calcium and phosphate metabolism

Question 1

What causes osteoporosis?

Answer 1

• loss of bone mass (mineral and organic matrix)
  causes:
• endocrine
• malignancy
• drug induced
• renal disease
• nutritional
• age

Question 2

Diagnosis of osteoporosis

Answer 2

• measurements of bone mineral density (BMD)
• dual energy x- ray absorptiometry (DEXA or DXA scan)
• T score: number of SDs below average for young adult at peak bone density (

Question 3

What are endocrine causes of osteoporosis?

Answer 3

• hypogonadism - notably any cause of oestrogen deficiency
• excess glucocorticoids - endogenous or exogenous
• hyperparathyroidism
• hyperthyroidism

Question 4

bone density in women at different ages

Answer 4

• menopause = decreased oestrogen = bone density decreases
  -oestrogen promotes osteoblast activity
  osteopenia : start to lose bone mass

Question 5

Treatment for osteoporosis

Answer 5

• adequate calcium and vitamin D intake
• postmenopausal: Hormone Replacement Therapy.
• bisphosphonates - inhibit function of osteoclasts, risedronate, alendronate
• PTH analogues
• Denosumab- human monoclonal antibody against RANK ligand
• Romosozumab - human monoclonal antibody against sclerostin

Question 6

osteomalacia

Answer 6

- loss of bone mineralisation (rickets) 
=> signs and symptoms 
- permanent deformaties in bone 
- diffuse aches and pains 
-chronic fatigue 
-weak bones
-low Ca, Pi 
-elevated alkaline phosphatase 
-PTH may be elevated

Question 7

Causes of osteomalacia

Answer 7

• vitamin D deficiency
• mutations leading to errors in vitamin D metabolism
  -hypophosphatemia
  =>Treatment most commonly involves ensuring adequate Vitamin D and Calcium

Question 8

Regulation of vitamin D (calcitriol)

Answer 8

increased by:
-PTH
-Low Ca
low Pi 
decreased by:
- FGF-23
-high Ca
-high Pi

Question 9

how do vitamin D, PTH and FGF23 maintain plasma calcium and phosphate?

Answer 9

vitamin D deficiency leads to low calcium and low phosphate.
FGF-23 increases renal excretion of phosphate
high PTH = low calcium and low phosphate

Question 10

What is renal osteodystrophy?

Answer 10

Spectrum of conditions associated with bone lesions in renal failure

• impaired pi excretion
• high plasma vitamin D activation
• low plasma calcium
• impaired vitamin D activation
• PTH rises
• excess bone resorption