ADELAIDE, Australia—Vascular pathology may play a role in the pathogenesis or progression of osteoarthritis (OA), according to a review article published in Rheumatology.1 If these findings are confirmed, they may help pave the way toward more targeted, disease-modifying treatments.

"Although cartilage itself is avascular there is reasonable accumulated evidence that vascular problems may underlie the development of osteoarthritis."—David M. Findlay, MD.
"Lack of understanding of the underlying cause(s) for OA mean that treatments remain largely palliative, with joint replacement an option in end-stage disease," writes David M. Findlay, MD, professor of orthopaedic research at the University of Adelaide, in South Australia. "Although cartilage itself is avascular, there is reasonable accumulated evidence that vascular problems may underlie the development of osteoarthritis."

Disruption of subchondral bone blood supply is main suspect

Exactly how vascular pathology affects the OA process is not fully understood, but after gathering the literature, Dr. Findlay suggests that the disruption of the blood flow in the subchondral bone may reduce nutrient diffusion to articular cartilage or that ischemia in the subchondral bone may produce osteocyte death, bone resorption, and articular damage in OA.

"It may be important to recognize these potential aetiological factors in order to develop more effective treatments to inhibit the progression of OA," he concludes.

Dr. Findlay writes that blood flow to the subchondral bone may be reduced by venous occlusion and stasis or by development of microemboli in the subchondral vessels. This results in a compromised nutrient and gas exchange into the articular cartilage, which could initiate degradative changes in the cartilage. In addition, the death of osteocytes in regions of the subchondral bone could trigger osteoclastic resorption of that bone, which could temporarily reduce the bony support for the overlying cartilage.

Further fueling the hypothesis that vascular problems may underlie the development of OA is the finding that many patients with end-stage hip OA tend to have a higher rate of vascular-related comorbidities. Moreover, coagulation abnormalities present in patients with hip osteonecrosis, he writes.

"Since the vasculature in question is that of the subchondral bone, the role of this bone in OA, with its attendant vasculature, cells, and molecular signaling molecules needs to be more intensively considered," he notes. "There is a great deal yet to be learnt about the ways in which the bone and cartilage collaborate in normal bone turnover, and how pathology of the vasculature might affect this."

Are vascular changes the chicken or the egg?

It's hard to say whether the OA disease process starts in the blood vessels or the bone, but constricted blood flow appears to be the cause, explained Kenneth D. Brandt, MD, professor emeritus of medicine and orthopaedic surgery at Indiana University School of Medicine, in Indianapolis.

"The changes in the subchondral bone in OA, including the thickening of trabecular between which the little capillaries run, could be related to abnormal stresses put on the bone. The question is whether vascular abnormalities in bone can cause OA in absence of biomechanics," Dr. Brandt told CIAOMed.

"There is an increasing body of evidence pointing to vascular abnormalities in bone, but it does not point to etiology. Personally, I think it may be an important cause of OA pain," he said. "The bone's effect on circulation through the marrow spaces under the cartilage is happening and whether it would be possible to improve that without improving the mechanics is a big question," he continued. "We are an awful long way from contemplating disease-modifying osteoarthritis drugs (DMOAD) based on vascular pathology."

Reference

1.   Findlay DM. Vascular pathology and osteoarthritis. Rheumatology. 2007; doi:10.1093/rheumatology/kem191 [Epub ahead of print].