Laboratory investigation of disorders of calcium and phosphate metabolism

Question 1

Osteomalacia - due to

Answer 1

Vitamin D deficiency: most common cause
Usually due to combination of low dietary intake and lack of exposure to sunlight
Elderly at risk, especially if in nursing home and not taking supplements
Breast-fed babies kept out of sunlight

Question 2

Vitamin D - activation

Answer 2

Activated by 2 metabolic steps:

25 hydroxylation in liver to form 25OH
D3, major circulating metabolite

1α hydroxylation of 25 OH D3 in kidney produces 1,25(OH)2 D3, or calcitriol, the active hormone

Question 3

Vit D deficiency - levels of:
Ca
Pi
25 OH D3
1, 25 (OH)2 D3
PTH

Answer 3

Ca = low
Pi = low
25 OH D3 = low
1, 25 (OH)2 D3 = normal 
PTH = high

Question 4

Renal disease - levels of:
Ca
Pi
25 OH D3
1, 25 (OH)2 D3
PTH

Answer 4

Ca = low
Pi = high
25 OH D3 = normal
1, 25 (OH)2 D3 = low
PTH = v. high

Question 5

1α hydroxylase mutation - levels of:
Ca
Pi
25 OH D3
1, 25 (OH)2 D3
PTH

Answer 5

Ca = low
Pi = low
25 OH D3 = normal
1, 25 (OH)2 D3 = v. low
PTH = high

Question 6

Vit D receptor mutation - levels of:
Ca
Pi
25 OH D3
1, 25 (OH)2 D3
PTH

Answer 6

Ca = low
Pi = low
25 OH D3 = normal
1, 25 (OH)2 D3 = v. high
PTH = high

Question 7

X-linked hypopho-phataemic rickets, Autosomal dominant hypopho-phataemic rickets, oncogenic osteomalacia - levels of:
Ca
Pi
25 OH D3
1, 25 (OH)2 D3
PTH
FGF-23

Answer 7

Ca = low/normal
Pi = low
25 OH D3 = normal
1, 25 (OH)2 D3 = low/normal
PTH = high/normal
FGF-23 = high

Question 8

FGF-23 - define

Answer 8

FGF-23: a hormone secreted by osteocytes

Central role in phosphate homeostasis

Question 9

Hypophosphatemic rickets - define

Answer 9

Hypophosphatemic rickets: rare phosphate-wasting conditions leading to bone mineralization defects (osteomalacia)

Question 10

Describe how bone erosion is caused by renal osteodystrophy

Answer 10

↓ renal function
↓ H+ excretion
= metabolic acidosis
= bone erosion

↓ renal function also leads to ↓ 1α,25(OH)2D3
↓ plasma Ca2+
↑ PTH
= bone erosion

Question 11

Renal phosphate reabsorption - done by what and requires what

Answer 11

Sodium-phosphate co-transporter

Requires association with Na-H exchanger regulatory factor (NHERF)