Metabolic bone disease overview and histopathology Flashcards
What is the definition of metabolic bone disease?
A group of diseases that cause a decrease in bone density and strength, either by increasing bone resorption or decreasing bone formation
What are the main metabolic bone diseases?
Primary hyperparathyroidism Rickets/osteomalacia Osteoporosis Paget's disease Renal osteodystrophy
What are the symptoms of metabolic bone disease? (metabolic and bone)
Metabolic- Hypo/hypercalcaemia- hypo causes pins and needles, seizures and cardiac conduction problems Hypo/hyperphosphataemia Bone- Low phosphate - renal damage High phosphate - precipitation with calcium to form calcium phosphate, causing widespread tissue damage including atherosclerosis Pain Deformity Fractures
What is calcium mainly stored as in bone?
Inorganic hydroxyapatite
What type of bone is very metabolically active?
Cancellous (particularly in the vertebrae)
What is the continuous remodelling of bone?
Bone is resorbed and replaced 5% at any time
What does the continuous remodelling require?
Continuous exchange of ECF with bone fluid reserve
In regards to clinical medicine, what is the main concern with bone?
Tendency to fracture
What two aspects of bone are important in terms of bone strength and therefore possible fracture risk?
Quantity- Cortical thickness, mineral density, size
Quality- Architecture, bone turnover (low- no mending and high- too fragile), cortical porosity (holes mnade during remodelling are weak), trabecular connectivity (connections within cancellous bone)
How is the tibia modelled during growth?
Bone is added, more in the anterior/posterior direction due to the stresses put on the tibia bone during walking- modelling occurs at areas of higher stress
How do you assess bone structure and function? (4)
Bone histology
Biochemical tests
Bone mineral densitometry e.g. in osteoporosis
Radiology e.g. osteomalacia
What is the function of bone? (3)
Mechanical- support and site for muscle attachment allowing movement and strength
Protective- vital organs, bone marrow
Metabolic- main reserve of calcium, allowing release and storage of calcium
What is the difference between bone and all other organs?
It is naturally mineralised
What is bone naturally comprised of?
Inorganic calcium hydroxyapatite (65%) Organic (35%): - Collagen matrix (type 1 mainly) - Water - Non-collagenous protein and carbohydrate
What is calcium hydroxyapatite?
Inorganic salt formed by calcium and phosphate which acts as a storehouse for 99% of the Ca in the body, 85% of phosphate and 65% Na and Mg
What are the two parts of a bone?
Diaphysis (long shaft)
Epiphysis (head of bone)
What is a facet joint?
Small articular surfaces at synovial joints that enable bone to act as a lever in joints
What does articular cartilage do?
Provide a frictionless surface
What does periosteum do?
Surrounds bone, providing a protective covering as well as pathways for blood vessels to enter the bone itself
What are condyles?
Knuckle shaped prominence at the end of the bone
What is the cortex of the bone like and what does it do?
It is thick and strong and is the part of the bone to which muscles attach
What is the medulla of the bone like and what occurs in the medulla?
Soft trabecular/cancellous bone where most metabolism occurs
Where are cortical bones found?
They are usually long and form 80% of the human skeleton (appendicular)
Where are cancellous/trabecular bones found?
Forms 20% of human skeleton (axial)- especially present in vertebrae and pelvis
What are the indications for use of bone biopsy?
Investigating an abnormality seen on x-ray
Evaluate bone pain or tenderness
Bone tumour diagnosis
Determining the cause of unexplained infection
Evaluating the progress of therapy
What are the two types of bone biopsy and when are they both used?
Closed (Jamshidi needle core biopsy in the iliac crest)- used most commonly as less risk
Open- for sclerotic or inaccessible lesions
What is cartilage?
Load bearing tissue composed predominantly of type 2 collagen and a variable amount of elastic fibres
Where is elastic cartilage found?
Ears, nose, epiglottis and larynx
Where is hyaline cartilage found and what is it effective at?
It is present on the ends of long bones and is very effective as a shock absorber and resists large compressive forces generated by weight transmission
What are osteoblasts?
Bone cells that build bone by laying down osteoid (uncalcified)
What are osteoclasts?
Multinuclear bone cells of the macrophage family which resorb or chew bone
What are osteocytes?
Osteoblast-like cells which sit in lacunae in bone
What do osteocytes do after microdamage to bone, following mechanical stress, exposure to some cytokines or at random?
Secrete messages to the surface cells (stromal)
What do stromal cells do once activated by messages from osteocytes?
Produce M-CSF (macrophage colony stimulating factor)- this causes differentiation of cells into pre-osteoclasts
Divide to produce pre-osteoblasts
What do pre-osteoclasts have?
Membrane receptors called RANK (receptor activator for nuclear factor kB)
What do pre-osteoblasts express?
RANK ligand
What happens when RANK-L binds to RANK?
