KNES 363 - BONE REMODELLING DYNAMICS

four types of bone cells that fall into two categories

those that resorb bone or those that form or have formed bone

bone resorbers

closely related to macrophages, cells that migrate throughout all tissues and remove debris and pathological material

bone formers

closely related to cells like fibroblasts, which produce structural molecules in other tissue

osteoclasts

-reabsorb bone

-multinucleated cells formed by the fusion of monocytes originating in bone marrow

-go around and demineralize bone by dissolving the mineral with acids and then release enzymes to break down the collagen

how do osteoclasts move

they move at a rate of tens of microns per day by first demineralizing the bone with acids and dissolving the collagen with enzymes

osteoblasts

-form bone

-mononuclear cells that produce osteoid, the organic portion of the bone matrix

osteoblast rate

-lay down osteoid at a rate of about 1 micron/day

-move 10 times slower than osteoclasts

-DOESN'T MEAN THEY OSTECLASTS REMOVE MORE BONE THAN CAN BE LAID DOWN, its just they can take out faster than we can form, but we can have many formers in one area to make up for it

osteoblasts are differentiated from mesenchymal cells ... how so

mesenchymal stem cells can become an adipose type of cell, cartilage type of cell and in the right type of environment, they can become osteoblasts

osetocytes

-are osteoblasts that have become buried in bone

-they sit in cavities called lacunae and communicate with each other via dendritic processes called canaliculi

-there are about 15,000 lacunae per cubic millimeter of bone

osteocytes - how much blood volume do they occupy

only 1% of BV, but their surface area is huge (1200m2, compared to 3.2m2 for haversian canals, and 9m2 for cancellous bone)

osteocyte function

to orchestrate the bone modelling or remodeling response. They send something and they say yo guys go resorb and form bone, but osteoblasts and osteoclasts can talk to each other as well.

-primary mechanosensors in the bone

how osteocyte form

Osteoblast that has dug itself into a tunnel of bone and new bone has formed around it and becomes and osteocyte

-then grows these dendritic cells form and this is how they communicate with other osteocytes like neurons

-these osteocytes are everywhere and NEED blood supply

-blood volume is very small but because of the dendritic processes their surface area ends up being HUGE

bone lining cell

like osteocytes that have escaped being buried in the bone and become quiescent on the bone surface

Osteoblasts that don't get caught in their own bone matrix, but they are osteoblasts that have done their job and become quiescent and chill on bone surface

-also mechanosensing cells that can orchestrate a response

bone modeling vs remodeling

Modeling - deals with the independent actions of osteoclast and osteoblasts

-forming bone in some areas and removing some bone in other areas

-responsible for large chnages in bone shape and size

-occurs in growth and development

Remodeling - coupled action of osteoclasts and osteoblasts

-work in the same area. Always sequential, osteoclasts first break down and then osteoblasts follow to put down new bone

more osteoblasts vs more osteoclasts

Both modelling and remodelling can both either result in no change in bone volume or can result in increases in bone volume or decrease in bone volume

-just has to do with the relative contribution of osteoblasts vs osteoclast

-more osteoblast = form more, more osteoclast = lose more bone volume

bone modeling

-the INDEPENDENT action of osteoclasts and osteoblasts on different surfaces

-produces changes in bone size and shape (can really impact strength)

-highly active during growth and development and greatly decreases after skeletal maturity

-is highly influenced by physical activity during childhood

bone remodeling

-the SEQUENCIAL, COUPLED action of osteoclast and osteoblasts

-does not usually influence bone size and shape

-can ONLY HAPPEN ON A SURFACE

-it removes a portion of old bone and replaces it with newly formed bone

-occurs throughout life but decreases after growth

-hypothesized to remove bone damage and mechanically "fine tune" the skeleton to best resist load

bone remodeling - mechanically efficient

-mechanically efficient means to extract calcium

Extracting calcium - don't want to make the cross sectional area smaller, so by using the coupled action of remodeling, you don't get rid of the cross sectional area. So they tunnel down in remodeling for cortical bone

trabecular vs cortical bone remodeling

Happens on surface of trabecular bone

In cortical bone you have to make your own surface intracortical so they dig down in those tunnels

-osteoblasts leave behind blood vessels cause the bone needs blood supply

BMUs

Basic Multicellular Units

This is how remodeling is accomplished

-quite consistent - move around 40 microns per day

-this is how osteons are formed

osteoblasts and osteoclasts

Over time if the BMU is in a homeostatic state, it will form as much bone as it removes

-in osteogrosis, you get this increase in osteoclast activity, at the same time get an increase in osteoblast

the A-R-F sequence

BMU remodeling follows a well defined sequence:

1. Activation — differentiation of precursor cells to produce osteoclasts. Time required is about 3 days.

2. Resorption — osteoclasts start to resorb bone at a rate around 40 gm/day. Time is about 30 days.

3.Formation — osteoblasts appear and begin to refill, but leave a vascular loop (Haversian canal) to support metabolism of the BMU and carry nutrients. Time is about 3 months.

*Can take another 6 months to be fully mineralized.

so like 9-10 months total

BMU activation rate vs age for human ribs

You turn over about 5% of cortical bone of your body in this process each year

20% of trabecular turn over each year

-modeling and remodeling very active as children and developping

-slow down eventually

-then around 50 we see this sharp peak in remodeling again, women when they go through menopause and lose estrogen, they start to resorb a bunch of bone estrogen, which inhibits bone remodeling

trabecular bone turnover rates in young adult dogs

look at slide