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What are the 7 key functions of bones?

- Storage of minerals (e.g. calcium)

- Transmission of body weight

- Protection of vital organs and structures

- Anchorage - lever system for movement

- Determination of body shape

- Raises body from ground against gravity

- Houses bone marrow to facilitate haematopoeisis


What are the two skeletons?

- Appendicular (126 bones) = green one

- Axial (80 bones) = white one


What are the five types of bone classification by shape?

- Long bones = tubular shape with hollow shaft and ends expanded for articulation, e.g. femur

- Short bones = cuboidal in shape, e.g. carpal bones

- Flat bones = plates of bones, often curved, protective function, e.g. sternum

- Irregular bones = shapes vary, often specific to function, e.g. mandible

- Sesamoid bones = round, contain nodules for tendon attachment, e.g. patella


What are the two types of bone structure macroscopically?

- Cortical/compact = dense, solid, incorporates spaces for blood vessels and cells

- Trabecular/spongy = formed from a network of struts (trabeculae), spongy appearance, many spaces filled with bone marrow


What are the two types of bone classification microscopically?

- Primary/woven = made quickly, disorganised, no clear structure 

- Secondary/lamellar = made slower, organised, clearly structured 


How does the bone structure contribute to function?

- Hollow long bone = keeps mass away from neutral axis, minimises deformation

- Trabecular bone = gives structural support while minimising mass

- Wide ends = spreads load over weak, low friction surface 

- Flat bones = protective 


What is bone composed of? 

- 50-70% mineral (mainly hydroxyapatite)

- 20-40% organic matrix = collagen (type 1) is 90%, non-collagenous proteins = 10%

- 5-10% water


What are the cells of the bone?

- Osteoclasts = multinucleated

- Osteoblasts = plump, cuboidal

- Osteocytes = stellate, entombed in bone

- Bone lining cell = flattened, lining the bone


What is the origin of osteoblasts?

Mesenchymal stem cells


What do osteoblasts do? 

- Blast = build, so form bone in the form of osteoid

- Produce type 1 collagen

- Make non-collagenous proteins

- Secrete factors that regulate osteoclasts


What are osteoclasts formed from? 

Haematopoeitic stem cells


What are the functions of osteoclasts?

- Resorb bone

- Dissolve the mineralised matrix

- Break down collagen in the bone 


What is the difference between bone modelling and bone remodelling?

- Bone modelling = gross shape is altered, bone added or taken away

- Bone remodelling = all the bone is altered, new bone replaces old bone 


Why does bone remodelling occur?

- Forming bone shape

- Replacing woven bone with lamellae

- Reorientation of fibrils and trabeculae to reinforce mechanical strength 

- Response to load

- Calcium release

- Damage repair


What are the 5 steps of bone remodelling?

- Activation = monocytes on bone surface differentiate to become osteoclasts

- Reabsorption = osteoclasts secrete acid to dissolve the bone mineral

- Reversal = osteoblasts are stimulated/recruited

- Formation = osteoblasts secrete osteoid to form bone matrix

- Quiescence = without stimulation there is no action


How many amino acids does one collagen fibre contain? What is every third amino acid?

- One collagen fibre = around 1000 amino acids

- Every third amino acid is glycine


What are the stages of collagen synthesis?

- 3 collagen models come together to form a triple helix called tropocollagen

- It is secreted from a fibroblast, here its polypeptides are removed

- Tropocollagen molecules then form covalent cross links between one molecule's lysine and another's hydrolysine - this process forms microfibrils

- Microfibrils combine forming fibrils

- Fibrils combine to form fibres

- Fibres form fascicles which are enclosed in endotendon

- The tendon is enclosed in the epitendon


Which bonds join collagen together?

- Covalent cross-links = within and between tropocollagen

- Hydrogen bonds = between hydroxyproline molecules, within tropocollagen

- Between the tropocollagen molecules 


What is collagen broken down by?

