Metabolic Bone Disease – Histopathology

Question 1

What are the 4 main functions of bones?

Answer 1

STRUCTURE
give structure and shape to the body
MECHANICAL
sites for muscle attachment
PROTECTIVE
Protects vital organs and bone marrow
METABOLIC
reserve of calcium and other minerals

Question 2

What are the two main components of bone and what are their relative proportions?

Answer 2

Inorganic (65%) – calcium hydroxyapatite (store of 99% of the body’s calcium, 85% of the phosphorous and 65% of Na and Mg)
Organic (35%) – bone cells and protein matrix

Question 3

Compare the Cortical and cancellous bones

• which bones contain more of them
• % of skeleton
• where on the skeleton contains most of these bones
• degree of calcification
• functions
• surface area

Answer 3

Cortical  
 makes up the bulk of your Long bones 
 80% of skeleton 
 Appendicular skeleton 
80-90% calcified 
 Mainly mechanical and protective role 
Cancellous 
 makes up the most of your Vertebrae and pelvis bones
 20% of skeleton  
 Axial  
15-25% calcified  
 Mainly metabolic 
 Large surface  area

Question 4

What are the indications for bone biopsy?

Answer 4

Most of the time, you don’t need to do it because eg x rays is suffice
Confirm the diagnosis of a bone disorder
Find the cause of or evaluate ongoing bone pain or tenderness
Investigate an abnormality seen on X-ray
For bone tumour diagnosis (benign vs malignant)
To determine the cause of an unexplained infection
To evaluate therapy performance

Question 5

What are the two types of bone biopsy?

Answer 5

Closed – needle – core biopsy with Jamshidi needle
Open (surgery) – for sclerotic (osteosclerosis=hardening of bone, needle cannot penetrate through bone) or inaccessible lesions

Question 6

What are the three types of bone cell?

Answer 6

Osteoblast – build bone by laying down osteoid
Osteoclast – multinucleate cells of the macrophage family that resorb bone
Osteocyte – osteoblast like cells

Question 7

Where are osteocytes found?

Answer 7

Lacunae (the spaces that contain the osteocytes)- search for a pic.

Question 8

What cytokine is important for stimulating the differentiation of osteoclast precursors into mature osteoclasts?

Answer 8

M-CSF (this is produced by osteoblasts) osteoclasts are from the macrophage family

Question 9

Which cells produce RANKL and what is its effect?

Answer 9

(Pre-)osteoblasts
It stimulates the maturation of osteoclasts
RANKL on osteoblasts binds to RANK receptor on osteoclast to activate the osteoclasts

Question 10

What do mature osteoblasts produce that blocks the RANK/RANKL binding?

Answer 10

Osteoprotegrin (protect the bone by inhibiting osteoclast activation

Question 11

How are bones classified anatomically?

Answer 11

Flat (cranial bones, ribs etc protective function),
long (femur),
short/cuboid (carpals),
irregular (vertebrae, pelvis, have very specific shape to protect their organs, sesamoid

Question 12

What type of ossification leads to the formation of:

a. Long Bones
b. Flat Bones

Answer 12

a. Long bones
Endochondral ossification
b. Flat bones
Intramembranous ossification

Question 13

How else can bone be classified?

Answer 13

Trabecular (cancellous/spongy) or compact (cortical)

Woven (immature) or lamellar (mature)

Question 14

What is metabolic bone disease?

Answer 14

A group of diseases caused by the imbalance of various chemicals in the body (vitamins, hormones, minerals etc) which leads to altered bone cell activity, rate of mineralisation or changes in bone structure. Ultimately, it leads to reduced bone mass and bone strength.

Question 15

What are the three main categories of metabolic bone disease?

Answer 15

Related to endocrine abnormality (e.g. Vit D and PTH) 
Non-endocrine (e.g. age-related osteoporosis) 
Disuse osteopaenia (disuse= immobilisation)

Question 16

Describe the staining of calcified and uncalcified bone. (when using Masson - Goldner Trichrome stain)

Answer 16

Calcified/mineralised– green

Uncalcified/unmineralised– orange

Question 17

What are the primary causes of osteoporosis?

Answer 17

Age
Post-menopause

primary osteoporosis refers to osteoporosis of unknown cause

Question 18

What are the secondary causes of osteoporosis?

Answer 18

Drugs
Systemic disease

secondary osteoporosis refers to osteoporosis of a known cause

Question 19

Describe the histology of osteoporotic bone.

Answer 19

Osteoporosis highly affects trabecular bone:
Weak trabecular bridging (trabecular bone= spongy bone)
Holes and cysts

Question 20

What is osteomalacia and what are its 2 types

Answer 20

Condition of defective bone mineralisation that can be caused by:
2 types:
1. Calcium deficiency (as a result of vitamin D def)
2. Phosphate deficiency (caused by phosphate wasting syndromes)

Question 21

Describe the histology of osteomalacia.

