Metabolic Bone Disease – Histopathology Flashcards
What are the three main functions of bones?
Mechanical – support and site for muscle attachment
Protective - vital organs and bone marrow
Metabolic – reserve of calcium
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
Describe the classification of bone as cortical and cancellous.
Cortical
- Long bones
- 80% of skeleton
- Appendicular skeleton
- 80-90% calcified
- Mainly mechanical and protective role
Cancellous
- Vertebrae and pelvis
- 20% of skeleton
- Axial
- 15-25% calcified
- Mainly metabolic
- Large surface area
What are the indications for bone biopsy?
- 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 – for sclerotic 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
What cytokine is important for stimulating the differentiation of osteoclast precursors into pre-osteoclasts?
M-CSF (this is produced by osteoblasts)
Which cells produce RANKLigand and what is its effect?
Pre-osteoblasts
It stimulates the maturation of osteoclasts
What do mature osteoblasts produce that blocks the RANK/RANKL binding?
Osteoprotegrin
competitive inhibitor of RANK
How are bones classified anatomically?
Flat
Long
Cuboid
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?
-functionally
Trabecular (cancellous) or compact (cortical)
-architecturally
Woven (immature) or lamellar (mature)
What is metabolic bone disease?
Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc.)
Overall effect is reduced bone mass (osteopaenia) often resulting in fractures from little or no trauma
What are the three main categories of metabolic bone disease?
- Endocrine abnormality (e.g. Vit D and PTH)
- Non-endocrine (e.g. age-related osteoporosis)
- Disuse osteopaenia
Describe the staining of calcified and uncalcified bone.
Calcified – green
Uncalcified – orange
What are the primary causes of osteoporosis?
Age
Post-menopause
(physiological)
What are the secondary causes of osteoporosis?
Drugs
Systemic disease
(pathological)
Describe the histology of osteoporotic bone.
Weak trabecular bridging
Holes and cysts
What is osteomalacia and what can it be caused by?
-Defective mineralisation of normally synthesized bone matrix
causes:
1. Vitamin D deficiency
2. Phosphate deficiency (usually related to chronic renal disease)
What are the metabolic and endocrine consequences of vitamin D deficiency?
Secondary hyperparathyroidism –> increased bone resorption
Hypocalcaemia – neuronal excitability causing muscle twitching, spasms, tingling and numbness
Describe the histology of osteomalacia.
No calcification of bone
More uncalcified osteoid
Bones are very bendy and cannot carry musculature very easily
What are the clinical consequences of osteomalacia?
- Sequelae
- Bone pain/tenderness
- Fracture (horizontal fractures at Looser’s zone at the neck of the femur are commonly seen)
- Proximal weakness
- Bone deformity e.g rickets
What is used to investigate mineralisation?
Fluorescent tetracycline labelling
- can be used to asses the advance of bone growth over a period
- care in giving to children as teeth turn black
What are the consequences of hyperparathyroidism?
- Hypercalcaemia (increased Ca2+ reabsorption)
- Hypophosphataemia (increased phosphate excretion in the urine)
- Osteitis fibrosa cystica (due to increased osteoclast activity)
- Increased Ca + PO4 excretion in urine
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 (85-90%)
2. Chief cell hyperplasia
State some causes of secondary hyperparathyroidism.
- Chronic renal insufficiency
2. 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
- Psychic Moans – psychosis and depression
What X-ray is of importance in showing the earliest skeletal change sin hyperparathyroidism?
X-ray of the hand
Subperiosteal bone erosions
What are the five features of renal osteodystrophy?
- Increased bone resorption (osteitis fibrosa cystica)
- Osteomalacia
- Osteoporosis
- Osteosclerosis
- Growth retardation
What are the consequences of renal osteodystrophy?
- Hyperphosphataemia
- Hypocalcaemia as a result of a decrease in vitamin D metabolism
- Secondary hyperparathyroidism (low calcium due to low Vis D so reflex hyperparathyroidism)
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 - rapid breakdown of bone
- Osteolytic-osteosclerotic - bone formation
- Quiescent osteosclerotic - quiescent stage
Describe the histology of Paget’s disease.
Prominent reversal lines
Masses of osteoclasts in the same site as osteoblasts
In which ethnicities is Paget’s disease rare?
Asian
African
(more common in caucasians, onset 40 years plus)
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
What are Howship’s Lacunae?
Pits in the bone surface where osteoclasts are found (also called resorption bays)
Where is RANK found?
Receptor activator for nuclear factor Kappa B
- found on osteoclast precursors in response to stimulation via M-CSF
Describe the aetiology of Paget’s
mainly unknown
- Familial cases show autosomal pattern of inheritance with incomplete penetrance (mutations in SQSTM1 or RANK)
- Parvomyxovirus type particles have been seen on EM in Pagetic bone – some doubt this is cause.
- Overuse or previous bone injury (pool player w finger he rested on table)
