Bone Remodelling

What are the turnover rates in trabecular and cortical bone?

- 30% of trabecular bone is remodelled every year due to the high surface area - 3-5% of cortical bone is remodelled every year

What forms during the bone remodelling of cortical bone?

- A new osteon

What forms during the bone remodelling of trabecular bone?

- A new trabeculae

What is the ARF sequence and where does it occur?

- ARF is the activation resportion formation sequence - Occurs in the BRU

What is the importance of the reversal phase?

- Allows activation of osteoprogenitors for coupling mechanism and production of osteoblasts

Why are blood vessels essential in bone remodelling?

- Blood vessels will form wherever osteoclasts resorb bone - Blood vessels bring osteoprogenitors to reform the bone

What are lining cells?

- Bone lining cells (BLC's) - Cover inactive bone surfaces

Why does bone formation take longer than bone resorption?

- Bone matrix needs to be formed first and then bone needs to be mineralised

What is the difference between bone modelling and bone remodelling?

- Bone modelling affects the size and shape of bone whereas bone remodelling affects the density, mineralisation and and microstructural organisation of bone - Bone modelling takes a long period of time (until reached skeletal maturity: 18 years) whereas bone remodelling occurs over a short period of time (resorption 3 weeks and formation 13 weeks) - Bone modelling doesn't involve bone resorption before bone formation like bone remodelling

What is the bone remodelling unit BRU?

- Bone resorption and formation always occurs in the same place and this is called the bone remodelling unit - Bone resorption is the first step of bone remodelling in the BRU

What hormones regulate bone remodelling?

- Calcium regulating hormones - Most of the receptors for growth factors and hormones are on the osteoblasts 1. Parathyroid hormone (PTH) - Most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid - If you need to release calcium from the bones because you do not have enough blood calcium, PTH stimulates bone resorption - It does this by activating the osteoblast which then releases growth factor to cause bone resorption - Acts through PTH receptor on osteoblasts - Treatment for osteoporosis - High levels and continuous PTH administration is more pro-resorptive - Low levels and intermittent PTH administration is more pro-formative 2. Vitamin D - Vitamin D is also very important in regulating calcium metabolism - Vitamin D increases the activation of osteoclasts - It is also important for the mineralisation of bone because if you do not have vitamin D this can lead to diseases such as rickets. This is where the bones become soft and weak, which can lead to bone deformities due to a deficiency in vitamin D 3. Calcitonin - Does the opposite of PTH as it decreases the activity of osteoclasts - If you have too much calcium, bone resorption needs to be inhibited and this is due to the action of calcitonin - This is one of the few hormones that has receptors on the osteoclasts

How does bone loss occur?

- During bone remodelling, the bone doesn't reform the same quantity of bone that was resorbed

How to avoid bone loss?

- Exercise

How is bone remodelling regulated?

- Hormones - Cytokines - Growth factors - Mechanical environment - Regulation of bone remodelling maintains bone mass

Explain the ARF sequence

Resting - In some BRU's, the bone cells are quiescent and in their resting state. Bone resorption and formation isn't occur. The bone is covered with lining cells Resorption - A signal triggers osteocytes e.g. bone damage - Osteocytes activate osteoclasts to resorb bone in that BRU - Osteoclasts create a hole in the bone - Osteoclasts then move away Reversal - Transition between resorption and formation - Signalling molecules in the BRU send signals to osteoblasts to fill this part of the bone Formation - Osteoblasts form the same amount of bone that was resorbed

Bone remodelling is said to be asynchronous. What does this mean?

- In one location there will be resorption, in another location it will be quiescent and in another location there will be bone remodelling - Resorption always takes place first - New bone will then form where osteoclasts have removed bone

Why are women going through the menopause more likely to develop osteoporosis?

- Loss of oestrogen

How are micro fractures detected by osteocytes?

- Mechanosensing - Fatigue damage and microcracks induce osteocyte apoptosis at the microcracks - When the osteocytes die by apoptosis, they release signals which activate osteoclasts and osteoblasts at the bone surface

What is bone remodelling balance?

- More formation than resorption = growth - Formation is equal to resorption = steady state 20-40 years old - More resorption than formation = bone loss (osteoporosis)

How does oestrogen have a positive effect on bone?

- Oestrogen stimulates osteoblasts to form new bone and it inhibits osteoclasts to resorb bone - Acts through its receptors, ERa and ERb - It prolongs the life of osteoblasts - Promotes osteoclast apoptosis - Oestrogen has receptors on both osteoblasts and osteoclasts - Stimulates osteoblast proliferation, differentiation and increased deposition and mineralization of matrix

How is cortical bone remodelled?

- Osteoclasts resorb the cortical bone creating a tunnel - Osteoblasts then follow the osteoclasts reforming the bone

How does the coupling mechanism work?

- Research suggests that osteoclasts and osteoblasts communicate with each other via signalling molecules e.g. ephrin B ligands and receptors - HOWEVER, sometimes the osteoclasts have left before the osteoblasts arrive. Other research suggests that the osteoclasts leave a signal at the resorbed bone for the osteoblasts e.g. growth factors are released which tell the osteoblasts how much bone is resorbed and how much bone to then reform

How is trabecular bone remodelled?

- Takes place on the surface of trabecular bone - Osteoclasts resorb bone on the surface - Osteoblasts reform the bone making a flat surface

What is the coupling mechanism and when does it occur?

- The osteoclasts signal to the osteoblasts how much bone that was there before to reform the same quantity - Occurs in the reversal phase

What are the reasons for remodelling of the bone?

- To release calcium from the skeleton - To generate the optimum architecture for mechanical usage - Maintenance - Damage (macro/micro fractures) - Pathological

Why is more bone lost in the trabecular compartment than in the cortical bone?

- Trabecular compartment has a faster turnover rate - More bone is therefore lost

What bone is metabolically active?

- Trabecular/spongy