Metabolic Bone Disease – Histopathology Flashcards
What are the 4 main functions of bones?
Structure: give structure + shape to the body
Mechanical: site for muscle attachment
Protective: vital organs + bone marrow
Metabolic: reserve of calcium + other minerals
What are the 2 main components of bone and what are their relative proportions?
Inorganic (65%): calcium hydroxyapatite (store of 99% of the body’s Ca, 85% of phosphorous)
Organic (35%): bone cells + protein matrix
Describe the classification of bone as cortical
Long bones
80% of skeleton
Appendicular skeleton
80-90% calcified
Mainly structural, mechanical + protective role
What are the indications for bone biopsy?
Evaluate bone pain or tenderness
Investigate abnormality seen on X-ray
For bone tumour diagnosis
To determine cause of unexplained infection
To evaluate therapy
What are the 2 types of bone biopsy?
Closed: (Jamshidi) needle inserted into biopsy site
Open: for sclerotic or inaccessible lesions
What are the 3 types of bone cell?
Osteoblasts: mononuclear cells, produce osteoid to form new bone
Osteoclasts: multinucleate cells, resorb bone
Osteocyte: mechanosensory network embedded in mature bone
What cytokine is important for stimulating the differentiation of osteoclast precursors into pre-osteoclasts?
M-CSF (produced by osteoblasts)
Which cells produce RANKL 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 (decoy receptor for RANKL)
How are bones classified anatomically?
Flat: Skull
Long: Femur
Short: Carpals
Irregular: Pelvis
Sesamoid: Patella
What type of ossification leads to the formation of: a. Long Bones b. Flat Bones
Long bones = Endochondral ossification
Flat bones = Intramembranous ossification
How else can bone be classified?
Macroscopically: Trabecular (cancellous/spongey) or compact (cortical)
Microscopically: Woven (immature) or lamellar (mature)
What is metabolic bone disease?
Reduced bone mass + strength due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc.)
Causes altered bone cell activity, rate of mineralisation or changes in bone structure
What are the 3 main categories of metabolic bone disease?
Related to endocrine abnormality (e.g. Vit D + PTH)
Non-endocrine (e.g. age-related osteoporosis)
Disuse osteopaenia
Describe the staining of mineralised and unmineralised bone
Mineralised: green
Unmineralised: orange
What are the primary and secondary causes of osteoporosis?
Primary: Age, Post-menopause
Secondary: Drugs, Systemic disease
What is osteoporosis?
BMD T-score of -2.5 or lower SDs different from mean peak BMD
Describe the histology of osteoporotic bone.
Thinner, less interconnected trabeculae
Some trabeculae are free floating
Holes + cysts
What is osteomalacia and what can it be caused by?
Defective bone mineralisation of normally synthesised bone matrix
Can be caused by:
Vitamin D deficiency
Phosphate deficiency (usually related to CKD)
What are the metabolic and endocrine consequences of vitamin D deficiency?
Secondary hyperparathyroidism –> increased bone resorption
Hypocalcaemia: neuronal excitability causing muscle twitching, spasms, tingling + numbness
Describe the histology of osteomalacia.
No mineralisation of bone
More unmineralised osteoid
Bones are very bendy + cannot carry musculature easily
What are the clinical consequences of osteomalacia?
Bone pain/tenderness
Fracture (horizontal fractures at Looser’s zone at neck of femur are common)
Proximal weakness
Bone deformity
What is used to investigate mineralisation?
Masson-Goldner Trichrome staining
What are the consequences of hyperparathyroidism?
Increased Ca2+ + PO4 excretion in urine
Hypercalcaemia (increased Ca2+ reabsorption)
Hypophosphataemia (increased phosphate excretion in urine)
Osteitis fibrosa cystica (due to increased osteoclast activity)
List the 4 organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.
Parathyroid glands
Bones
Kidneys
Proximal small intestine
State 2 causes of primary hyperparathyroidism.
Parathyroid adenoma
Chief cell hyperplasia
State 2 causes of secondary hyperparathyroidism.
Chronic renal deficiency
Vitamin D deficiency
List 4 symptoms of hyperparathyroidism?
Stones: calcium oxalate renal stones
Bones: osteitis fibrosa cystica
Abdominal Groans: acute pancreatitis
Psychic Moans: psychosis + depression
What is the most important investigation for hyperparathyroidism and what will it show in someone with hyperparathyroidism?
X-ray of the hand
Subperiosteal bone erosions
Brown cell tumours
What are the 5 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
Metabolic acidosis
Aluminium deposition
What is Paget’s disease?
Disorder of bone turnover (there is a lack of proper communication between the cells)
What are the 3 stages of Paget’s disease?
Osteolytic (focal bone loss)
Osteolytic-osteosclerotic (osteoblasts respond to increased resorption)
Quiescent osteosclerotic (results in disorganised lamellae in mosaic pattern)
Describe the histology of Paget’s disease.
Prominent reversal lines
Masses of osteoclasts in the same site as osteoblasts
Coarse, disorganised trabeculae
Thickened cortices
Describe epidemiology of Paget’s disease
Onset >40
M > F
Rare in Asian/ African
Majority polyostic
Which sites does Paget’s disease most commonly affect?
Skull
Sternum
Spine
Humerus
Pelvis
Femur
Tibia
List 9 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 (AKA. resorption bays)
Describe the classification of bone as cancellous.
Vertebrae + pelvis
20% of skeleton
Axial
15-25% calcified
Mainly metabolic
Large SA
What is the function of the osteocyte canalicular network formed by dendritic process between osteocytes?
Mechanosensory function
Allows bone to signal location that requires repairing or removing
Describe the micro anatomy of cortical bone
Organised in parallel columns composed of lamellae (concentric rings of bone surrounding a central channel).
Lamellae form when osteocytes lay bone matrix + entrap themselves in lacunae spaces
What is the circumferential lamellae surrounding the whole bone shaft?
Periosteum
Describe the micro anatomy of cancellous bone
Anastomosing strips of slender bone (trabeculae) enclose marrow + blood vessels.
Where would you find immature bone?
Developing skeleton
Sites of rapid growth
Sites of pathological bone turnover
Describe the bone remodelling cycle
Osteocytes apoptose, releasing RANKL which signals for osteoclasts to form at that site
Osteoclasts resorb old/ damaged bone
Osteoclasts die away
Osteoblasts produce osteoid to replace the bone that’s been removed
How could you differentiate between the bone cells histologically?
Osteoblasts= mononuclear, cuboidal, flat, on surface
Osteoclasts= multinucleate
Osteocytes= embedded in lacunae
What is used to investigate dynamic rate of bone turnover? How?
Tetracycline/ Calcein labelling
Inject on 2 separate occasions, measure distance between 2 lines formed
What are the 3 different types of osteoporosis?
High turnover: increased resorption (more so than formation)
Low turnover: decreased formation (more decreased than resorption)
Increased resorption + decreased formation
Label the diagram
Cortical bone
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Cartilage
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Cancellous bone
Label the diagram
Epiphyseal line
Label the diagram
Medullary cavity
Label the diagram
Marrow
