calcium and phosphate metabolism

Question 1

what is osteoporosis and what are the 6 causes

Answer 1

is loss of bone mass( mineral and organic matrix)
causes are:
endocrine
malignancy
drug-induced
real disease
nutritional 
age

Question 2

how is diagnosis of osteoporosis done

Answer 2

measurement of bone mineral density( BMD) using dual-energy X-ray absorptiometry( DEXA OR DXA scan)
T score= number of SDs below average for young adult at peak bone density
Z score=matched to age and/or group

Question 3

what are the t-score of normal, osteoporosis and severe osteoporosis

Answer 3

normal- -1 or above
osteoporosis- -2.5 or lower
severe osteoporosis - -2.5 or lower and presence of at least one fragility fracture

Question 4

endocrine causes of osteoporosis

Answer 4

Hypogonadism — notably any cause of oestrogen 
deficiency 
Excess glucocorticoids — endogenous or 
exogenous 
Hyperparathyroidism 
Hyperthyroidism

Question 5

Treatments for osteoporosis

Answer 5

• Ensure adequate calcium and vit D intake, appropriate
exercise
• Postmenopausal: HRT— effects well established but safety
of long term treatment was questioned in early 2000s
Bisphosphonates — inhibit function of osteoclasts:
risedronate, alendronate
• PTH analogues
• Denosumab — human monoclonal antibody against RANK ligand
• Romosozumab— human monoclonal antibody against
sclerostin (very recent)

Question 6

what is osteomalacia

Answer 6

loss of bone mineralization (termed rickets in children

Question 7

signs and symptoms of osteomalacia

Answer 7

permanent deformations in bone growth (rickets)
diffuse aches and pains 
chronic fatigue
weak bones 
low Ca, Pi
Elevated alkaline phosphate 
PTH may be elevated

Question 8

causes of osteomalacia

Answer 8

Vit D deficiency (most common)
mutation leading to error in vit d metabolism (rare)
hypophosphatemia

Question 9

what 3 things increase calcitriol synthesis

Answer 9

PTH
Low Ca
Low Pi

Question 10

what 3 things decrease calcitriol synthesise

Answer 10

FGF-23
High Ca
High Pi

Question 11

what is the principle effect of FGF-23

Answer 11

increase phosphate excretion

it is secreted when there is high level of phosphate

Question 12

What is FGF-23

Answer 12

a hormone secreted by osteocytes

Question 13

Disorders to do with osteomalacia and hypophosphatemia

Answer 13

oncogenic (tumour secreting FGF-23)
X-linked hypophosphatemia rickets
autosomal dominant hypophosphatemia rickets (gain of function mutation)

Question 14

what does decrease renal function cause in reference to phosphate

Answer 14

decreased renal function means increase phosphate concentration. this leads to inhibition calcitriol production. Which leads to reduced calcium level and increased PTH levels which can cause bone erosion

Question 15

what is renal osteodystrophy

Answer 15

its a blanket term used to cover spectrum of conditions associated with bone lesions in renal failure and these include:

• impaired Pi excretion
• high plasma Pi
• Impaired Vit D activation
• Low plasma Ca
• PTH rises
• Excess bone reabsorption
• May be augmented by acidosis (impaired renal H+ excretion)