Bone remodelling Flashcards
What is bone modelling and re-modelling in early childhood?
Modelling = formation + shaping Re-modelling = replacing + renewing
What is bone modelling and re-modelling in adulthood?
Modelling = during a fracture Re-modelling = maintaining skeletal integrity
What is the purpose of bone remodelling?
- Release Ca2+ from the skeleton
- Generate optimum architecture for mechanical usage
- Maintenance (failure prevention)
- Damage (macro/micro fractures)
- Pathological
- Collaborative and sequential effort of a group of cells (BRU)
What is the bone remodelling site?
Cyclic and occurs in many parts of the bone
ARF sequence, activation, resorption, formation
Resorption: 2-4 weeks
Formation: 4 months
- more remodelling sites in trabecular bone because surface area is bigger
- in order for osteoblasts to be active, recruitment of osteoclast progenitors must take place
- reabsorption ends with osteoclast apoptosis
What happens in the reversal phase at the BRU?
Lacunae is populated by monocytes, osteocytes that are liberated by bone reabsorption but also osteoblast progenitors
What happens in the formation phase at the BRU?
Osteoblasts will deposit bone in three cavities = complete renewal of bone, when osteoblasts are finished 70% die by apoptosis, remaining = lining cells or are incorporated into the bone matrix to become osteocytes
What are the turnover rates of trabecular bone?
High surface area on which bone destruction and rebuilding occurs
- remodelling occurs at a rate of 30% every year
What are the turnover rates of cortical bone?
Haversian lacunae are sites of cortical bone remodelling
- remodelling occurs at a rate of 3-5% every year
- adult human cortical bone is replaced approx. every 15 years therefore the effects of remodelling imbalance appear even sooner in skeletal sites with a high proportion of trabecular bone (vertebral bodies)
Describe bone remodelling activity in cortical bone
Osteoclasts have to dig out a tunnel creating a cutting cone
- with new bone formed in the closing cone
What is the Haversian system?
Net result of remodelling cycle in cortical bone is production of a new osteon
Describe bone remodelling activity in trabecular bone
- Osteoclastic reabsorption
- Reversal
- Preosteoblastic migration
- Osteoblastic matrix formation
- Mineralisation
What is the net result of a remodelling cycle in trabecular bone?
Production of a new trabeculae = osteon
What role does vasculature play in bone remodelling?
Bone vessel is the centre of the bone remodelling unit
- role in osteoprogenitor migration
How is bone modelling activated?
Can be random
Proportion is targeted towards specific sites that need to be repaired
- fatigue damage
- microcracks affect mechanosensing
How does damage to osteocytes act as a stimulus for bone reabsorption?
Fatigue damage and micro-cracks induce osteocyte apoptosis and these apoptotic osteocytes actively produce Rank Ligand (cytokine which promotes bone reabsorption)
Viable osteocytes are necessary to prevent osteoclast activation and maintain bone mass which produce osteoprotegrin (anti-apoptotic signal), directs bone remodelling to the site of damage
How do osteocytes direct bone remodelling?
Increase the number of reabsorption cavities, found in an overloaded limb, was spatially related to the site of micro-damage
What are coupling mechanisms in bone remodelling?
- Resorption preceds bone formation
- Coupling occurs during the reversal phase
- balance after remodelling cycle should be neutral
- Stimulation of osteoblast activity in response to reabsorption is termed coupling
What is the nature of the coupling signal?
- Direct contact and bi-directional signalling via ephrin π ligands and receptors
- Release of growth factors from matrix by osteoclast action
- Gradient of strain, osteoclasts being activated in response to reduced strain and osteoblasts in response to increased strain
- Acidification of the reabsorption compartment
What is the reversal phase?
Coupling depends on availability of osteoprogenitors
Lengthen of reversal phase has been debated
- important for the activation of osteoprogenitors
What is the bone remodelling balance?
Formation > resorption = growth
Formation = resorption - steady state (20-40 years)
Formation < resorption = bone loss (osteoporosis)
What factors regulate bone resorption?
Hormones
Cytokines
What factors regulate bone formation?
Growth factors
Mechanical environment
What is the significance of the ParaThyroid hormone (PTH)?
Treatment for osteoporosis
- most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid
- acts through PTH receptors on osteoblasts
- intermittent PTH administration is more pro-resorptive
- continuous PTH is more pro-formative
What is the significance of 1,25-dihydroxyvitamin D?
Increases osteoclast recruitment/activity
- required for normal matrix mineralisation
- deficiency = osteomalacia, rickets
What is the significance of the Calcitonin hormone?
Decreases osteoclast recruitment/activity
- emergency hormone, not much effect in normal adults
What role does estrogen play in bone maintenance?
Exerts critical (long term) beneficial effects on bone maintenance
- has important effects on bones in both males and females
- acts through receptors ERπ and ERπ
- known to effect both osteoclasts and osteoblasts
- promotes osteoclastic apoptosis
- stimulates osteoblast proliferation, differentiation and increased deposition and mineralisation of matrix
- loss of estrogen (postmenopause/ovariectomy) results in osteoporosis
What are local factors in bone remodelling and what effect do they have?
- Wnt glycoproteins: the Wntπ catenin pathway is osteogenic
- sclerostin is a negative modulator of this pathway - antagonist - Cytokines: normal products of immune cells and bone cells e.g. IL, tumour necrosis factor (TNF), RANK ligand, colony - stimulating factors
How is bone remodelling controlled by mechanical regulation?
Disuse
- β
Bone mass
+ β
Mechanical loading
- mechanical loading - strain = deformation
- inc. growth (osteoblasts make more bone)
no loading e.g. space or bed = bone loss
Bone has to be strong enough to withstand loading within reason
How does age cause changes in remodelling?
Decline in bone formation as it is only needed to repair microdamages
Negative balances between volumes of bone reabsorbed and formed during remodelling, inc rate of bone remodelling
Decline in periosteal bone formation, insufficient to compensate vigorous endosteal bone loss
What is a reversible deficit in bone volume?
Osteoclasts excavate resorption cavity and a reversal phase, osteoblast deposit osteoid - undergo primary mineralisation. In young adulthood, completely reversible because cavity completely filled with matrix
What is a irreversible deficit in bone volume?
Remodelling imbalance occurs, cavity not completely filled
What is osteoporosis?
Systemic skeletal disorder characterised by low bone mass and micro architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
