Biochemistry :part 3

Question 1

State some phosphate-related conditions that cause Rickets/Osteomalacia.

Answer 1

X-linked Hypophosphataemic Rickets (mutation in Phex (this cleaves FGF23))
Autosomal Dominant Hypophosphataemia Rickets
Oncogenic Osteomalacia (mesenchymal tumours can produce FGF23)

Question 2

What can cause osteoporosis due to increased bone resorption and decreased bone formation?

Answer 2

Glucocorticoids

Question 3

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

Answer 3

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

•Remodelling errors. Deeper and more resorption pits

lead to Trabecular perforation

Cortical excess excavation

•Decreased osteocyte sensing

Question 4

Describe the biochemistry of someone with osteoporosis.

Answer 4

Everything should be normal if the cause is primary

Question 5

What is the single best predictor of fracture risk?

Answer 5

BMD

Question 6

What is used to measure BMD?

Answer 6

DEXA scans

Question 7

Which bones are used when measuring BMD and why?

Answer 7

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 8

Which chains make up type 1 collagen?

Answer 8

2 x alpha 1
1 x alpha 2

Question 9

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

Answer 9

Procollagen type 1 N-terminal propeptide (P1NP)

Question 10

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

Answer 10

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 11

After how long do bone resorption markers fall?

Answer 11

4-6 weeks

Question 12

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

Answer 12

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

Question 13

What bone formation marker is commonly in use?

Answer 13

Alkaline Phosphatase

Question 14

What is it used in the diagnosis and monitoring of?

Answer 14

Osteomalacia
Paget’s
Bone Metastases

Question 15

What is P1NP being used for now?

Answer 15

Used as a predictor of response to anabolic treatments

Question 16

What are the two forms of alkaline phosphatase?

Answer 16

Liver
Bone

Question 17

Which bone diseases will cause a rise in ALP?

Answer 17

Osteomalacia
Bone metastases
Also hyperparathyroidism and hyperthyroidism

Question 18

How does alkaline phosphatase change with age?

Answer 18

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

Question 19

What biochemical changes occur in renal osteodystrophy?

Answer 19

Increased serum phosphate
Reduction in calcitriol

Question 20

Describe the sequelae of renal osteodystrophy.

Answer 20

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