Metabolic Bone Disease – Histopathology Flashcards
What are the 4 main functions of bones?
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
What are the two main components of bone and what are their relative proportions?
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
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
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
What are the indications for bone biopsy?
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
What are the two types of bone biopsy?
Closed – needle – core biopsy with Jamshidi needle
Open (surgery) – for sclerotic (osteosclerosis=hardening of bone, needle cannot penetrate through bone) or inaccessible lesions
What are the three types of bone cell?
Osteoblast – build bone by laying down osteoid
Osteoclast – multinucleate cells of the macrophage family that resorb bone
Osteocyte – osteoblast like cells
Where are osteocytes found?
Lacunae (the spaces that contain the osteocytes)- search for a pic.
What cytokine is important for stimulating the differentiation of osteoclast precursors into mature osteoclasts?
M-CSF (this is produced by osteoblasts) osteoclasts are from the macrophage family
Which cells produce RANKL and what is its effect?
(Pre-)osteoblasts
It stimulates the maturation of osteoclasts
RANKL on osteoblasts binds to RANK receptor on osteoclast to activate the osteoclasts
What do mature osteoblasts produce that blocks the RANK/RANKL binding?
Osteoprotegrin (protect the bone by inhibiting osteoclast activation
How are bones classified anatomically?
Flat (cranial bones, ribs etc protective function),
long (femur),
short/cuboid (carpals),
irregular (vertebrae, pelvis, have very specific shape to protect their organs, sesamoid
What type of ossification leads to the formation of:
a. Long Bones
b. Flat Bones
a. Long bones
Endochondral ossification
b. Flat bones
Intramembranous ossification
How else can bone be classified?
Trabecular (cancellous/spongy) or compact (cortical)
Woven (immature) or lamellar (mature)
What is metabolic bone disease?
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.
What are the three main categories of metabolic bone disease?
Related to endocrine abnormality (e.g. Vit D and PTH) Non-endocrine (e.g. age-related osteoporosis) Disuse osteopaenia (disuse= immobilisation)
Describe the staining of calcified and uncalcified bone. (when using Masson - Goldner Trichrome stain)
Calcified/mineralised– green
Uncalcified/unmineralised– orange
What are the primary causes of osteoporosis?
Age
Post-menopause
primary osteoporosis refers to osteoporosis of unknown cause
What are the secondary causes of osteoporosis?
Drugs
Systemic disease
secondary osteoporosis refers to osteoporosis of a known cause
Describe the histology of osteoporotic bone.
Osteoporosis highly affects trabecular bone:
Weak trabecular bridging (trabecular bone= spongy bone)
Holes and cysts
What is osteomalacia and what are its 2 types
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)
Describe the histology of osteomalacia.
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
What are the clinical consequences of osteomalacia?
Bone pain/tenderness
Fracture (horizontal fractures at Looser’s zone at the neck of the femur are commonly seen)
Proximal weakness
Bone deformity
What is used to investigate rate of bone formation?
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
What are the consequences of hyperparathyroidism?
- calcium
- phosphate
- other
Hypercalcaemia (increased Ca2+ reabsorption)
Hypophosphataemia (increased phosphate excretion in the urine)
Osteitis fibrosa cystica (due to increased osteoclast activity)
List the four organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.
Parathyroid glands
Bones
Kidneys
Proximal small intestine
State some causes of primary hyperparathyroidism.
Parathyroid adenoma
Chief cell hyperplasia
State some causes of secondary hyperparathyroidism.
Chronic renal insufficiency
Vitamin D deficiency
What are the symptoms of hyperparathyroidism?
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
What is the most important investigation for hyperparathyroidism and what will it show in someone with hyperparathyroidism?
X-ray of the hand
- firstly, you will see Subperiosteal bone erosions (black holes on x ray due to bone erosion)
- then you will start seeing tunneling erosion (this is when the centre of the trabeculae bone have been eaten away)
- 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
What are the five features of renal osteodystrophy?
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
What is Paget’s disease?
Disorder of bone turnover (there is a lack of proper communication between the cells)
What are the three stages of Paget’s disease?
Osteolytic (osteoclast activity)
Osteolytic-osteosclerotic (osteoclast + osteoblast)
Quiescent osteosclerotic (osteoblast)
Describe the histology and x ray of Paget’s disease.
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
In which ethnicities is Paget’s disease rare?
Asian
African
Which sites does Paget’s disease most commonly affect?
Skull Sternum Spine Humerus Pelvis Femur Tibia
List some clinical features of Paget’s disease.
Pain Microfractures Nerve compression Skull changes Deafness Haemodynamic changes Cardiac failure Hypercalcaemias Development of sarcoma in the area of involvement
What is a Haversian canal?
Channel that blood vessels run in within bone, located at the centre of the osteon
What are Howship’s Lacunae?
Pits in the bone surface where osteoclasts are found (also called resorption bays)
Define osteoporosis and its types
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)
