Metabolic Bone Disease – Histopathology Flashcards by Georgia Leggett

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

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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

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Describe the classification of bone as cortical

Long bones

80% of skeleton

Appendicular skeleton

80-90% calcified

Mainly structural, mechanical + protective role

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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

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What are the 2 types of bone biopsy?

Closed: (Jamshidi) needle inserted into biopsy site

Open: for sclerotic or inaccessible lesions

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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

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

M-CSF (produced by osteoblasts)

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Which cells produce RANKL and what is its effect?

Pre-osteoblasts

It stimulates the maturation of osteoclasts

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

Osteoprotegrin (decoy receptor for RANKL)

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How are bones classified anatomically?

Flat: Skull

Long: Femur

Short: Carpals

Irregular: Pelvis

Sesamoid: Patella

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What type of ossification leads to the formation of: a. Long Bones b. Flat Bones

Long bones = Endochondral ossification

Flat bones = Intramembranous ossification

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How else can bone be classified?

Macroscopically: Trabecular (cancellous/spongey) or compact (cortical)

Microscopically: Woven (immature) or lamellar (mature)

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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

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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

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Describe the staining of mineralised and unmineralised bone

Mineralised: green

Unmineralised: orange

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What are the primary and secondary causes of osteoporosis?

Primary: Age, Post-menopause

Secondary: Drugs, Systemic disease

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What is osteoporosis?

BMD T-score of -2.5 or lower SDs different from mean peak BMD

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Describe the histology of osteoporotic bone.

Thinner, less interconnected trabeculae

Some trabeculae are free floating

Holes + cysts

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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)

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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

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Describe the histology of osteomalacia.

No mineralisation of bone

More unmineralised osteoid

Bones are very bendy + cannot carry musculature easily

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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

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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

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Cortical bone

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Cartilage

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Cancellous bone

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Epiphyseal line

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Medullary cavity

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