Unsolved Questions About Bone Formation: Sept 10, 2018

You could save tens of thousands of lives (and earn billion$) by inventing a treatment that prevents/inhibits osteoporosis, either by reducing dissolving of bone or by stimulating synthesis of bone.

What do bone cells do that causes bone to form next to the bone cells? ( It isn't secretion , because transmission electron microscopy can see even tiny, thin pieces of bone; but none is seen inside osteocytes.

Possible answers ? Maybe some bone cells secrete high concentrations of calcium ions, and others secrete lots of phosphate very close; enough that multiplying the calcium concentration times the phosphate concentration gives a number that is larger than the "Solubility Product".
By what method could you test for this?

Another possibility: Maybe bone cells secrete a protein ("osteoid") that binds tightly enough to calcium ions and/or phosphate that the solubility product becomes lower (so that the effective solubility of Calcium ions and/or Phosphate is reduced) with the result that calcium phosphate crystals precipitates out of solution.

Other facts to consider: Strontium ions, zirconium ions, plutonium ions also become incorporated into bone (among others). Ions or other chemicals that do this are said to be "bone seeking", although presumably the bone "seeks" the ions.
Large amounts of strontium ion in the diet causes defects in newly made bone.
Animals have also been reported to absorb a higher percentage of strontium ions as compared with the percentage of available calcium ions that they deposit in bone.

Certain antibiotic chemicals also get selectively deposited into bone; and because these also happen to be fluorescent, the have been used by experimenters to map the locations of bone formation. For example, you might put such a chemical in an animal's water every ten days, and later section their bones and study them with a fluorescence microscope, and probably see stripes analogous to tree rings.

Microscopic spheres of lipid membranes have been consistently observed in extracellular fluids very near to where bone is being deposited: But nobody has a good hypothesis about what these membrane spheres could be doing that could cause or increase, or be caused by, deposition of bone.

Bone consists of half type I collagen fiber and half crystals of calcium phosphate. The dentine part of bone is also about 50%-50% collagen The enamel part of teeth is about 95% calcium phosphate crystals and 5% some proteins unrelated to collagen.

Reduced availability of vitamin C prevents secretion of new collagen molecules, which results in net destruction of tendons, dermis, bones and other collagenous tissues, in proportion to the rate of dynamic turnover of each tissue .

Tendons and artery walls sometimes ossify, with abnormal precipitation of calcium phosphate crystals among tightly-packed collagen fibers. Marrow can even form.

To what degree can artificial osteoporosis be caused to occur by reducing amounts of calcium in an animal's food? (Or by increasing amounts of oxalic acid or other substances that chelate (increase solubility) calcium ions.

Ossification of tendons and of tunica media of arteries, especially in the brain

Marrow sometimes develops in ossified walls of arteries

Genetic over-production of calcitonin

"microgravity" - NASA's problem of bone & muscle weakening resulting from weightlessness.

Bone tissue is constantly being made by osteocytes and just as constantly being dissolved and digested by osteoclasts.

Please suggest how you could test experimentally whether osteoporosis results from too much breakdown, or from decreased production of new bone.

There are fluorescent dyes that can "measure" calcium ion concentrations. Certain antibiotics get deposited in newly forming bone, in proportion to how much bone is being formed.


Walter E. Cabrera et al. (1999) Strontium and Bone. [Review paper].
Blackwell Science, Inc. © 1999 American Society for Bone and Mineral Research



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