Answer 21

No calcification of bone
More uncalcified osteoid (osteoid= uncalcified bone)
Bones are very bendy and cannot carry musculature very easily
mineralisation gives bones the ‘strength’ and the organic part gives it its flexibility

Question 22

What are the clinical consequences of osteomalacia?

Answer 22

Bone pain/tenderness
Fracture (horizontal fractures at Looser’s zone at the neck of the femur are commonly seen)
Proximal weakness
Bone deformity

Question 23

What is used to investigate rate of bone formation?

Answer 23

Fluorescent tetracycline labelling
Tetracycline is incorporated into mineralizing bone and can be detected by its fluorescence.[13] In “double tetracycline labeling”, a second dose is given 11–14 days after the first dose, and the amount of bone formed during that interval can be calculated by measuring the distance between the two fluorescent labels

Question 24

What are the consequences of hyperparathyroidism?

• calcium
• phosphate
• other

Answer 24

Hypercalcaemia (increased Ca2+ reabsorption)
Hypophosphataemia (increased phosphate excretion in the urine)
Osteitis fibrosa cystica (due to increased osteoclast activity)

Question 25

List the four organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.

Answer 25

Parathyroid glands
Bones
Kidneys
Proximal small intestine

Question 26

State some causes of primary hyperparathyroidism.

Answer 26

Parathyroid adenoma

Chief cell hyperplasia

Question 27

State some causes of secondary hyperparathyroidism.

Answer 27

Chronic renal insufficiency

Vitamin D deficiency

Question 28

What are the symptoms of hyperparathyroidism?

Answer 28

Stones, Bones, Abdominal Groans and Psychic Moans
Stones – calcium oxalate renal stones
Bones – osteitis fibrosa cystica
Abdominal Groans – acute pancreatitis (stones block secretion and the enzyme zymogens build up in pancreas)
Psychic Moans – psychosis and depression

Question 29

What is the most important investigation for hyperparathyroidism and what will it show in someone with hyperparathyroidism?

Answer 29

X-ray of the hand

1. firstly, you will see Subperiosteal bone erosions (black holes on x ray due to bone erosion)
2. then you will start seeing tunneling erosion (this is when the centre of the trabeculae bone have been eaten away)
3. Hyperparathyroidism causes osteitis fibrosa cystica, one of the main features of OFC is Brown cell tumours (these are not actual tumours, but fibrous tissue that has replaced the original tissue) see slide 48 notes for more details

Question 30

What are the five features of renal osteodystrophy?

Answer 30

It Comprises of all the skeletal changes resulting from chronic renal disease as a result of failure to excrete phosphate and produce vitamin D

Increased bone resorption (osteitis fibrosa cystica)  
Osteomalacia  
Osteoporosis 
Osteosclerosis  
Growth retardation

Question 31

What is Paget’s disease?

Answer 31

Disorder of bone turnover (there is a lack of proper communication between the cells)

Question 32

What are the three stages of Paget’s disease?

Answer 32

Osteolytic (osteoclast activity)
Osteolytic-osteosclerotic (osteoclast + osteoblast)
Quiescent osteosclerotic (osteoblast)

Question 33

Describe the histology and x ray of Paget’s disease.

Answer 33

sclerosis (thickening) of the outer cortical areas of the bones (x ray)

at the same time, there are osteolytic regions in the bone as well (black on x ray)

high bone turnover in the histology of early paget’s disease: you will see osteoclasts breaking down a lot of bone and osteoblasts forming new bone

Question 34

In which ethnicities is Paget’s disease rare?

Answer 34

Asian

African

Question 35

Which sites does Paget’s disease most commonly affect?

Answer 35

Skull 
Sternum 
Spine 
Humerus 
Pelvis 
Femur  
Tibia

Question 36

List some clinical features of Paget’s disease.

Answer 36

Pain 
Microfractures  
Nerve compression  
Skull changes  
Deafness  
Haemodynamic changes  
Cardiac failure  
Hypercalcaemias 
Development of sarcoma in the area of involvement

Question 37

What is a Haversian canal?

Answer 37

Channel that blood vessels run in within bone, located at the centre of the osteon

Question 38

What are Howship’s Lacunae?

Answer 38

Pits in the bone surface where osteoclasts are found (also called resorption bays)

Question 39

Define osteoporosis and its types

Answer 39

Defined as a bone mineral density T-score of -2.5 or lower (patient has a BMD 2.5 standard deviations lower than the mean for their sex)

types:
2 types- 
High turnover (inceased activity of osteoclast and osteoblast but osteoclast is higher relative to osteoblast and so overall=resorption)  vs low turnover (dampening down of both osteoclast and osteoblast activity, but the osteoblast activity was reduced more than the osteoclast activity and so overall= bone resorption)