Metabolic Bone Disease - Histopathology (13.01.2020) Flashcards
Osteomalacia
Defective mineralisation of normally synthesized bone matrix
• Rickets in children
• Effectively 2 types
– Deficiency of vitamin D – Deficiency of PO4
Ricktes
- vitamin D deficiency in children
- bowing of the legs
- widening of growth plates
- bone try to compensate undermineralisation by deforming
Looser’s zone
- areas of high tensile stress
- horizontal fractures (occur in osteomalacia)
- 90 degrees to the bone
Hyperparathyroidism
- excess PTH
- increased phosphate excretion in bone
- hypercalcaemia
- hypophosphatemia
- skeletal changes of osteitis fibrosa cystica
What are the organs directly or indirectly affected by PTH?
- PT-gland
- bones
- kidneys
- proximal SI
Primary hyperparathyroidism
- PT Adenoma (85-90%)
- chief cell hyperplaisa
Secondary hyperparathyroidism
- chronic renal deficiency
- vitamin D deficiency
What are the effects of hyperparathyroidism>
- Stones(Caoxalaterenalstones)
- Bones(osteitisfibrosacystica,boneresorption)
- Abdominalgroans(acutepancreatitis)
- Psychic moans (psychosis & depression)
=> unikely to see this unless undiagnosed for a number of years
Renal Osteodystrophy
Comprises all the skeletal changes resulting from chronic renal disease:
– Increased bone resorption (osteitis fibrosa cystica) – Osteomalacia (due to hypocalcaemia) – Osteosclerosis – Growth retardation – Osteoporosis
Paget’s disease satges
- Osteolytic (focal bone loss)
- Osteolytic-osteosclerotic (osteoblasts respond)
- Quiescent osteosclerotic (osteoblasts react and both cell types burn out and end up with disorganised bone)
Paget’s disease - epidemiology
- Onset > 40y (affects 3-8% Caucasians > 55y)
- M>F
- Rare in Asians and Africans
- Mono-ostotic 15% (only affects one bone)
- Remainder polyostotic
- genetic aspect, but ethology is not yet known
Paget’s disease
- Onset > 40y (affects 3-8% Caucasians > 55y) M>F
- Rare in Asians and Africans
- Mono-ostotic 15% (only affects one bone)
- Remainder polyostotic
- genetic aspect, but ethology is not yet known
- may also be of overuse of bones and previous bone injury
Clinical symptoms of Paget’s disease
– pain
– microfractures
– nerve compression (incl. Spinal N and cord)
– skull changes may put medulla at risk
– deafness
– +/- haemodynamic changes, cardiac failure
– hypercalcaemia
– Development of sarcoma in area of involvement 1%
What are the functions of bone?
• STRUCTURE – give structure and shape to the body • MECHANICAL – sites for muscle attachment • PROTECTIVE – vital organs and bone marrow • METABOLIC – reserve of calcium and other minerals
Composition of bone
• INORGANIC - 65%
– calcium hydroxyapatite (Ca10(PO4)6(OH)2)
– is storehouse for 99% of Calcium in the body
– 85% of the Phosphorus, 65% Sodium, Magnesium
• ORGANIC - 35%
– bone cells and protein matrix
What are the different bone types? In what ways can bones be classified?
• Anatomical bones
– Flat,long,short/cuboid,irregular,sesamoid
• Macroscopic structure
– trabecular/cancellous/spongy
– cortical/compact
• Microscopic structure
– Woven bone (immature) – Lamellar bone (mature)
Cortical vs. cancellous bone
- CORTICAL
- long bones
- 80% of skeleton
- appendicular
- 80-90% calcified
- mainly structural, mechanical, and protective
- CANCELLOUS
- vertebrae & pelvis
- 20% of skeleton
- axial
- 15-25% calcified
- mainly metabolic
- large surface area
How can you differentiate lamellar and woven bone?
- woven bone is immature and unstructured (it is the initial bone that is layer down before it is replaced by mature bone. Also found where there is rapid growth or pathological high turnover; weak compared to mature bone -> can cause difficulties.
