BARCELONA – It is a long held and substantiated belief that osteoarthritis is a biomechanical disease, but evidence is accumulating to support an inflammatory cause. As testament to the strength of both possible causes of the disease, the vote after the World Congress on Osteoarthritis debate, titled "Is OA a mechanical disease or an inflammatory disease?" resulted in a swing from approximately 70/30 in favor of a biomechanical explanation, to 50/50.
Dr. David T. Felson, professor of medicine and public health, and principal investigator of the NIH-funded Boston University Multipurpose Arthritis and Musculoskeletal Diseases Center, argued in favor of OA as a disease of mechanics.
Dr. David T. Felson
In opposition, Dr. Francis Berenbaum, head of the department of rheumatology, Saint-Antoine Hospital, Paris, advanced his case for OA as an inflammatory disease.
Dr. Felson went first, noting that "OA is caused by increased physical forces across a local area of a joint. This is either from abnormal anatomy leading to increased stress with normal load, or excess overall load such as with obesity, or a combination of the two."
The animal models of OA almost all have relied on joint injury and major injury to knees such as meniscal tears, which would support a biomechanical origin for OA. "But diseases are often [the result of] the interplay between different causes," he conceded.
Meniscal tears account for 40%-50% of knee OA, Dr. Felson said, adding: "Multiple studies show surgery to remove tears increases focal stress on the cartilage and causes a high rate of subsequent OA."
Dr. Felson’s argument for abnormal stress as being the cause of OA was further supported when he pointed out that congenital dysplasia increases focal load and markedly increases risk of hip OA at a young age. He also listed various occupations and related sites of OA: for example, cotton workers’ fingers; farmers’ hips and knees; and miners’ knees and spines.
The second major tenet of Dr. Felson’s talk centered on the fact that once OA had developed, pathomechanics overwhelmed all other factors. He described the vicious cycle of joint damage caused by a misaligned knee. "Increased focal stress across one area causes cartilage debris and bone damage." Dr. Felson noted that the inflammation seen in OA is caused by absorption of debris by the synovium, which precipitated more cartilage damage and worsened misalignment.
Dr. Felson supported his point about the role of misalignment worsening OA with data from the Multicenter Osteoarthritis Study (MOST) (Ann. Rheum. Dis. 2012 May 1 [doi: 10.1136/annrheumdis-2011-201070]), which found that 82% of knees with OA had misalignment. Furthermore, he said, "I would contend to you that the genetics of OA is probably predominantly related to abnormally shaped joints. Only 5% of OA is associated with systemic genetics."
Finally, conceding that inflammation was a feature of OA but not a primary cause, Dr. Felson explained its role in the disease. "Inflammation in OA is mostly a consequence of pathomechanics, that is meniscal tears and [anterior cruciate ligament] tears that lead to cytokine release in the synovium and induces joint damage."
If the injury was severe or there were multiple injuries then there was no requirement for inflammatory cytokine release because OA could occur without it, Dr. Felson concluded.
During his presentation, Dr. Berenbaum quoted some renowned names in the field of OA research, and linked them to papers on inflammatory causes of OA. He joked that in light of these papers, his job was nearly done; however he then began to build his expert case for OA as an inflammatory disease.
Approaching the first pillar of his argument from a clinical standpoint, Dr. Berenbaum described the existence of flares in OA that sometimes resembled other inflammatory arthritis. "There’s pain at night, morning stiffness, and swelling."
Focusing on both the macroscopic and histological levels, Dr. Berenbaum added that OA showed evidence of synovitis, featuring different levels of inflammation. "It is a patchy synovitis rather than pannus as in [rheumatoid arthritis], but the degree of inflammation has been shown to be correlated to prognosis, which is more severe when a high degree of synovitis is present," he commented.
This synovitis has been well characterized using MRI and ultrasound, according to Dr. Berenbaum. He addressed the evidence on a tissue and cellular level, by saying that inflammatory and immunologic cells have been seen in the OA synovium. "T-cells, B-cells, and macrophages, which play a role in cartilage degradation, have been shown in a murine experimental model. If macrophages are removed from the synovium in collagenase-induced OA, the cartilage is protected from degradation," explained Dr. Berenbaum.