What is the Ratio Composition of Bone?
1:2:7
water:collagen:hydroxyapatite
Describe the Outer Layer of the Bone
= cortical
made up of osteons of compact bone
Describe an Osteon
- a central haversion canal
- surrounded by concentric rings of matrix = lamellae
- between rings = osteocytes in spaces called lacunae
Describe the Inner Layer of Bone
= cancellous
- trabeculae of spongy bone
What Happens to Bone Under Stress, leading for reasons to Remodel
- bone take stress and strain
- leads to microfractures
- lead to macrofracture
= breakage of the bone
How Does Bone Remodel? Which 2 Hormones are used?
maintaining homeostasis between osteoclast and osteoblast
Osteoclast = dissolve bone
Osteoblast = produce bone
Hormones
- Parathyroid Hormone - increase osteoblasts
- Oestrogen - increase osteoblasts
How do Osteoclasts Activate the Production of Osteoblasts?
- Osteoclast have RANK receptor
- Osteoblasts produce RANK-L and OPG
- RANK-L and OPG activate RANK
- influences differentiation of osteoprotegenitor cells (form of stem cell)
- stimulate and proliferate
- mature into osteoblast
OPG = Osteoprotegerin
What can Negatively Affect Bone Remodeling
tumour factors - dissolve bone
What would Happen if Osteoblasts produced only RANK-L and not OPG?
- would only stimulate osteoclast activation
What is Osteoporosis?
porous weaker bones
- more cancellous bone
- stress is not evenly distributed and so more likely to break
What are the 3 Typical Osteoporotic Fractures?
spinal
- back can become humped - Dowager’s Hump
- posture is stooped and lose height
hip/femur fracture
wrist - collect fracture, when fall on open hand
Which 5 Groups does Osteoporosis Affect?
- post-menopausal women
- elderly
- those with inflam conditions
- those with auto-immunity
- those on long-term corticosteroids
- for rheumatoid arthritis, connective tissue diseases, severe asthma
e.g. prednisolone and hydrocortisone
What must you Incorporate in life to Manage Osteoporosis (5), alongside *drugs (2)?
active
healthy diet
sunlight
no smoking
hormone replacement therapy - oestrogen
*anti-resorptives
*bisphosphonates
- related to pyrophosphate
- used in toothpaste - strengthen enamel
- has a high affinity for bone
What is Hypercalcaemia? Give 2 Effects.
excess calcium entering the blood when bone and hydroxyapatite dissolves
affects the heart, abnormal rhythm and high blood pressure
What are the Symptoms of Hypercalcaemia in Dif Parts of the Body?
brain, gut, kidney
brain - drowsiness, fatigue, cognitive dysfunction, memory loss, coma
gut - nauseous, loss of appetite, constipation, loss of weight
kidney - crystallised stoned, kidney failure, nephrogenic diabetes insipidus
What Is Paget’s Disease of Bone?
an inherited disorder causing an imbalance in the homeostatic mechanisms controlling bone production
Two Phases:
- bone dissolution
- bone laid down - not in correct pattern, weaker
= more prone to fracture, can trap nerves and cause pain
What is the Appearance of Paget’s Disease of Bone on X-ray and Microscope
bone on x-ray is wispy
under microscope - fewer lacunae and fewer osteocytes
What Problems do Paget’s Disease of Bone Cause?
pain and deformities - bone sticks out
What is Osteogenesis Imperfecta?
an inherited disorder where bones aren’t formed properly, easily bend and fracture
related to dentinogenesis imperfecta
What is a Bisphosphonate?
a drug that helps to prevent/slow down bone thinning
Describe the Structure of a Bisphosphonate.
2 pyrophosphates welded together by a carbon
- R1 and R2 molecule from the molecule
= determines the activity and how well it prevents osteoporosis
- R1 is usually hydroxyl group = high affinity for hydroxyapatite
- R2 determines efficacy
*if R2 was nitrogen - can interfere with protein production, mess with cell function, cant prevent apoptosis = die
Give 6 Types of Bisphosphonates, in Descending Order of Efficacy.
Zon’t Ruin A Perfectly Clear Egg
Zoledronate - 10,000
Risedronate - 2,000
Alendronate - 500
Pamidronate - 100
Clodronate - 10
Etidronate - 1
- higher = more protection and inteference with bone resorption
How are Bisphosphonates Administered?
orally or intravenously
What are the Problems with Bisphosphonates? is it Likely?
1)
- due to affinity to bone - stays for a long time
- can interfere with regular cellular process or protein production - apoptosis?
2)
- osteoblast can dissolve bone full of bisphosphonate
- BPP releases around osteoclast
- BPP soak into osteoclast
- = kill
- soak into medium around osteoblast
- = kill
3)
- affect other cells - keratinocytes and fibroblasts
LOL ITS NOT EVEN LIKELY, CAN TAKE A LONG TIME FOR THAT TO HAPPEN
in other words
= reduced activity of clast and blast
= reduced healing ability
= affects other cells
= exposed bone
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Eating Disorders13
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Nutrition and Balanced Diet16
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Inflammation98
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Carbohydrates and Diabetes56
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Lipids37
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Blood and Haemostasis72
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Red Blood Cells33
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White Blood Cells - Leukocytes8
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Respiration29
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Chemiosmosis and ATP Synthase11
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Metabolic Diseases/Disorders3
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Obesity and Diabetes11
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Bone33
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Biology of Cancer51
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Gut Mucosa35
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Metabolism57
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Amino Acid Metabolism19
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Vitamins32
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Minerals - Calcium10
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Decontamination31
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Proteopathic Diseases and Amelogenesis Imperfecta50
