Bone Metabolism

Question 1

Of the bone matrix, what two things does the organic component consist of?

Answer 1

Type 1 Collagen

Non-collagenous proteins i.e. Osteonectin, Osteopontin, Osteocalcin

Question 2

Of the bone matrix, what does the inorganic component consist of?

Answer 2

Calcium hydroxyapatite

Question 3

What is Trabeculae also known as?

Answer 3

Spongy bone, or cancellous bone

Question 4

How is Trabeculae very light yet has a large surface area?

Answer 4

The bone marrow has been removed from the bone, leaving pores and “bite marks” which increases the surface area

Question 5

What are the two types of cells involved in bone resorption and deposition?

Answer 5

Osteoclasts and Osteoblasts

Question 6

What is the function of Osteoclasts?

Answer 6

Bone resorption (bone removal)

Question 7

What is the function of Osteoblasts?

Answer 7

Bone deposition (bone laying down)

Question 8

Describe what is meant by the phrase “use it or lose it” in the context of bones

Answer 8

Bones are use-dependent and will reduce in mass in zero gravity / no exercise. 1% of bone mass is lost every month in zero gravity, whereas weight bearing exercises will not only increase muscles but also bones

Question 9

How much calcium is found within the human body?

Answer 9

1,000 g

Question 10

What is the normal serum concentration of calcium?

Answer 10

2.25 - 2.6 mmol/L

Question 11

Ionised calcium is serum is rigidly maintained by what?

Answer 11

Parathyroid hormone (PTH), Vitamin D, Calcitonin

Question 12

What does coupled bone remodelling refer to?

Answer 12

Bone deposition = Bone resorption

Question 13

The components of bone matrix are % organic / % inorganic?

Answer 13

40% organic

60% inorganic

Question 14

Describe the cellular structure of OsteoCLASTS

Answer 14

Large and multinucleated, with up to 40 - 100 nuclei. The more nuclei, the more aggressive they resorb

Question 15

Describe the cellular structure of OsteoBLASTS

Answer 15

Mononuclei, stromal, non-haematopoetic and mesenchymal

Question 16

Describe what the role of Osteoblasts are in some detail

Answer 16

Osteoblasts produce Type 1 Collagen which will eventually mineralise into bone matrix

The osteoblasts bury themselves alive in bone matrix as osteocytes, and make connections with other osteocytes via cell extensions

Question 17

Describe what the role of Osteoclasts are in some detail

Answer 17

Osteoclasts sit on the bone surface and form limpet-like adhesions via integrins. They secrete enzymes and acids to degrade bone matrix forming lacunae

Question 18

What is the recommended daily intake of Calcium?

Answer 18

1,000 mg

Question 19

Protein-bound calcium (40% of serum Ca) is bound to…?

Answer 19

Albumin

Question 20

Complexed calcium (10% of serum Ca) is complexed to…?

Answer 20

Citrate and Phosphate

Question 21

How much Phosphorus is located in the body?

Answer 21

600 g

Question 22

What is the normal range for Phosphate levels?

Answer 22

0.9 - 1.3 mmol/L

Question 23

What are the Phosphate levels in serum primarily regulated by…?

Answer 23

Parathyroid hormone

Question 24

What is Vitamin D3 also known as?

Answer 24

Cholecalciferol

Question 25

Cholecalciferol can be ingested in the diet, but also synthesised de novo. How?

Answer 25

Synthesised in the skin from 7-dehydrocholesterol using UV light

Question 26

How is Cholecalciferol converted to 25(OH) Vitamin D3 (inactive)

Answer 26

Via 25-hydroxylation in the liver

Question 27

How does 25(OH) Vitamin D3 (inactive) become 1,25 (OH) Vitamn D3 (active)

Answer 27

Via 1-hydroxylation in the kidneys

Question 28

The synthesis of 1,25(OH) Vitamin D3 is tightly regulated... How?

Answer 28

Synthesis is regulated by PTH | Inhibition is regulated by increased Ca+ and P in serum

Question 29

What is the purpose of 1,25(OH) Vitamin D3?

Answer 29

Increases calcium and phosphate absorption from the intestine and into the blood Can also induce marrow monocytes to differentiate into osteoclasts to stimulate bone resorption

Question 30

How does Vitamin D3 become catabolised?

Answer 30

Via 24-hydroxylation

Question 31

What is Parathyroid Hormone secreted by?

Answer 31

Parathyroid gland

Question 32

Parathyroid hormone is secreted in response to...?

Answer 32

Low Calcium levels in serum

Question 33

Describe the effects of high and low PTH on the skeleton

Answer 33

High levels of PTH: Osteoclastic bone resorption, mobilising calcium FROM bone Low levels of PTH: Osteoblastic bone deposition, mobilising calcium TO bone

Question 34

How does the PTHRP usually work, systemically or locally? What about pathologically?

Answer 34

Normally: Local effect Pathologically: Systemically when secreted in excess during malignancy

Question 35

Calcitonin is released from...? In response to...? What effect does it have...?

Answer 35

Parafollicular cells of the thyroid In response to increased plasma calcium Causes reduced bone resorption

Question 36

What two sex hormones are important in bone metabolism?

Answer 36

Oestrogens | Androgens

Question 37

What is the incidence of Osteoporosis in men and women over 50?

Answer 37

Women: 1 in 2 Men: 1 in 5

Question 38

State five treatments for Osteoporsis

Answer 38

``` Calcium supplementation Hormone Replacement Therapy Bisphosphonates Calcitonin Selective Estrogen Receptor Modulators ```