding in Paget's disease of the bone?

Answer 36

Really high alkaline phosphatase

Question 37

Recall the 2 normal treatmnts for Paget's disease of the bone

Answer 37

Bisphosphonates, analgesia

Question 38

Recall the effector functions of PTH

Answer 38

Promotes bone resorption to release Ca++ Promotes Ca++ reuptake in kidney Phosphorylates inactive Vit D in kidney to calcitriol Decreases renal phosphate resorption

Question 39

Recall the effector functions of Vit D

Answer 39

Increases GUT RESORPTION of Ca++ Promotes bone resorption to release Ca++ (by increasing oesteoblast RANK-L production) Promotes Ca++ re-uptake in kidney

Question 40

Where in the kidney is phosphate resorbed and by what transporter?

Answer 40

PCT | Na+ cotransporter

Question 41

Recall 2 inhibitors of phosphate resorption in the kidney

Answer 41

PTH | FGF23

Question 42

What function is shared by PTH and FGF23

Answer 42

Inhibition of Na+/ PO4--- cotransporter to promote phosphaturia

Question 43

Recall an inhibitor of calcitriol

Answer 43

FGF23

Question 44

Recall how PTH levels are controlled

Answer 44

Ca++ binds parathyroid gland receptors --> negative feedback

Question 45

Recall a cause of Vit D toxicosis

Answer 45

Granulomatous disease

Question 46

Recall the Ca++, phosphate, PTH and ALP in Paget's

Answer 46

Ca++ normal Phosphate normal PTH normal ALP really high