Physiology of bone repair Flashcards
Imbalance towards bone resorption
Osteoporosis
Osteopenia
Rickets
Imbalance towards to bone formation
Osteopetrosis
Classifications of bone structure
Long bone
Flat bone
Macroscopic
- cortical bone
- cancellous
Microscopic
- lamellar
- woven
Lamellar bone
Secondary bone created by remodelling woven bone
Organised and stress oriented
Stronger and less flexible than woven bone
Woven bone
Collagen is randomly directed and the bone is not stress oriented
More osteocytes per unit volume, higher rate of turnover, weaker and more flexible than lamellar bone
Cancellous bone
Boney struts organised into a loose network with blood/ marrow between struts
Approximately 200 micrometers in diameter
30-90% of cancellous bone is porous and contains bone marrow
Increased porosity in osteoporosis
Cortical bone
Thick bone organised in osteons
Usually associated with or connected to the outer surface of the bone
Composition of bone
Osteoclasts
Osteocytes
Osteoblasts
Extracellular matrix
Osteoblasts
Formation of new bone and release of signalling substances
Produce protein component of acellular matrix to regulate bone growth and degradation
20-25 microns, round and regular in shape, mononucleate
Located on developing bone surfaces
Osteocytes
Quiescent mature cells embedded in bone matrix
For maintenance and detection of environmental and ageing stresses
Long and thin with extensive branches
The main cell body inside the lacuna
Osteoclasts
Giant multinucleate cells responsible for bone degradation and remodelling
Located in Howship’s lacunae at sites of bone resorption
Shape is regular, cube like, often with ruffled border
Ground substances
Substance surrounding the cells
Similar to extracellular matrix
This is the hard calcium phosphate
Haversian canal
Longitudinal canal within the bone tissue
Typically run parallel to the surface and along the long axis of the bone
The canals are surrounded by lamellae and all together thay are called a Haversian system or an osteon
A Haversian canal generally contains one or two capillaries and nerve fibres
Canaliculi
Microscopic canals between the lacuanae of ossified bone
The radiating processes of the osteocytes project into these canals
Osteocytes do not entirely fill up the canaliculi
Osteocytes arise from osteoblasts
From mesenchyme
- from precursor cells in bone marrow stroma
Osteoblasts are post-mitotic
- most osteoblasts will undergo apoptosis
- number of osteoblasts decreases with age
A low % of osteoblasts will become osteocytes locked in lacuna
Mesenchyme
A loosely organised, mainly mesodermal embryonic tissue which develops into connective and skeletal tissues, including blood and lymph
Composed mainly of ground substance with few cells or fibres
Osteoclast precursor
Same as monocytes
Phagocytose (bone matrix and crystals)
Secrete acids
Secrete proteolytic enzymes from lysosomes
Ruffled border
Specialised part of osteoclast where bone resorption occurs
Bone constituents
Extracellular matrix is 70% minerals
Plus abundant proteins and sparse cells
High compressive strength and tensile strength
A cellular elements of bone
- collagen fibres: protein, flexible but strong
- hydroxyapatite: mineral, provides rigidity
- calcium/ phosphate crystals
Glycosaminoglycans
Long polysaccharides
Highly negative
Attract water
Repel each other
Resists compression
Abundant in cartilage
Growth factors
Suspended in matrix
Revealed by osteoclast action
Leads to proliferation and mineralisation
Bone formation
Bone forms either as compact or cancellous and by either intramembranous or endochondral bone formation
Endochondral ossification
Bone formation based on cartilage model
Chondrocytes proliferate and secrete extracellular matrix and proteoglycans
Osteoblasts arrive and tehn osteoid is laid down and mineralisation begins
Precise modelling of the final bone is done by osteoclasts
Intramembranous ossification
Bone formation without a cartilage model
Osteoblasts lay down osteoid and begin mineralisation, forming tiny bony spicules
Nearby spicules join together into trabeculae
Factors governing remodelling
Recurrent mechanical stress
Calcium homeostasis
- plasma calcium is essential in maintaining structural integrity of skeleton
Mechanical stress- strengthens bone
Inhibits bone resorption and promotes deposition
Without weight bearing bone rapidly weakens
Surface osteoblasts and osteocyte network detect stresses
Skeleton reflects forces acting on it
Bisphosphates
For osteoporosis
- e.g. alendronate
Inhibit osteoclast mediated bone resorption
Related to inorganic pyrophosphate
- the endogenous regulator of bone turnover
- accumulate on bone and ingested by osteoclasts
Other drugs for osteoporosis
Encourage osteoblast formation of bone
- teriparatide
- portion of human parathyroid hormone
- intermittent application activates osteoblasts more than osteoclasts
Prevent osteoclast maturation
- denosumab
- monoclonal antibody that targets RANKL
Osteoporosis molecular mechanism
Osteoclasts cannot remodel bone
Defective vacuolar proton pump or
Defective chloride channel
Excess bone growth from osteoporosis
Bone growths at foramina press on nerves
Brittle (dense) bones
Blindness
Deafness
Severe anaemia
Fracture healing: reactive phase: haematoma and inflammation
Blood cells enter wound
Haematoma forms
Inflammatory cells invade
Granulation tissue formed
Aggregation of blood vessels
Fibroblasts
Bone precursor cells arrive from periosteum
Phase of fracture healing: soft callus formation
Woven bone (or hyaline cartilage) join the pieces
Woven bone near BVs
Fibrocartilage further away
Phase of fracture healing: hard callus formation
Lamellar bone replaces woven bone
Phase of fracture healing: remodelling
Trabecular bone replaces lamellar bone
Original bone shape
Compact bone formed where appropriate
Hormones of calcium regulation
PTH
- parathyroid chief cells
- increases plasma Ca2+
Vitamin D: 1,25-di-OH cholecalciferol
- made in stages: skin -> liver -> kidney
- increases plasma Ca2+
Calcitonin
- made by thyroid C cells
- tones down blood calcium
- calcium goes into bone
Vitamin D: production and activation
Skin: cholecalciferol (Vit D3) -> 25-OH cholecalciferol -> (kidney) 1,25-di-OH cholecalciferol -> Increase calbindin in gut enterocytes -> Increase in intestinal absorption of Ca2+ -> Increase Ca2+ reabsorption in kidneys -> Plasma Ca2+
Effects of vitamin D
Increases intestinal Ca2+ absorption
- increases calbindin
Stimulates kidneys to reabsorb calcium
Stimulates osteoclasts indirectly
- via osteoblasts
- comparatively weak effect
Vitamin D facilitates bone remodelling and thus increases serum Ca2+
Causes of low plasma calcium
Loss
- pregnancy
- lactation
- kidney dysfunction
Low intake
- insufficient ingestion of calcium
- rickets (low vit D)
Parathyroid dysfunction (surgery)
Chronic hypocalcaemia results in
Skeletal deformities
Increased tendency toward bone fractures
Impaired growth
Short stature (adults less than 5 feet tall)
Dental deformities
Acute hypocalcaemia leads to
Bleeding Anaesthesia Dysphagia Convulsions Arrhythmias Tetany Spasms and stridor
Low plasma calcium
Leads to excitability
Effects seem paradoxical
Makes membrane more excitable and less stable
Hypercalcaemia signs and symptoms
Can be asymptomatic
Reduced excitability
- constipation
- depression and other psychiatric
Abnormal heart rhythms
- short QT interval, ST segment gone
- widened T wave
Severe hypercalcaemia
- coma
- cardiac arrest
