Biochemistry: part 1

Question 1

What is P1NP being used for now?

Answer 1

Used as a predictor of response to anabolic treatments

Question 2

What is used to measure BMD?

Answer 2

DEXA scans

Question 3

What is the half-life of PTH?

Answer 3

8 mins

Question 4

What is the normal range for serum calcium concentration?

Answer 4

2.15-2.56 mmol/L

Question 5

Which receptors/proteins are involved in mediating the effects of calcitriol on the intestines?

Answer 5

TRPV6
Calbindin

Question 6

Describe the effect of metabolic alkalosis on calcium distribution.

Answer 6

It makes more calcium bind to plasma proteins thus reducing the free calcium levels
NOTE: venous stasis may elevate free calcium

Question 7

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

Answer 7

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

Question 8

How many amino acids make up PTH and which part of this is active?

Answer 8

84
Active: N1-34

Question 9

Which bone diseases will cause a rise in ALP?

Answer 9

Osteomalacia
Bone metastases
Also hyperparathyroidism and hyperthyroidism

Question 10

Describe the effects of calcitriol on bone and in the kidneys.

Answer 10

Facilitates PTH effect on the DCT in the kidneys (increased calcium reabsorption)
Synergises with PTH in the bone to increase osteoclast activation/maturation

Question 11

Briefly describe the bone remodelling cycle.

Answer 11

A microcrack crosses the canaliculi and severs the osteocyte processes, inducing osteocyte apoptosis
This signals to the surface lining cells, which release factors to recruit cells from the blood and marrow to the remodelling compartment
Osteoclasts are generated locally and resorb the matrix and the mitrocrack
Then osteoblasts deposit new lamellar bone
Osteoblasts that become trapped in the matrix become osteocytes

Question 12

What are the clinical features of primary hyperparathyroidism?

Answer 12

Stones, Bones, Abdominal Groans and Psychic Moans
Stones – renal colic, nephrocalcinosis
Bones – osteitis fibrosa cystica
Abdominal moans – dyspepsia, pancreatitis, constipation
Psychic groans – depression, impaired concentration
NOTE: patients may also suffer fractures secondary to the bone resorption
IMPORTANT NOTE: hypercalcaemia also causes diuresis (polyuria and polydipsia)

Question 13

What is metabolic bone disease?

Answer 13

A group of disease that cause a change in bone density and bone strength by increasing bone resorption, decreasing bone formation or altering bone structure

Question 14

State some signs and symptoms of Rickets.

Answer 14

Symptoms:
 Lack of play
 Bone pain and tenderness (axial)
 Muscle weakness (proximal)
Sign:
 Age dependent deformity
 Myopathy
 Hypotonia
 Short stature
 Tenderness on percussion

Question 15

Which cells produce this factor?

Answer 15

Osteoblast lineage cells

Question 16

What parameter is used to determine whether a patient is vitamin D deficient?

Answer 16

Deficient < 20 ng/M (50 nmol/L)
Normal > 30 ng/M (75 nmol/L)

Question 17

What else can the PTH receptor be activated by other than PTH?

Answer 17

PTHrP (PTH related protein)
This is produced by some tumours

Question 18

What is PTH dependent on?

Answer 18

Magnesium

Question 19

Describe the effects of PTH in:

a. Bone
b. Kidneys

Answer 19

a. Bone
Acute release of available calcium (not stored in hydroxyapatite crystal form)
More chronically, increased osteoclast activity
b. Kidneys
Increased calcium reabsorption
Increased phosphate excretion
Increased stimulation of 1-alpha hydroxylase (thus increasing calcitriol production)

Question 20

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

Answer 20

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