Bone and new markers

Question 1

What part of the bone is corticoid bone?

Answer 1

Hard, out layer

Question 2

What part of the bone is the trabecular bone?

Answer 2

Spongy, inner layer

Question 3

What do osteoblasts do?

Answer 3

Secrete bone

Question 4

What do osteoclasts do?

Answer 4

absorb bone

Question 5

What is the function of the trabecular bone?

Answer 5

Bone marrow -

-Haemopoesis

Question 6

What is the extracellular part of bone composed of?

Answer 6

Inorganic matrix - hydroxyapatite, minerals e.g. calcium, phosphate

Organic matrix - collagen

Question 7

What is bone before it is mineralised?

Answer 7

Osteoid

Question 8

What mineralises bone?

Answer 8

Hydroxyapatite

calcium-phosphate, hydroxide salt

Question 9

Why is bone considered a dynamic tissue?

Answer 9

Constantly being remodelling

High vascular

Metabolically active

Osteoblasts produce and secrete metric and help with mineralisation

Osteoclasts reabsorb (both clasts/blast actions = linked)

Question 10

What do osteoblasts do?

Answer 10

Make osteoid (non-mineralised organic matrix - mainly collagen)

Make hormones (osteocalcin), matrix proteins and alkaline phosphatase

Question 11

What are osteoblasts called when buried underneath/trapped within matrix?

Answer 11

Osteocytes

Question 12

What enzymes do osteocytes produce?

Answer 12

Tartrate resistant acid phosphatase (TRAP)

Cathespin K

Question 13

What main hormone is osteoclasts regulated by?

Answer 13

PTH

Question 14

What ligands/proteins helps with osteoclast maturation and activity

Answer 14

RANK (produced by osteoblasts)

Osteoprotegrin

Question 15

What are the function of osteocytes?

Answer 15

Maintain bone matrix turnover

Question 16

What is the bone remodelling process?

Answer 16

Osteocyte -> reabsorption pit -> osteoblast -> produce osteoids -> mineralisation (hydroxyapatite) -> osteocyte

Question 17

Why is reduced bone mass related to menopause?

Answer 17

Loss of oestrogen

Question 18

What also happens as you get older (i.e. osteoclastic - osteoblastic activity)

Answer 18

Osteoclastic activity increases - balance tipped to bone reabsorption

Question 19

What diagnostic test is used to investigate bone gross structure?

Answer 19

X-rays

Question 20

What investigative technique is used to assess bone mass? (I.e. calcium levels)

Answer 20

DEXA scan

Question 21

What biomarkers indicate bone formation (i.e. pro-osteoblastic activity)

Answer 21

Osteocalcin

Pro collagen type I phosphatase (P1NP)

Alkaline phosphatase

Question 22

What markers could be used for bone reabsorption

Answer 22

Cross linked telopeptides of type 1 collagen (CTX/NTX)

Question 23

What markers could be used for osteoclastic activity? (i.e. enzymes)

Answer 23

TARP (tartrate acted resistant phosphatase)

Cathespin K

Question 24

What produces alkaline phosphatase?

Answer 24

Osteoblasts - indicator of bone remodelling

Question 25

When is high levels of all pos observed?

Answer 25

- Fractures - Hyperthyroidism - Pagets disease of bone

Question 26

What is pro collagen type I phosphatase an indicator of? what is it a particularly good marker?

Answer 26

Indicates osteoblastic activity Good because it is a very stable marker - no diurnal variation/no affected by food intake

Question 27

What does cross linked telopeptides of Type I collagen indicate? What can their use be problematic?

Answer 27

Indicates bone reabsorption e.g. adolescence, menopause, hyperthyroidism However diurnal variation/affected by food intake

Question 28

What are the problems with using bone markers?

Answer 28

Not disease specific Not specific - type I collagen which is widely distributed in body Intra-individual variability

Question 29

What is a DEXA scan used to determine? What do the T scores indicate

Answer 29

Bone mass/density T score - number of SD's away normal = -1+ Osteopenia = -1 - -2.5 Osteoporosis =

Question 30

What are the risk factors for osteoporosis?

