Diseases of Bone and Application of New Markers

Question 1

What are the two layers of bone and what are they like?

Answer 1

Cortical bone - hard outer layer, makes up 80% of bone. Forms columns that hold vessels/nerves
Trabecular bone - spongy inner layer that holds bone marrow

Question 2

What separates the cortical and trabecular layers of bone?

Answer 2

endosteum

Question 3

What are the extracellular components of bone?

Answer 3

collagen
hydroxyapatite
calcium, phosphate

Question 4

What are osteoblasts?

Answer 4

outside of bone
already mineralised
makes osteroid (bone)
makes hormones, matrix proteins and alkaline phosphatase
get buried/trapped within the matrix = osteocytes

Question 5

What are osteoclasts?

Answer 5

reabsorbs bone
critical for repair and maintenance of bone
increases blood Ca levels
regulate hormones: parathyroid hormone, calcitonin and IL-6

Question 6

What are osteocytes?

Answer 6

buried/trapped osteocytes

regulates bone matrix turnover

Question 7

What is osteoid?

Answer 7

Bone cell before it has been mineralised

Question 8

Explain the process on normal bone remodelling

Answer 8

Osteoclasts dissolve the collegen and reabsorb the bone
Osteoblasts lay down osteoids
Osteoids become mineralised = osteoblasts
some osteoblasts become trapped = osteocytes
cycle repeats

Question 9

What are the 2 main biochemical marker of bone formation?

Answer 9

Alkaline phosphatase

Procollagen type I propeptides (P1NP)

Question 10

What is the biochemical marker for bone degredation products of bone collagen?

Answer 10

Crosslinked telopeptides of type I collagen (NTX, CTX)

Question 11

What are the 2 biochemical marker that are osteoclast enzymes?

Answer 11

Tartrate-resistant acid phosphatase (TRACP 5b)

Cathepsin K

Question 12

Alkaline phosphatase (APA) is a marker for which two organs of the body?

Answer 12

Bone and liver

Specific isoenxymes can be measured when there is a diagnostic doubt

Question 13

What does raised APA signify and in what conditions is it raised?

Answer 13

increased = increased bone remodelling/repair

Growing children
Fractures
Hyperparathyroidism - primary/secondary
Pagets disease of the bone

Question 14

Why is P1PN a good marker and when does it increase?

Answer 14

Stable levels for a long time
do not need to fast the patient
increase = increased osteoblast activity

Question 15

When does NTX and CTX increase?

Answer 15

Increase = periods of high turnover, crosslinking molecule that correlates highly with bone resorption
Hyperthyroidism, adolescents, menopause

Question 16

What is DEXA imaging used for?

Answer 16

look at bone mass and density
small amount of radiation used
Lumbar spine/hip mostly imaged

Question 17

What is a T score and what does it signify?

Answer 17

Amount of bone density - not age related
-1 and above = normal
Between -1 and -2.5 = osteopenia
-2.5 and below = osteoporosis

Question 18

What are the features of osteoporosis?

Answer 18

Inside the bone: thin cortex, plate compression, loss of trabecular network, wedge fractures, sclerosis
kyphosis
increased chest infections
bloating
ALP, P1PN normal as not sensitive enough, must be diagnosed via DEXA

Question 19

What are the risk factors for osteoporosis?

Answer 19

female
age
smoker
alcohol
menopause
lack of absorption of nutrients e.g. ulcerative colitis/colonectomy
steriods
Vit D deficiency

Question 20

What is a fragility fracture?

Answer 20

fracture caused my a low force that wouldn’t normally affect bone
Common sites: spine, neck of femur, wrist

Question 21

What are examples of antiresrptive treatments? i.e. reduces bone breakdown

Answer 21

Bisphosphonates e.g. Alendronic acid

Denosumab

Question 22

What drug is an anabolic method of treating low bone density?

Answer 22

Terparatide - synthetic PTH

Question 23

What is bisphosphonates mechanism of action?

Answer 23

Similar structure to pyrophosphate
Inhibiting activation of enzymes that utilize pyrophosphate
Attach to Ca and accumulate on bone
Taken up by the osteoclasts

Question 24

What are the side effects of bisphosphonates?

Answer 24

poor absorption
difficult to take - must stay upright for a certain amount of time after taking it
oesophageal/upper GI problems
flu-like side effects
osteonecrosis of the jaw - necrosis/infection of jaw
atypical femur fracture

Question 25

What are the 2 catagories of bone metastases?

Answer 25

Lytic - destruction of normal bone | Sclerotic/Osteoblastic - deposition of new bone

Question 26

What are the features of a patient with metastatic compression of the spinal cord?

Answer 26

``` Back pain - worse at night, gets better with movement initially broken bones numbness Oliguria Vomiting loss of appetite confusion fatigue anaemia known to have cancer Ca elevated dehydrated/thirst ```

Question 27

What is checked in anyone with a high Ca level?

Answer 27

PTH

Question 28

What are the symptoms of hypercalcaemia?

Answer 28

``` polyuria/polydipsia mood disturbances anorexia nausea/vomiting fatigue constipation abdo pain coma pancreatitis dehydration arrhythmias ```

Question 29

What cells in which part of the body secrete parathyroid hormone?

Answer 29

chief cells | parathyroid gland in neck

Question 30

How is parathyroid hormone regulated?

Answer 30

Low Ca → parathyroid gland releases PTH → decomposition of bone, increased Ca absorption from intestines, reabsorption of Ca from urine → increased Ca → negative feedback via Vit D

Question 31

What are Ca and PTH levels in primary, secondary, tertiary hyperparathyroidism?

Answer 31

Primary: ↑ Ca and PTH Secondary: ↓ Ca, ↑PTH Tertiary: ↑ Ca and PTH - happens after HPT has occurred chronically so PT forgets how to work

Question 32

What diseases can cause primary hyperparathyroidism?

Answer 32

Adenomas - can be ectopic Carcinomas (rare) Glandular hyperplasia - all 4 glands enlarged, usually genetic

Question 33

What are the clinical signs of primary hyperparathyroidism?

Answer 33

hypercalcaemia symptoms renal disease - inc stones Bone disease muscle wasting

Question 34

What are the treatment options for primary hyperparathyroidism?

Answer 34

surgery | Calcimimetics - reduced PTH secretion

Question 35

What is Pagets disease of the bone and what are the signs and symptoms?

Answer 35

Rapid bone turnover and formation → abnormal remodelling = high ALP arthritis painful fractures Cranial nerves may be affected - hearing/vision loss risk of osteosarcoma

Question 36

What investigations are used to detect Pagets disease?

Answer 36

Lab assessment plain X ray Nuclear medicine bone scan

Question 37

What is the treatment option for Pagets disease and how can it be monitored?

Answer 37

bisphosphonates | measure ALP and NTX

Question 38

What is osteomalacia?

Answer 38

Lack of mineralisation of the bone due to Vit D/phosphate/Ca deficiency usually in children

Question 39

What are the clinical features of osteomalacia?

Answer 39

bone pain muscle weakness bone weakness high ALP

Question 40

What would be the ALP, Ca, P and PTH levels for HyperPTH, Osteomalacia, Osteoporosis, Pagets and Bone metastasis?

Answer 40

``` HyperPTH: ↑ ALP, ↑ Ca, ↓ P, ↑ PTH Osteomalacia: ↑ ALP, Ca, ↓ P, PTH Osteoporosis: all normal Pagets: ↑ ALP, normal Ca, P and PTH Bone Mets: ↑ ALP, ↑ Ca, normal P, ↓ PTH ```