Metabolic bone disease: Histopathology Flashcards
Give 4 functions of bone
Structural
Mechanical
Protective
Metabolic
Describe the composition of bone
65% inorganic - Calcium hydroxyapatite
(Stores 99% of body calcium, 85% of phosphorus, 65% sodium)
35% organic
What are the main anatomical regions of the bone
Diaphysis - Medulla, cortex, periosteum
Metaphysis - joins diaphysis to epiphysis (epiphyseal line where growth plate would have been during growth)
Epiphysis - Articular cartilages, chondyles
What % of bone must be mineralised to show up on X-ray?
50%
What are the bone types/classifications?
Anatomical bones - flat, long, short, irregular, sesamoid
Macroscopic structure - cancellous/cortical/spongy bone, trabeculae
Microscopic structure - Woven bone (immature), Lamellar bone (mature)
What are cortical bones?
Long bones 80% of skeleton Appendicular Long turnover, 80-90% calcified Mainly structural/mechanical/protective
What are cancellous bones?
Vertebrae + pelvis 20% of skeleton Axial Fast turnover, 15-25% calcified Mainly METABOLIC Large SA
What are the different bone cells?
Osteoclasts - multinuclear, resorb bone
Osteoblasts - thin cuboid shape, produce osteoid to form new bone
Osteocytes - mechanosensory network embedded in mature bone
Osteoblasts can become embedded in bone to become osteocytes
Describe bone remodelling cycle
Osteocyte apoptosis -> release of RANKL
RANKL binds to RANK on osteoclast precursor, forming mature osteoclast -> bone resorption
When osteoclasts die they are replaced by Reversal cells which trigger the formation of mature osteoblasts -> bone formation
Osteoblasts also regulate formation of osteoclasts
Why would you perform bone biopsy?
Confirm diagnosis Find cause of bone pain/tenderness Investigate abnormality seen on x-ray Bone tumour diagnosis (benign vs malignant) Evaluate therapy performance
Types of bone biopsy?
Closed (common) - core biopsy using needle
Open - for sclerotic (very hard) bone or inaccessible lesions
What type of biopsy would be used to determine condition of whole skeleton or to monitor treatment?
Transiliac bone biopsy
Core consisting of cortical bone on either end AND cancellous/trabecullar bone in the middle
What histological stains do you use for bone biopsy?
H&E staining - basic
Masson - Goldner Trichrome staining: can distinguish mineralised (green) and unmineralised bone (orange)
Tetracycline/Calcein labelling: Fluorescent labelling of newly forming bone, GOLD STANDARD for assessing bone turnover)
What is metabolic bone disease?
Reduced bone mass/strength
Due to imbalance of chemicals in the body
This causes altered bone cell activity, rate of mineralisation or changes in bone structure
List common metabolic bone diseases
Osteoporosis Osteomalacia/Rickets Primary hyperparathyroidism Renal osteodystrophy Paget's disease
Mechanism and causes of osteoporosis?
Bone mineral density T-score of -2.5 or lower
PRIMARY = age, menopause
SECONDARY = drugs, systemic disease
Rapid turnover of trabecullar bone (which is highly metabolic)
How would osteoporosis look under Masson-Goldner trichrome staining?
Less/thinner trabecullar bone (less green)
Comparatively more unmineralised osteoid (more orange)
Mechanism and causes of osteomalacia? What are the types?
Defect in mineralisation of normally synthesised bone matrix
In children = RICKETS
Two types: Vit. D deficiency OR phosphate deficiency
How does Vit D deficiency cause osteoporosis?
Less Calcium absorption/reabsorption
How would osteomalacia look under trichrome staining?
LOTS of orange (unmineralised osteoid due to lack of calcium)
Hardly any green (mineralised bone)
Clinical features of osteomalacia?
Bone/pain Fracture Proximal weakness Bone deformity Looser's zone fracture at areas of high tensile stress (occurs at right angle to cortex)
Mechanism and causes of hyperparathyroidism?
Excess PTH leading to increase calcium reabsorption + phosphate excretion in urine (hypercalcaemia + hypophosphatemia)
PTH indirectly stimulates osteoclast activity (by binding to osteoblasts and increasing RANKL)
This leads to increased bone resorption -> release of Ca (hypercalcaemia)
Results in osteitis fibrosa cystica
Primary hyperparathyroidism: parathyroid adenoma
Secondary hyperparathyroidism: chronic renal deficiency, vitamin D deficiency
Which organs are affected by PTH and how do they control calcium metabolism?
Parathyroid glands (release PTH)
Bones (PTH -> release of Ca)
Kidneys (absorption of Ca)
Proximal Small Intestine (reabsorption of Ca)
Histology of hyperparathyroidism?
You would be able to see sub-periosteal bone erosions as a result of osteitis fibrosa cystica
Also see tunnelling erosions where center of trabecullae are eroded
May also see Brown cell tumours, where bone has been replaced by fibrous tissue
What is renal osteodystrophy?
Chronic renal disease resulting in skeletal changes:
Increased bone resorption (OFC) Osteomalacia Osteosclerosis Growth retardation Osteoporosis
What is Paget’s disease? What are the 3 stages?
Disorder of bone turnover
- Osteolytic phase - rapid breakdown of bone
- Mixed phase - osteoblasts + osteoclasts
- Osteosclerotic phase - osteoblasts form disorganised mosaic-patterned bone
Aetiology unknown
Clinical symptoms of Paget’s disease?
Often asymptomatic Pain Microfractures Nerve compression Deafness
Histology of Paget’s disease?
Thickening of cortex (sclerosis)
Cavity in middle of bone (osteolytic black spots)
Mix of osteoblasts/osteoclasts forming/resorbing bone
Mosaic pattern - disorganised bone structure
