Biochemistry : part 3

Question 1

How does oestrogen deficiency lead to a decrease in bone mineral density?

Answer 1

It increases the number of bone remodelling units
It causes an imbalance in bone remodelling with increased bone resorption compared to bone formation

Question 2

Describe the biochemistry of someone with osteoporosis.

Answer 2

Everything should be normal if the cause is primary

Question 3

What is the single best predictor of fracture risk?

Answer 3

BMD

Question 4

What is used to measure BMD?

Answer 4

DEXA scans

Question 5

Which bones are used when measuring BMD and why?

Answer 5

Vertebral bodies
 Commonest fracture
 Good measure of cancellous bone
 It is a highly metabolically active bone so it is quick to respond to treatment
Hip – second commonest fracture
NOTE: fracture risk assessment tool (FRAX) uses hip BMD

Question 6

Which chains make up type 1 collagen?

Answer 6

2 x alpha 1
1 x alpha 2

Question 7

What can be used as a marker of bone formation that is linked tocollagen production?

Answer 7

Procollagen type 1 N-terminal propeptide (P1NP)

Question 8

What can be used as a measure of bone resorption that is linked to collagen production?

Answer 8

C-terminal telopeptide (CTX) – serum
N-terminal telopeptide (NTX) – urine
3 hydroxylysine molecules on adjacent tropocollagen fibrils condense to form a pyridinium ring linkage
These can be measured

Question 9

After how long do bone resorption markers fall?

Answer 9

4-6 weeks

Question 10

What are the problems with cross-linking collagen, with regards to measurement of bone markers?

Answer 10

Reproducibility
Positive association with age
Need to correct for creatinine
Diurnal variation in urine markers

Question 11

What bone formation marker is commonly in use?

Answer 11

Alkaline Phosphatase

Question 12

What is it used in the diagnosis and monitoring of?

Answer 12

Osteomalacia
Paget’s
Bone Metastases

Question 13

What is P1NP being used for now?

Answer 13

Used as a predictor of response to anabolic treatments

Question 14

What are the two forms of alkaline phosphatase?

Answer 14

Liver
Bone

Question 15

Which bone diseases will cause a rise in ALP?

Answer 15

Osteomalacia
Bone metastases
Also hyperparathyroidism and hyperthyroidism

Question 16

How does alkaline phosphatase change with age?

Answer 16

Increases markedly during puberty reaching its highest levels
Remains relatively constant following puberty (potential small rise after the age of 50)

Question 17

What biochemical changes occur in renal osteodystrophy?

Answer 17

Increased serum phosphate
Reduction in calcitriol

Question 18

Describe the sequelae of renal osteodystrophy.

Answer 18

Secondary hyperparathyroidism
This is unsuccessful and hypocalcaemia develops
This leads to excessive stimulation of the parathyroid glands, leading to parathyroid hyperplasia
The parathyroid cells begin to reduce expression of calcium-sensing receptors (CSR) and Vitamin D receptors (VDR) and become autonomous (tertiary)
This causes hypercalcaemia