Its worth thinking about just what is going on with bone marrow...

Its worth thinking about just what is going on with bone marrow lesions when you look at them on an MRI. I'll refer to my own MRIs which I discussed in this thread: https://hotcopper.com.au/threads/resolution-of-lumbar-bone-marrow-oedema.6739626/

The BML shows up as a white patch in an MRI:



So what does the white colour mean, microscopically? Well, an MRI is a technique that measures the diffusion coefficient of water, and the water content, at a point in space. That is, its a measurement of how rapidly a water molecule can move throughout a volume from Brownian motion (ie from the jostling of other molecules around it).

That mobility depends on the water molecule's environment. If its boxed in by walls, or locked within the structure of tissue, it can't move very fast. But if its out in some free volume of liquid, it can move around quite quickly. Also, the more water present, the more signal, so the brighter the white.

So the grey and white colours in the MRI are mapping out the tissue density, and porosity, in 3D. White patches are regions that contain more water, and more mobile water.

What this implies is that the bone structure within the lesion is more porous. There is less bone, lower bone density. Its like water occupying the volume within a sponge. This implies a weaker structure, less able to bear load, more likely to fracture under load, and more likely to lead to progression of OA. This is exactly what the study Mozz quotes is saying:

the histology of a BML closely resembles the appearance of a stress fracture or bone non-union. These changes in histology are associated with significant loss of SCB mechanical integrity and inadequate support of the SCBP. Micro CT analysis of tibial plateau retrievals from our laboratory suggest that SCBP fracture may occur as OA progresses

I mean, you can actually see it.

So what does it mean when the white patches disappear, like this:


The water mobility signal from the lesion is suppressed. That means there is less water content, and the water is less mobile, being locked up in tissue or very close to solid boundaries.

In other words, the bone porosity has been filled in. By what? New bone. What the images show is essentially reconstruction of bone within the previously deteriorated structure. It is denser, so almost certainly stronger, and less likely to propagate small fractures under load, or lead to other load bearing damage, and pain.

This is repair, and I find that very exciting. The reason people are finding relief is that damaged bone is being repaired. And this tells you something about what is going on at a lower level. Osteocytes are pumping out bone matrix. Stem cells are migrating from niches within the bone, differentiating into osteocytes, and producing collagen and other materials. The trajectory of the disease is being altered.

It does make me wonder about application of pentosan to other tissue regeneration, like the healing of broken bones, sprains, strains, tendon ruptures, etc. (especially in the elderly), where the same mechanisms are at play. There are many more potential applications to explore.

[As an aside, MRI - magnetic resonance imaging - is one of the coolest physical phenomena there is. Based on the nuclear spin echo effect, discovered by Hahn in 1950 and developed into a diffusion measurement technique by Purcell, who won the 1952 Nobel Prize in Physics for this work. It is exceedingly cunning. Check out the animations of nuclear magnetic decoherence on the wikipedia page: https://en.wikipedia.org/wiki/Spin_echo ]