 Enzymes called proteinases, especially collegenases and cathepsin K



What is the process of bone formation known as? What are the two main types?

- Ossification

- Endochondral = bone forms from a hyaline cartilage precursor, occurs during foetal development, long bone formation, and fracture healing

- Intermembranous = bone forms directly from mesenchyme, occurs during foetal development to form flat and irregular bones


What happens in endochondral ossification?

- Chondrocytes produce a cartilaginous precursor

- Primary ossification centre is formed as osteoblasts lay bone onto the cartilage

- Osteoclasts break down the cartilage

- POC is vascularised as blood vessels invade

- Periosteum collar is formed outside the bone as perichondrium is broken down

- Parts of the spongy bone making up the POC are broken down to form the medullary cavity

- Process repeats at ends of long bones to form the secondary ossification centre

- Some layers of cartilage remain between SOC and POC, known as the epiphyseal (growth) plate


What happens in intermembranous ossification?

- Mesenchymal stem cells replicate, forming clusters called nidus

- Stem cells in nidus become osteoprogenitor cells

- Osteoprogenitor cells differentiate into osteoblasts

- Osteoblasts produces extracellular matrix containing T1 collagen fibres 

- Some osteoblasts become trapped in matrix, forming osteocytes

- Bond spicules form via mineralisation 

- Spicules grow and fuse to form trabeculae, around which periosteum is now formed


What does the epiphyseal plate allow? What does the size of the growth plate increase with?

- Epiphyseal (growth) plate = allows continued growth of long bones in childhood and adolescence

- Size of growth plate increases with constant chondrocyte division

- Some chondrocytes simultaneously degenerate - they are then ossified by osteoblasts

- This process continues throughout growth, after puberty the epiphyseal plate is completely ossified (fused) and growth ceases


What are the 3 general aspects of bone growth?

- Mineralisation = hydroxyapatate crystals being deposited into the bone fibrous matrix, hardens bone, vitamin D and PTH mediated

- Modelling = occurs during growth, osteoblasts building and osteoclasts breaking down to form overall shape

- Remodelling = occurs after growth, alteration and replacement of old bone with new, occurs via blast and clast activity similar to modelling 


What stimulates PTH (parathyroid hormone) secretion? What does PTH do?

- Decreased serum calcium results in increased PTH secretion

- PTH increases bone remodelling rates and calcium RESORPTION

- Presence of PTH leads to the conversion of 25-hydroxyvitamin D (calcidiol) to the active 1,25-dihydroxyvitamin D (calcitriol = active vitamin D)

- Combined effect leads to an increase in serum Ca2+ levels


Can Vitamin D be directly consumed? What does active vitamin D cause?

- Vitamin D cannot be directly consumed, and we don't actually absorb it from the sun

- Active vitamin D increases calcium absorption and is fundamental in maintaining bone mineral density


How is vitamin D synthesised? 

- 7-dehydroxycholesterol is synthesised directly from ingested cholesterol 

- This is converted to Vitamin D3, facilitated by UVB radiation from the sun

- Vitamin D3 is converted to 25-hydroxyvitamin D (CALCIDIOL) in the liver, via the cytochrome p450 system

- Calcidiol is converted to 1-25-dihydroxyvitamin D (CALCITRIOL) in the presence of PTH

- The presence of calcitriol can then go on and promote gut calcium ion absorption


What is calcitonin produced by? What is its function?

- Calcitonin is produced by C cells (parafollicular cells) in the thyroid gland

- Action not really known, however is secreted in response to serum calcium ion increase, so it is potentially involved in the negative feedback mechanism to reduce bone reabsorption


Where is dietary calcium sourced from? How is extracellular calcium accumulated? How is extracellular calcium used?

- Dietary calcium sources included dairy, vegetables, and oily fish

- Extracellular calcium accumulated via bone resorption, reabsorption in the kidney or absorption in the small intestine

- Extracellular calcium used in bone deposition, kidney filtration and secretion in the small intestine


Draw out calcium homeostasis.