I believe due to cytokine storm induced inflammation. IL-1, TNF-a, il6,8 17,18, LIF, OSM, PG(not 2),

Mechanics. Arthritis is a disease of the bone, not cartilage and arthritis (no subchondral hardening, no arthritis) isn't really a disease at all, just the adaptive response to gravity by the biological organism/physical machine through mechanotransduction pathways, which I dont' know but if you i would really like to see?

Dear Hagen

This article may be useful for you.

Ther Adv Musculoskelet Dis. 2013 Apr; 5(2): 77–94. doi:  10.1177/1759720X12467868PMCID: PMC3638313PMID: 23641259

Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations

Jeremy Sokolove📷 and Christin M. Lepus

Regards

Lesions in cartilage come from intrinsic mechanism in which bone and cartilage talk to each other. Lesions do not come from cartilage alone. When cartilage is weak, external mechanical forces make it worst.

Dear Hagen,

Since the 1960s researchers such as Radin (read his papers 1984 and 1973) have shown in animal models that changes in the joint occur primarily in the subchondral bone (SCB; which is highly innervated and vascularised). The changes in the cartilage usually follow the SCB injuries according to these investigators that studied lab animals and my findings in naturally occurring joint injuries of racehorses (see below).

Recently Roemer, Neogi (see below) and others using MRI in human cases also showed that SCB edema lesions (that have been shown by Gonzalez et al to be SCB necrosis) occur prior to changes in the cartilage and are associated with cartilage changes down the track.

Therefore in most types of OA, possibly the problem starts in SCB and then cartilage is involved. If you need the papers mentioned above or further discussion, pleas let me know.

Article Subchondral bone marrow lesions are highly associated with, ...

Article Cartilage Loss Occurs in the Same Subregions as Subchondral ...

Article Prevalence of subchondral bone pathological changes in the d...

Article Role of subchondral bone remodelling in collapse of the arti...

Dear Ebrahim, thanks for your thoughts. There is certainly a close relationship between bone and cartilage, however, this doesn't completely explain the complains:

- often MRI allows diagnosis of subchondral edema, which is not pain-related,

- the same with subchondral bone cysts,

- there are shear injuries, which primarily affect cartilage, not bone, which also can cause pain.

Could you perhaps comment on this and perhaps include mediators and biomechanics in your evaluation?

Dear Hagen, this is a very interesting question which reflects at the old saying about the chicken and the egg. In my humble view according to my understanding biochemistry is the cause of pain at the acute face which though after the cause of damage is leading to the inflammatory markers and biomechanics will follow in chronic phase as other factors as limitation of movements or altered motion is established. The problem is that even at the chronic phase due to the alterations and the abnormality of the joint biochemistry has a role as inflammatory markers are still produced. There is a relatively recent paper explaining mainly the acute part following trauma which I am sure you know about.

“Inflammation in Joint Injury and Post-Traumatic Osteoarthritis” J Lieberthal, N Sambamurthy, and C R. Scanzello, Osteoarthritis Cartilage. 2015; 23(11): 1825–1834.

Hi Hagen,

I address your points in the following:

- often MRI allows diagnosis of subchondral edema, which is not pain-related,

SCB edema lesions detected by MRI are simply tissues with high proton density and nothing else. In other terms increased vacularisation (resorption by osteoclasts) or development of microfractures and haemorrhage/edema would have the same sign of increased proton density in the SCB. Hence “SCB edema lesions” are non-specific terms to describe a variety of causes for focal water accumulation that can be a benign or severely pathologic.

- the same with subchondral bone cysts,

SCB cysts to my limited experience are usually osteoclast filled spaces at the early stages, that later are filled with fibrotic tissue if the bone formation is not successful. We still do not know what causes this repair mechanism to be hindered mid-way, but lack of vscularisation is a good candidate, as endothelium or peri-endothelial cells provide the osteoblast precursors which are supposed to repair bone. For any reason, if the vascularisation is impaired (e.g. due to sclerotic SCB or continuous fragmentation of SCB because of continued heavy loading- I have seen both) the cysts will not be repaired and become permanent. However, if such cysts are under significant loading the peripheral bone fractures and the subchondral bone gives in and the articular surface collapses and pain may ensue. Otherwise, the cysts themselves if not too big, are not the source of pain.

- there are shear injuries, which primarily affect cartilage, not bone, which also can cause pain.

I hope I understood your question.

Honestly, I have not personally seen many such cases. In most of the cases that cartilage had some injuries, the synovial reaction was far more significant to my experience and better correlated with SCB injury that changes in the cartilage. Synovium is well-vascularised and well-innervated tissue that is ignored in many research endeavours.

Chemical induction of OA in animal models also relies on this fallacy too. The acute chemical injected to the joint not only injures cartilage, but also damages the synovium, and induces inflammation, which in many cases is not scrutinised by the naïve researchers focused solely on cartilage.

Could you perhaps comment on this and perhaps include mediators and biomechanics in your evaluation?

Can you please be more specific?

biomechanics is the initial trigger and mediators is the consecutive reactive cascade..