Bone growth, modelling and remodelling

Question 1

how is bone continuously being formed and turned over?

Answer 1

by modelling and remodelling

Question 2

where does bone modelling mainly take place?

Answer 2

principally in children - in the growing skeleton, where new bone is formed at different sites to those resorbed - net bone formation

Question 3

is there much osteoclastic resorption in bone modelling?

Answer 3

no - little resorption, except change in the shape of the skeleton e.g. shape of long bones, size of vertebrae

Question 4

where is most bone remodelling?

Answer 4

main process in adults

Question 5

is there any change in bone mass in bone remodelling?

Answer 5

no net change, balanced and steady state - bone formation only occurs where bone resorption has previously occurred

Question 6

is there coupling between bone modelling and remodelling

Answer 6

yes - they don’t occur at random

Question 7

why does bone remodelling take place?

Answer 7

• -calcium homeostasis
• -skeletal homeostasis (bone mass)
• normal shaping of bones, increasing dimensions of specific bones, fracture repair

Question 8

explain how remodelling maintains calcium homeostasis?

Answer 8

Ca2+ can be released from bone by osteoclasts, to restore lowered plasma Ca2+ levels, and vice versa
- set by interaction of the three target organs (intestine, kidney and bone) and is controlled mainly by systemic calcium regulating hormones

Question 9

explain how remodelling maintains skeletal homeostasis?

Answer 9

steady state needs to be maintained : resorption = formation

- if resorption is smaller than formation then increase in bone mass if other way round decrease

Question 10

what is a disease where increased bone mass occurs?

Answer 10

osteopetrosis

Question 11

what is a disease where decreased bone mass occurs?

Answer 11

osteoporosis

Question 12

rate of remodelling - trabecular bone

Answer 12

• 20% of the skeletal mass

- yet accounts for 80% of turnover

Question 13

rate of remodelling - cortical bone

Answer 13

• 80% of bone

- only 20% of turnover

Question 14

what is the basic unit of bone turnover?

Answer 14

basic multicellular unit (BMU)

- found in both cortical and trabecular bone

Question 15

remodelling mechanism

Answer 15

Activation- resorption- formation (ARF) sequence

• recruitment / activation of osteoclastic bone resorption
• followed by reversal: recruitment/ activation of osteoblastic bone formation

Question 16

what is the transition between resorption and making of bone referred to as? what is it marked by?

Answer 16

zone of reversal, marked by reversal or cement lines

Question 17

what is the function of the growth plate

Answer 17

important site of bone remodelling - during endochondral bone development where there is an ARF sequence

Question 18

what can altered growth plate development result in?

Answer 18

affect the subsequent bone remodelling in an endochondral bone formation sequence

Question 19

what regulates resorption?

Answer 19

• systemic hormones
• growth factors/ cytokines
• local factors
• nuclear transcription factors (only affects individual cells)

Question 20

how do systemic hormones regulate resorption?

Answer 20

remodelling rate is increased by PTH (parathyroid hormone), T3 (tri-iodothyronine), GH (growth hormone) and VIT D3 and is decreased by CT (calcitonin), oestrogen and glucocorticoids

Question 21

what growth factors/ cytokines regulate resorption

Answer 21

bone morphogenetic proteins

haematopoietic cytokines

Question 22

what growth local factors regulate resorption

Answer 22

prostaglandins

Question 23

mechanical forces in regulation - how does bone accommodate loads that are imposed on them?

Answer 23

undergo alterations in mass, external geometry and microarchitecture

Question 24

mechanical forces in regulation - what do microfractures do?

Answer 24

stimulate remodelling - bone is laid down along lines of maximal compressive or tensile stress (Wolff’s law)
- osteocytes

Question 25

which cells are best suited to respond to forces?

Answer 25

osteocytes

- they are the mechanosensors of the bone -drive the modelling processes

Question 26

how are osteons formed?

Answer 26

• Woven bone is destroyed by osteoclasts in the Howships Lacunae
• Blood vessels then penetrate the gaps as concentric lamellae are formed by osteoblasts which lay down osteoid
• Interstitial Lamellae are remnants of former osteons that have been altered by bone remodelling

Question 27

other bone diseases

Answer 27

Paget'd disease
Periodontal
Chondrodysplasia
Fracture healing
bone tumours
metastases - factors are secreted that turn on uncontrollable osteoclasts