- lamellar bone is mature and forms concentric circles
What are the different types of bone cells?
- Osteoclasts - multinuclear cells that resorb/remove bone
- Osteoblasts - produce osteoid to form new bone
- Osteocytes - mechanosensory network embedded in mature bone
What is osteoid?
- the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins.
- composed of type 1 collagen as well as glycosaminoglycan
What fraction of bone has to be mineralised to be seen on an XR?
about 50%
Periosteal reaction
A periosteal reaction is the formation of new bone in response to injury or other stimuli of the periosteum surrounding the bone. It is most often identified on X-ray films of the bones.
How do osteoblasts control the number of osteoclasts being formed?
- release RANKL and M-CSF
- also release a decoy receptor for RANKL
What are the key osteoclastic factors? Which cells produce them?
- M-CSF and RANKL
- produced by osteoblasts
Describe the bone remodelling cycle
- osteoclastic bone resorption
AND
- osteoblastic bone formation
=> balanced by the interaction of the three bone cell types
What are the phases of the bone remodelling cycle?
- Activation (osteocytes sense new stresses and remodelling is needed to account for these stresses. They send signals to osteoclasts to come to the site by apoptosing and releasing RANKL)
- Osteoclastic bone resporption
- Reversal
- osteoblastic bone formation
- Quiescence
What are the reasons to perform a 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 types on bone biopsy?
- open - for sclerotic (osteosclerosis, bone thickening) / inaccessible lesions or if a larger sample is needed
- closed - needle - core biopsy (Jamshidi needle)
What tool is used for a closed bone biopsy?
Jamshedi needle
What is the Jamshedi needle used for?
CLOSED bone biopsy
Where can bone biopsies be performed?
- at any site
- but if the reason is general and not bone specific a typical one would be transiliac bone biopsy b/c you can see cortical bone, trabecular bone.
- type of bone you see depends on the location
Which histological stains can be used in bone marrow biopsies?
- H&E (
- Masson - Goldner Trichrome (mineralised vs. unmineralised bone)
- Tetracycline/Calcein labelling (dynamic, measure bone formation and turnover)
Masson - Goldner Trichrome
- mineralised bones is green
- unmineralised osteoid is orange
- particularly useful in patients with osteomalacia
Tetracycline/Calcein labelling
- incorporated into mineralising from of any osteoid being mineralised at that momebt
- inject it again another tiume
- you can see how much bone was mineralised in the timespan between the 2 injections by measuring the distance between the fluorescent lines.
What is metabolic bone disease?
- A group of diseases that cause reduced bone mass and reduced bone strength
- Due to imbalance of various chemicals in the body (vitamins, hormones, minerals, etc)
- Cause altered bone cell activity, rate of mineralisation, or changes in bone structure
Common metabolic bone diseases
- Osteoporosis
- Osteomalacia/Rickets
- Primary hyperparathyroidism
- Renal osteodystrophy
- Paget’s disease
Osteoporosis
• Defined as a bone mineral density T-score of -2.5 or lower – Standard deviations different from mean peak bone mass BMD
What are the types of osteoporosis?
- Primary (age, post-menopausal) vs. Secondary (drugs, disease)
- high turnover vs. low turnover (either way osteoclasts are more active than osteoblasts)
How does osteoporotic bone appear on a histological sample?
- fewer trabeculae
- thin trabeculae
- less interconnected
mainly impacts trabecular bone
How does bone in osteomalacia appear histologically?
- Masson-goldner trichome stain: lots of orange as the bone is not mineralised.
Sequelae of osteomalacia
- bone pain/tenderness
- fracture
- proximal weakness
- bone deformity
osteitis fibrosa cystica
- seen in HPT
- bone has been replaced by fibrous tissue
Histological features of HPT
- tunneling resorption (center of trabeculae removed, resorbed central channel)
- osteitis fibrosis cystica (fibrous tissue replaces bone; giant cell reparative granuloma, giant cells surrounded by fibrous tissue and reactive bone forming next to them.
- brown tumours
Brown cell tumour
- on XR: holes in the bone are brown tumor regions
Aetiology of Paget’s disease
- Aetiology is 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.
