Biology 466    Unsolved Problems Fall 2010

Regarding bone formation:

(Please think of additions, changes, improvements)

What do we know for sure:

I) Bones are dynamic. All (all? Yes, I think so.) our bones are constantly being broken down by a special kind of multinucleate cell called an osteoclast, and constantly being rebuilt by another special kind of differentiated cell, sometimes called osteocytes, and sometimes called osteoblasts.

II) Rates and amounts of this destruction and re-making are controlled, in part, by hormones (including calcitonin, parathyroid hormone and others, that I would like to find out about, and how their effects differ.)

III) Some mechanism detects mechanical loads on bones, and causes the particular bones bearing the loads to be made stronger (as in the serving arm of tennis players)

IV) When bones are not subject to loads, a net decrease in bone mass occurs
    (which has been a serious problem for astronauts).

V) Bone breakdown is used as a source of calcium, and (I guess) phosphate, analogous to a bank.

VI) Most of our bones are formed by replacement of cartilage. (Except for some flat bones, like the roof of the skull, which form directly from tightly packed collagen fibers.) Cartilage gets destroyed as bone is made in its midst; this is not just a matter of calcification of cartilage (which happens, but is something different)

Sometimes bone gets made in densely-packed collagen, which is normal in the knee-cap, but abnormal in "sesamoid bones" that develop in tendons, and can even happen in the walls of arteries! Marrows with trabeculae sometimes develop within these abnormal bones, so it's more than just a matter of calcium salts getting deposited.

VII) Osteoporosis occurs in older people, and apparently at a higher probability in older women. Osteoporosis is a weakening of bone; and the bones become more brittle.

      Please suggest additions.




Gaps in knowledge about bones and bone formation.

I) When bones detect loads (e.g. in tennis player's arms), is it stress (forces) or strain (% distortion in length, width or shape) that gets detected?

Rate of stress, or rate of strain, might actually be the variables that bones respond to, in the sense of the first derivative with respect to time.

II) Is Piezoelectric voltage the means by which bones detect loads?

III) Is electro-osmotic voltage the means by which bones detect loads?

Maybe people doing experiments weren't aware of the possibility of electro-osmotic voltage, then any voltage they detected would have been assumed to be piezoelectric.

For either piezoelectric or electro-osmotic voltage, in any conductive medium like salty water, voltage will be proportional to the rate of change of strain.

IV) When a heavily loaded bone becomes stronger, is that because the load (or the voltage?) stimulated deposition of bone by osteocytes, or is it because the load inhibited dissolving/digesting of bone by osteoclasts? (a combination is also possible) (And how could we test this experimentally? Mutants could help.)

V) Conversely, when bones get weaker in osteoporosis , is that caused by a decrease in the amount of bone being made by osteocytes, or is it caused by an increase of the amount of bone being dissolved by osteoclasts?

VI) When loaded bones get stronger, do they keep the same ratios of collagen to calcium phosphate? The same question can be asked about osteoporosis, and brittleness would be produced if the percentage of collagen fibers decreased. That's not the only way to produce brittleness, but it's the most evident.

VII) Do the trabeculae in spongy bone degenerate as much or more than the solid surface parts of bones?




Opportunities and medical applications of learning about bone formation.

A) The increased brittleness of bones in older people consists of what?

B) If we lose weight, does bone mass/strength decrease (because of the reduced load)?

C) How are calcium levels changed (if at all) by loads, osteoporosis, or other situations.





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