Answer 30

``` Age Early menopause Malnutrition Alcohol/smoking Steroids ```

Question 31

What is osteoporosis? What is it marketed by?

Answer 31

Generalised loss of bone Reduced bone mass + deranged bone architecture = failure of structural integrity (propensity to fracture) Lighter X-ray, DEXA scan (

Question 32

What is a fragility fracture?

Answer 32

Fracture of bone by force that would usually be insufficient to fracture a normal bone (minimal trauma)

Question 33

What anti-reabsorptive drug is used to treat osteoporosis? what cell does it act on?

Answer 33

Bisphosponates Anti-resorptive - osteoclasts

Question 34

What anabolic drug is used to treat osteoporosis? What cell does it act on?

Answer 34

Terparatide Anabolic - synthetic PTN

Question 35

Where are the common places for bone metastasis occur?

Answer 35

``` Femur spine pelvis skull Humerus ```

Question 36

What are the two types of bone metastasis? Where do they originate from usually?

Answer 36

Lytic - osteoclastic breakdown - lung/breat Sclerotic - osteoblastic - deposition of new bone =- prostate, lymphoma, breast/lung

Question 37

What are the symptoms of bone metastasis?

Answer 37

- Pain - Fractures - Paralysis, numbness, trouble urinating - spinal cord compression - Hypercalcaemia - thirsty, loss of appetite, confusion, fatigue - anaemia - disrupted bone marrow function

Question 38

What are the symptoms of hypercalcaemia?

Answer 38

``` Polyuria/polydipsa Dehydration Fatigue Confusion Mood disturbance Nausea Abdo pain Vomiting Coma Dehydration Cardiac arrthymias ```

Question 39

What are the main causes of hypercalcaemia?

Answer 39

- Malignancy | - Hyperparathyroidism

Question 40

What regulates blood calcium? What is produced and by what cells?

Answer 40

Parathyroid gland Produces PTH by chief cells

Question 41

What does PTH do?

Answer 41

increases Ca in blood by increasing decomposition of bone, and increasing absorption from intestines and kidney

Question 42

What other factors act on the parathyroid gland?

Answer 42

``` Vit D (low increase PTH) Magnesium ```

Question 43

What is secondary hyperparathyroidism usually caused by?

Answer 43

Vit D deficiency (marked by normal calcium levels but too high PTH)

Question 44

What is tertiary hyperparathyroidism usually caused by?

Answer 44

When secondary hyperparathyroidism has gone on for too long

Question 45

What is primary hyperparathyroidism usually caused by?

Answer 45

Calcium and PTH inappropriately high Disease of

Question 46

What are the main causes of primary parathyroidism

Answer 46

Adenoma - chief cells producing too much PTH Also parathyroid carcinoma - malignant - aggressive but rare Hyperplasia of glands - sporadic or genetic (MEN1, MEN2a, familial hyperparathyroidism) Ectopic adenomas

Question 47

What are the clinical manifestations of primary hyper parathyroidism?

Answer 47

- Renal failure - Hypercalcaemia - Bone disease - proximal muscle wasting

Question 48

What is the treatment for PHPT?

Answer 48

Surgery Cinacalcet - activates the CaSR receptor - results in reduced PTH secretion

Question 49

What is Pagets disease? What is it marked by?

Answer 49

Excessive bone turnover and formation resulting in abnormal remodelling - Marked by elevated Alkaline phosphatase

Question 50

What are the clinical features of Paget's disease?

Answer 50

- Bone pain - Bone deformity - Fractures - Arthritis - Risk of osteosarcoma - Pelvis, femur, lumber vert

Question 51

Whats the best treatment for pages disease?

Answer 51

Bisphosphonates - slow down osteoclasts

Question 52

What is the osteomalacia commonly referred to as?

Answer 52

Rickets

Question 53

What is osteomalacia usually caused by?

Answer 53

Lack of mineralisation of osteoid Insufficient calcium absorption from intestine e.g. lack of dietary calcium or vit D deficiency Excessive renal excretion of phosphate

Question 54

What are the presentations of osteomalacia?

Answer 54

- Symmetrical bone pain - Muscle weakness - Bone weakness - Low Ca, low bit D - Secondary hyperparathyroidism

Question 55

What is the biochemistry (increase/decreased Alk pos, Ca, phosphate, PTH) for the following conditions... a) HyperPTH b) osteomalacia c) osteoporosis d) Pagets e) Bone mets

Answer 55

a) High alk phos, high calcium, low phosphate, high PTH b) High alk phos, low calcium, low phosphate, high PTH c) no change d) high alk phos, e) high alk phos, high calcium, low PTH