Cells fuse and differentiate into mature multinucleated osteoclasts thus increasing bone resorption
At the same time as Rank-L binding to RANK, what do mature osteoblasts make?
Free floating OPG (osteoprotegrin)
What can OPG do?
It can bind to RANK-L allowing osteoblast activity to dominate -> increased bone build up
Anatomically, what are the three types of bone?
Flat- scapula
Long- limbs
Cuboidal- vertebral
What leads to flat bones?
Intramembranous ossification
What leads to the development of long bones?
Endochondrial ossification
Apart from anatomically, how else can bones be classified?
Their development:
Immature/woven
Mature/lamellar
What is immature/woven bone like?
Lamellae are absent
Collagen fibres are disorganised; such as in states of high bone turnover (Paget’s, tumours) where they are in random bundles that are not closely packed
Where is the only place in an adult that woven bone should be found?
Base of the tooth
When is lamellar bone particularly evident?
When viewed under polarised light- collagen fibres are arranged in alternating orientations allowing for highest density
What is metabolic bone disease caused by?
Disordered bone turnover due to imbalance of various chemicals in the body
What is the overall effect of metabolic bone disease?
Reduced bone mass (osteopenia) leading to increased risk of fracture
How is metabolic bone disease assessed?
Using histomorphology which requires un-decalcified bone
What are the categories of metabolic bone disease?
Endocrine related- Vit D, PTH
Non-endocrine related- Age, iatrogenic
Disuse osteopenia
What are the primary causes of osteoporosis?
Age
Post-menopausal
What are secondary causes of osteoporosis?
Drugs and systemic disease
What is the histopathology of a bone of someone with osteoporosis like?
Many holes and cysts
Mineralisation is normal but large marrow spaces
What is very common with osteoporosis?
Neck and femur fractures
What is osteomalacia?
Condition of defective bone mineralisation
What can osteomalacia be caused by?
Vit D deficiency
Deficiency of phosphate usually related to chronic renal disease
What is the mechanism of osteomalacia?
Vit D deficiency causes increase in PTH and subsequent increased bone resorption= hyperparathyroidism
Also causes hypocalcaemia
What is the histology of a bone of someone with osteomalacia like?
No calcification of bone - more uncalcified osteoid (stains orange instead of green)- bones are very bendy so can’t carry musculature easily
What are the sequelae (consequences) of osteomalacia?
Bending Bone pain Fracture Proximal weakness Bone deformity
How can you investigate bone mineralisation?
Tetracycline fluorescent labelling which looks at mineralisation rate- Problems show fuzzy outline as opposed to distinct
What does the excess PTH in hyperparathyroidism lead to?
Increased osteoclast activity > Increased bone resorption- osteitis fibrosis cystica
Increased calcium reabsorption and increased phosphate excretion- hypercalcaemia and hypophosphataemia
Increased absorption of dietary calcium via calcitriol production
Which 4 organs are affected by hyperparathyroidism?
PT glands
Bone
Kidneys
Proximal small intestine
What causes primary hyperparathyroidism?
PTH adenoma
Chief cell hyperplasia
What causes secondary hyperparathyroidism?
Chronic renal disease
Vit D deficiency
What are the symptoms of hyperparathyroidism?
Stones (kidney)
Bones (osteitis fibrosa cystica and bone resorption)
Abdominal groans (acute pancreatitis)
Psychic moans (psychosis and depression)
What is the most important investigation for hyperparathyroidism?
XRAY of the hand
What does an XRAY of the hand show in someone with hyperparathyroidism?
Sub-periosteal bone erosions
Small areas of resorption in the long bones of the fingers filled with osteoclasts- brown cell tumours
What skeletal changes does renal osteodystrophy/chronic renal disease comprise?
Osteitis fibrosis cystica (increased bone resorption) Osteomalacia Osteosclerosis Growth retardation Osteoporosis
What are the symptoms of renal osteodystrophy?
Hyperphosphataemia Hypocalcaemia resulting from decreased Vit D synthesis Secondary hyperparathyroidism Metabolic acidosis Aluminium deposition
What is Paget’s disease?
Disorder of bone turnover due to lack of communication between cells
What are the 3 stages of Paget’s?
Osteolytic whereby osteoclasts predominate -> bone resorption
Osteolytic-osteosclerotic- blasts fight back
Quiescent- osteosclerotic
What is the epidemiology of Paget’s disease?
Middle aged
Common but rare in Asians and Africans
Where is Paget’s normally found in the body?
Skull Sternum Spine Humerus Pelvis Femur Tibia
What are the clinical symptoms of Paget’s?
Pain Microfractures Nerve compression Skull changes Deafness Haemodynamic changes Cardiac failure Hypercalcaemia Development of sarcoma in area of involvement
What is a haversian canal?
Channel that the blood vessels run in the bone
What are caniculae important for?
They are routes for cell communication
What are Howship’s lacunae?
Pits in the bone surface in which osteoclasts are found often called resorption bays
