Physiology of bone repair Flashcards
The bone must balance resorption and formation
What happens if either of these processes are imbalanced?
- Imbalance of resorption –> osteoporosis, osteopenia, rickets
- Imbalance of formation –> osteoporosis
How are bones classified?
- Long/flat?
- Macroscopic: cortical bone, cancellous (spongy) with spicules and trabeculae
- Microscopic: lamellar (osteons), woven (immature, disorganised)
What is the composition of bone and what are the their functions
LIVING CELLS
- Osteoblasts- sit on surface, produce protein component of matrix
- Osteoclasts- responsible for bone degradation and remodelling
- Osteocytes- quiscent cells embedded in bone matrix to maintain bone
EXTRACELLULAR MATRIX
- bone dominated by this (70%)
- Inorganic: minerals, abdundant proteins and few cells
Describe the structure of lamellae bone
At the centre is Haversian canal surrounded by lamellae. Surrounding this structure is osteocytes, with canaliculi forming projections from it. Theres is ground substance between cells
This describes an osteon
- cylindrical structures that contain a mineral matrix and living osteocytes connected by canaliculi, which transport blood. They are aligned parallel to the long axis of the bone. Each osteon consists of lamellae, which are layers of compact matrix that surround a central canal called the Haversian canal.
How do bone cells communicate?
- Communication system between cells immobilised in bone matrix
Describe the origin of osteoblasts and osteocytes
What happens to the number of osteoblasts with age?
- Osteocytes arise from osteoblasts
- from mesenchyme (from precursors in bone marrow stroma)
- Osteoblasts are post mitotic. Most will undergo apoptosis –> number decreases with age
- Low number of osteoblasts become osteocytes locked in lacuna
Describe osteoclasts according to the following parameters
- Cell structure and impact on functionality
- Origin
- Function
- Resorption site
- Multinucleare (40-100um, 15-20 closely packed oval shaped nuclei)
- Able to proliferate
- Haematopoietic stem cell (same as blood cells)
- Phagocytose bone matrix and crystals, secrete acids, secrete proteolytic enzymes from lysosomes
- Ruffled border= resorption site
How do the constituents of allow bone to have high compressive strength and tensile strength
- Collagen fibres (protein)- flexible but strong
- Hydroxyapatile (mineral)- provides rigidity
** Collagen act as rods and hydroxyapatile acts as cement in reinforced concrete
Describe glycosaminoglycans
- Long polysaccharides
- Highly negative
- Attract water
- Repel each other
- Resist compression
- Abundant in cartilage
Where are bone growth factors?
What is bone remodelling? What is the role of osteoblasts in this?
Use your answer to describe the cycle
Suspended in matrix revealed by osteoclast action leading to proliferation and mineralisation
Bone turnover - the activation-resorption-formation sequence
- Osteoblasts lay done bone but they also stimulate osteoclasts to break it
During resorption osteoclasts liberate matrix bound GF. Osteoprogenitor cells activated and osteoblasts lay down bone. Maintained on surface under influence of IL6, mechanical factors, hormones and other cytokines at rest
How does bone form?
As compact or cancellous bone by either intramembranous or endochondral bone formation
Describe the two factors that remodelling is governed by
- Recurrent mechanical stress
- Bone reflects forces acting on it so it strengthens bone, surface osteoblasts/cytes detect stress
- Inhibit bone resorption, promotes deposition
- Without weight bearing (space travel, bed rest) bone rapidly weakens - Calcium homeostasis
- Plasma calcium is essential in maintaing structural integrrity of skelton
BISPHOSPHATES
Indication:
MOA:
- Osteoporosis
- Inhibit osteoclast-mediated bone resorption
- Related to inorganic pyrosphosphate, the endogenous regulator of bone turnover. it accumulates on bones and is ingested by osteoclasts interfering with its metabolis
TRIPARATIDE
What does it do?
- Encourages osteoblast formation of bones
- Portion of PTH
- Intermittent application activates osteoblasts > osteoclasts
DENOSUMAB
Type of drug?
What does it do?
- Monoclonal anitbody that targets RANK ligand
- Prevents osteoclast maturation
Consider OSTEOPETROSIS
- Genetic penetrance
- MOA
- Clinical signs
- Autosomal recessive
- Osteoclasts cannot remodel bone, defective vacuolar proton pump or defective chloride channel
Outline the first stage of fracture healing
- Reactive phase: haematoma and inflammation
- blood cells enter wound forming haematoma
- inflammatory cells invade and granulation tissue formed
- aggregation of blood vessels, fibroblasts
- bone precursor cells arrive from periosteum
Outline stage 2-4 of fracture healing
- SOFT CALLUS FORMATION
- woven bone (or hyaline cartilage) join the pieces near blood vessels, fibrocartilage laid down further away from blood vessels - HARD CALLOUS FORMATION
- lamellar bone replaces woven bone - REMODELLING
- trabecular bone replaces (endochon)
lamellar bone
- original shape produced and compact bone formed where appropriate
How long does it take for a fracture to heal?
- Upper body: 2-3 weeks
- Lower body: >4 weeks
Consider the hormones of calcium regulation
How does PTH work and where is it produced?
- Produced by parathyroid chief cells
- Increases plasma concentration of calcium
PTH bnd the PTH receptor expressed by osteoBLASTS which causes upregulation of expression of RANK-L ligand on esteoblast.
Binding of osteoclast precursor to RANK L causes it differentiate and fuse (maturation) which results in bone resorption.
- Simultaneous OPG expression on osteoblast (decoy receptor
- The effects of intermittent PTH are not the same as continuous
Consider the hormones of calcium regulation
What is the chemical name for vitamin D?
Describe its synthesis
State its effects
1,25-di-OH cholecalciferol (Caltritriol)
Made in stages from skin to liver and kidney (or dietary)
Cholecalciferol (Vit D3) in skin converted to 25 OH cholecalciferol in liver. This is converted to 1,25-di-OH cholecalciferol in kidneys which increases calbindin in gut enterocytes.
The result in an increase in intestinal absorption of calcium and increased calcium reabsorption at the kidey
- It faciliates bones remodelling and increases serum [calcium].
- Stimulates osteoclasts indirectly via osteoblasts (weakly)
Consider the hormones of calcium regulation
Where is Calcitonin made?
Function?
Clinical use?
- Made by thyroid C cells
- Tones down blood calcium ( calcium goes into bone)
- Used as treatment for osteoporosis
What are the causes of hypocalcaemia
- PRODUCTION: Parathyroid dysfunction
- LOSS: kidney dysfucntion, lactation, pregnancy
- LOW INTAKE: rickets, insufficient ingection of calcium
Chronic hypocalcaemia results in:
List 5
- Dental deformities
- Short stature (adults <5ft)
- Impaired growth
- Increased tendency of fractures
- Skeletal deformities e.g. rickets
Acute hypocalcaemia results in:
List at least 4
EXCITABILITY
Bleeding* Anaesthesia* Dysphagia* Convulsions Arrhythmias Tetant Spasms and stridor*
How can you test for hypocalcaemia?
- Chvosteks sign : latent tetany
- Trousseau’s sign: latent tetany
- Di george syndrome
Why can the effects of hypocalcaemia be described as paradoxical?
- HypOcalcaemia leads to membranes becoming MORE excited and less stable
- HypERcalcaemia leads to membranes becomes less excited and more stable
What are the signs and symptoms of hypERcalcaemia?
- Asymptomatic
- Reduced excitability –> constipation, depression
- Abnormal heart rhythms
- Severe hypercalcaemia –> coma, cardiac arrest
