L29: Calcium & Phosphate Metabolism

Question 1

How is osteoporosis diagnosed?

Answer 1

→Measurement of bone mineral density (BMD)

→Dual-energy X-ray absorptiometry (DEXA or DXA scan)

Question 2

What are the stages of osteoporosis?

Answer 2

→osteopenia
→osteoporosis
→severe osteoporosis

Question 3

What are the causes of osteoporosis?

Answer 3

→Hypogonadism – notably any cause of oestrogen deficiency

→Excess glucocorticoids – endogenous or exogenous- Cushing’s syndrome

→Hyperparathyroidism- excess resorption

→Hyperthyroidism

Question 4

Why does oestrogen decreased after menopause?

Answer 4

→no more follicles

Question 5

What are the treatments for osteoporosis?

Answer 5

→Bisphosphonates

→PTH analogues

Question 6

How is osteoporosis treated in postmenopausal?

Answer 6

→HRT

Question 7

How does Denosumab treat osteoporosis?

Answer 7

→human monoclonal antibody against RANK ligand

Question 8

What is bisphophonate?

Answer 8

→inhibit function of osteoclasts: risedronate, alendronate- reduce rate of bone turnover

Question 9

How does romosozumab treat osteoporosis?

Answer 9

→human monoclonal antibody against sclerostin

→Sclerostin inhibits Wnt signalling

Question 10

What is osteomalacia?

Answer 10

→Loss of bone mineralization

Question 11

What are symptoms of osteomalacia?

Answer 11

→Permanent deformities in bone growth (rickets)

→Diffuse aches and pains

→Chronic fatigue
Weak bones

Question 12

What is elevated in osteomalacia?

Answer 12

→Elevated alkaline phosphatase- enzyme marker for bone turnover

Question 13

What is a difference between osteoporosis and osteomalacia?

Answer 13

→osteoporosis is when there is loss of organic and mineralisation

Question 14

What are the causes of osteomalacia?

Answer 14

→Vitamin D deficiency (most common), lack of Vit D supplements or sunlight exposure

→Mutations leading to errors in vitamin D metabolism (rare)

→Hypophosphataemia

Question 15

In VitD deficiency, what are the levels of Ca, Pi, 25OHD3, 1,25OH, PTH?

Answer 15

→Ca- low
→Pi- low
→25 OH D3- low
→1, 25 OH D3- normal
→PTH- high

Question 16

In renal disease, what are the levels of the hormones?

Answer 16

→Ca- low
→Pi- high
→25 OH D3- normal
→1, 25 OH D3- low
→PTH- very high

Question 17

In 1a hydroxylase mutation (Ricket’s type 1)?

Answer 17

→Ca- low
→Pi- low
→25 OH D3- normal
→1, 25 OH D3- normal
→PTH- high

Question 18

In 1a hydroxylase mutation (Ricket’s type 2)?

Answer 18

→Ca- low
→Pi- low
→25 OH D3- normal
→1, 25 OH D3- very high
→PTH- high

Question 19

What is VitD dependent rickets type 1?

Answer 19

→1α hydroxylase mutation1

Question 20

What is VitD dependent rickets type 2?

Answer 20

→Vit D receptor mutation

Question 21

What are the three disorders as a result of osteomalacia and hypophosphataemia?

Answer 21

→X-linked hypopho-phataemic rickets

→Autosomal dominant hypopho-phataemic rickets

→Oncogenic osteomalacia

Question 22

Which cells secrete FGF23?

Answer 22

→osteocytes

Question 23

Why does mutation in FGF23 cause excess phosphate excretion?

Answer 23

→Mutation changes proteolytic sequence so FGF-23 remains in circulation for longer

Question 24

What are the clinical manifestations of renal osteodystrophy?

Answer 24

→Impaired Pi excretion
→High plasma Pi
→Impaired Vit D activation
→Low plasma Ca because of less absorption
→PTH rises
→Excess bone resorption
→May be augmented by acidosis (impaired renal H+ excretion

Question 25

What does acidosis favour?

Answer 25

→bone mineralisation